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COVID-19 Pandemic stress affected ovulation, not menstruation
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ENDO 2022
Osteoporosis risk rises with air pollution levels
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.
The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.
The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.
In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m3 for PM2.5 and 25.0 mcg/m3 for PM10.
“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.
Data on more than 59,000 Italian women
Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.
For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).
The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.
Both thresholds of PM10 > 30 mcg/m3 and PM2.5 > 25 mcg/m3 “are considered safe … by the World Health Organization,” Dr. Adami pointed out.
“If you live in a place where the chronic exposure is less than 30 mcg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.
“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.
One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.
Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.
Does air pollution have an immunologic effect?
In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.
“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.
“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.
The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.
A version of this article first appeared on Medscape.com.
AT THE EULAR 2022 CONGRESS
Could a type 2 diabetes drug tackle kidney stones?
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
than patients who received placebo during a median 1.5 years of treatment.
These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.
Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.
The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.
Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.
Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.
However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.
Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.
This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
‘Provocative’ earlier findings
The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.
Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.”
Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.
They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.
These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
Pooled data from 20 trials
The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.
Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).
The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.
During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.
This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.
The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.
When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.
This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.
The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
Upcoming small RCT in adults without diabetes
Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”
“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.
There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.
A new trial should shed further light on this.
Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.
This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.
The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022
This breast tumor subtype disproportionately affects Black women
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
That finding, suggested by transcriptomic analyses of a racially diverse cohort that identified racial disparities in the proportion of HR-positive basal tumors, underscores a need for diverse racial representation in clinical trials, researchers recently reported at the annual meeting of the American Society of Clinical Oncology.
The leading cause of cancer-associated death among Black women is breast cancer, and compared with White women, Black women are 41% more likely to die from breast cancer, said Sonya A. Reid, MD, MPH, a medical oncologist with the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and the study author.
Few studies, Dr. Reid said, have evaluated if tumor biology differences contribute to the racial outcome disparity. Hormone receptor-positive tumors classified as basal-type with Blueprint genomic analysis (HR+/Basal) are overrepresented among Black women. These tumors are thought to be similar to triple negative breast cancer tumors (TNBC) which are more aggressive and tend to have worse outcomes.
TNBC, Dr. Reid said, is associated with low ACKR1 expression, which encodes the Duffy antigen and correlates with worse breast cancer outcomes. Given the overrepresentation and worse outcomes among Black women with HR-positive basal tumors, Dr. Reid and colleagues compared differentially expressed genes (DEGs) by race and subtype.
Their analysis of data from 2,657 women with stage 1, 2, and 3 breast cancer, showed that among 455 Black women, 315 had luminal (HR-positive luminal) and 140 had basal tumors (66 HR-positive basal and 74 HR-negative basal). Among White women included as a reference group (n = 2,202), tumors were were HR-positive luminal in 1,825 and HR-positive basal or HR-negative basal in 158 and 219, respectively. The proportion of Black women with HR-positive basal tumors was significantly higher, compared with White women (15% versus 7%; P <0.001) as was the proportion of Black women with HR-negative basal tumors, compared with White women (16% versus 10%; P <0.001).
Women included in the study were participants in the ongoing BEST study (5R01CA204819) at Vanderbilt University Medical Center, Nashvlile, Tenn., or FLEX study (NCT03053193). In a multidimensional scaling analysis, HR-positive basal tumors clustered with TNBC rather than with HR-positive luminal tumors. While a differential gene expression analysis comparing HR-positive basal with HR-positive luminal tumors resulted in over 700 differently expressed genes in Black women, no such genes were identified when comparing HR-positive basal tumors with TNBC. ACKR1 expression in HR-positive basal tumors was comparable to TNBC in Black women (P = 0.81) and White women (P = 0.46). In contrast, HR-positive basal tumors had significantly lower ACKR1 expression than HR-positive luminal tumors in Black (P < 0.01) and White women (P < 0.01).
The findings highlight the importance of further genomic classification for patients with HR-positive tumors, Dr. Reid said.
“Molecular subtype classification is not standard of care for patients with localized breast cancer. However, the current analysis suggests that genomic classification could have important clinical implications. Women with HR-positive basal tumors should not be treated uniformly with HR-poisitive luminal tumors. Our data suggest that HR-positive basal tumors are transcriptomically similar to TNBC tumors and should potentially be treated similar to TNBC,” she said.
There are several genomic tests that are widely available clinically to guide treatment decisions and are covered by insurance, Dr. Reid said. Prior studies have shown racial disparity in the omission of genomic tests to guide treatment decisions, however. “Increasing access [to] and awareness of genomic testing will improve guideline-adherent care for all patients. We must intentionally recruit minority patients into clinical trials, knowing that Black women are more likely to die of their breast cancer,” she said.
A further impediment lies in the fact that while most minority patients receive their care in the community, most clinical trials are offered at large academic centers, Dr. Reid said. Future trials, she urged, should include a predetermined percentage of racial/ethnic groups in the clinical trial design to reflect the breast cancer population.
Limitations of the study included that race was self-reported. She noted further that the data for survival are not yet mature. She added, “We will also be evaluating the association of different systemic treatment options across the different molecular subtypes.”
Dr. Reid reported no relevant disclosures.
FROM ASCO 2022
Venetoclax combos prolong progression-free CLL survival
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EHA 2022
Precision medicine vs. antibiotic resistance
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Metastatic lobular, ductal cancers respond similarly
CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.
between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.
“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.
The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.
The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.
The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.
A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.
Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.
So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.
Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.
There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.
The study received no external funding.
CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.
between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.
“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.
The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.
The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.
The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.
A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.
Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.
So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.
Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.
There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.
The study received no external funding.
CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.
between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.
“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.
The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.
The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.
The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.
A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.
Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.
So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.
Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.
There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.
The study received no external funding.
AT ASCO 2022
Survival for elderly breast cancer patients 25% after 4 years
in actual clinical practice than younger counterparts.
After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.
For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.
The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).
Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.
“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.
According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.
Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.
“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.
While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.
“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.
in actual clinical practice than younger counterparts.
After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.
For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.
The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).
Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.
“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.
According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.
Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.
“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.
While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.
“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.
in actual clinical practice than younger counterparts.
After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.
For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.
The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).
Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.
“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.
According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.
Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.
“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.
While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.
“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.
FROM ASCO 2022
‘Large benefit’ in ovarian function suppression for breast cancer
“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.
The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.
Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.
Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).
The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”
A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.
“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.
The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.
Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.
Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).
The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”
A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.
“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.
The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.
Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.
Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).
The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”
A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.
FROM ASCO 2022
Neighborhood analysis links breast cancer outcomes to socioeconomic status
A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.
“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.
She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.
In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.
The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).
It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.
The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).
Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).
The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.
Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.
“We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.
Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.
A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.
“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.
She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.
In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.
The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).
It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.
The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).
Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).
The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.
Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.
“We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.
Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.
A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.
“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.
She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.
In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.
The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).
It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.
The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).
Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).
The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.
Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.
“We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.
Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.
FROM ASCO 2022