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Metabolic syndrome skews Oncotype DX reliability
SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.
This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.
Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.
Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.
In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.
The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.
During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.
Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."
Dr. Lakhani reported having no financial conflicts.
SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.
This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.
Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.
Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.
In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.
The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.
During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.
Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."
Dr. Lakhani reported having no financial conflicts.
SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.
This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.
Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.
Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.
In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.
The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.
During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.
Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."
Dr. Lakhani reported having no financial conflicts.
AT THE ANNUAL SAN ANTONIO BREAST CANCER SYMPOSIUM
Major Finding: Of 322 patients with low-risk early-stage breast cancer, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 of the patients; 13 (62%) of them had metabolic syndrome.
Data Source: A single-center observational study of women newly diagnosed with estrogen receptor–positive/lymph node–negative breast cancer. Patients’ tumors were analyzed using the Oncotype DX assay.
Disclosures: Dr. Lakhani reported having no financial conflicts.
Cancer deaths declined 20% since 1991
Cancer deaths have declined 20% since 1991, which means there were 1.2 million fewer deaths from cancer in 2009, according to the American Cancer Society.
The overall cancer death rate decreased from 215 per 100,000 in 1991 to 173 per 100,000 in 2009. Death rates declined more sharply for cancers of the lung and prostate in men, for breast cancers in women, and for colon and rectal cancers for men and women. The ACS attributes the drops to decreases in smoking and improvements in early detection and treatment.
The most common causes of cancer death in Americans, accounting for 50% of cancer deaths, are cancers of the lung and bronchus, prostate, and colorectum in men; and cancers of the lung and bronchus, breast, and colorectum in women. This year, there will be 1.6 million cancer cases and 580,350 cancer deaths; lung cancers will account for 25% of cancer deaths in men and women this year, according to estimates from the ACS.
The mortality figures and incidence data are contained in two reports: Cancer Facts & Figures 2013 and Cancer Statistics 2013, both published in CA: A Cancer Journal for Clinicians. (doi:10.3322/caac.21166). The reports were published online on Jan. 18.
Incidence rates are on the decline for most cancers with the exception of melanoma, and liver, thyroid and pancreatic cancer.
Dr. Daniel M. Siegel, president of the American Academy of Dermatology, said in a statement that a rising incidence of melanoma "is particularly concerning because skin cancer can often be easily prevented and detected." Dr. Siegel said that the AAD and its members "are actively working to reduce the incidence of skin cancer and change society’s attitudes and behaviors toward sun exposure and tanning."
Death rates from pancreatic cancer have increased over the last decade, due to what the ACS called "a lack progress in primary prevention, early diagnosis, and treatment of this cancer." The ACS report included a special section devoted to updated information on the occurrence and treatment of pancreatic cancer. Most patients with pancreatic cancer die within a year of diagnosis; the 5-year survival rate is 6%.
The ACS also noted that the disparity in cancer outcomes based on ethnicity and income, "particularly [among] those diagnosed with colorectal or breast cancer where earlier detection and better treatments are credited for the improving trends," said John R. Seffrin, Ph.D., chief executive officer of the ACS, in a statement. "We can and must close this gap so that people are not punished for having the misfortune of being born poor and disadvantaged."
The 5-year survival rate in 2002-2008 for white women with breast cancer, for instance, was 92%, whereas for black women, it was 78%. For colon cancer, the 5-year survival rate was 66% for whites, but 55% for blacks.
On Twitter @aliciaault
Cancer deaths have declined 20% since 1991, which means there were 1.2 million fewer deaths from cancer in 2009, according to the American Cancer Society.
The overall cancer death rate decreased from 215 per 100,000 in 1991 to 173 per 100,000 in 2009. Death rates declined more sharply for cancers of the lung and prostate in men, for breast cancers in women, and for colon and rectal cancers for men and women. The ACS attributes the drops to decreases in smoking and improvements in early detection and treatment.
The most common causes of cancer death in Americans, accounting for 50% of cancer deaths, are cancers of the lung and bronchus, prostate, and colorectum in men; and cancers of the lung and bronchus, breast, and colorectum in women. This year, there will be 1.6 million cancer cases and 580,350 cancer deaths; lung cancers will account for 25% of cancer deaths in men and women this year, according to estimates from the ACS.
The mortality figures and incidence data are contained in two reports: Cancer Facts & Figures 2013 and Cancer Statistics 2013, both published in CA: A Cancer Journal for Clinicians. (doi:10.3322/caac.21166). The reports were published online on Jan. 18.
Incidence rates are on the decline for most cancers with the exception of melanoma, and liver, thyroid and pancreatic cancer.
Dr. Daniel M. Siegel, president of the American Academy of Dermatology, said in a statement that a rising incidence of melanoma "is particularly concerning because skin cancer can often be easily prevented and detected." Dr. Siegel said that the AAD and its members "are actively working to reduce the incidence of skin cancer and change society’s attitudes and behaviors toward sun exposure and tanning."
Death rates from pancreatic cancer have increased over the last decade, due to what the ACS called "a lack progress in primary prevention, early diagnosis, and treatment of this cancer." The ACS report included a special section devoted to updated information on the occurrence and treatment of pancreatic cancer. Most patients with pancreatic cancer die within a year of diagnosis; the 5-year survival rate is 6%.
The ACS also noted that the disparity in cancer outcomes based on ethnicity and income, "particularly [among] those diagnosed with colorectal or breast cancer where earlier detection and better treatments are credited for the improving trends," said John R. Seffrin, Ph.D., chief executive officer of the ACS, in a statement. "We can and must close this gap so that people are not punished for having the misfortune of being born poor and disadvantaged."
The 5-year survival rate in 2002-2008 for white women with breast cancer, for instance, was 92%, whereas for black women, it was 78%. For colon cancer, the 5-year survival rate was 66% for whites, but 55% for blacks.
On Twitter @aliciaault
Cancer deaths have declined 20% since 1991, which means there were 1.2 million fewer deaths from cancer in 2009, according to the American Cancer Society.
The overall cancer death rate decreased from 215 per 100,000 in 1991 to 173 per 100,000 in 2009. Death rates declined more sharply for cancers of the lung and prostate in men, for breast cancers in women, and for colon and rectal cancers for men and women. The ACS attributes the drops to decreases in smoking and improvements in early detection and treatment.
The most common causes of cancer death in Americans, accounting for 50% of cancer deaths, are cancers of the lung and bronchus, prostate, and colorectum in men; and cancers of the lung and bronchus, breast, and colorectum in women. This year, there will be 1.6 million cancer cases and 580,350 cancer deaths; lung cancers will account for 25% of cancer deaths in men and women this year, according to estimates from the ACS.
The mortality figures and incidence data are contained in two reports: Cancer Facts & Figures 2013 and Cancer Statistics 2013, both published in CA: A Cancer Journal for Clinicians. (doi:10.3322/caac.21166). The reports were published online on Jan. 18.
Incidence rates are on the decline for most cancers with the exception of melanoma, and liver, thyroid and pancreatic cancer.
Dr. Daniel M. Siegel, president of the American Academy of Dermatology, said in a statement that a rising incidence of melanoma "is particularly concerning because skin cancer can often be easily prevented and detected." Dr. Siegel said that the AAD and its members "are actively working to reduce the incidence of skin cancer and change society’s attitudes and behaviors toward sun exposure and tanning."
Death rates from pancreatic cancer have increased over the last decade, due to what the ACS called "a lack progress in primary prevention, early diagnosis, and treatment of this cancer." The ACS report included a special section devoted to updated information on the occurrence and treatment of pancreatic cancer. Most patients with pancreatic cancer die within a year of diagnosis; the 5-year survival rate is 6%.
The ACS also noted that the disparity in cancer outcomes based on ethnicity and income, "particularly [among] those diagnosed with colorectal or breast cancer where earlier detection and better treatments are credited for the improving trends," said John R. Seffrin, Ph.D., chief executive officer of the ACS, in a statement. "We can and must close this gap so that people are not punished for having the misfortune of being born poor and disadvantaged."
The 5-year survival rate in 2002-2008 for white women with breast cancer, for instance, was 92%, whereas for black women, it was 78%. For colon cancer, the 5-year survival rate was 66% for whites, but 55% for blacks.
On Twitter @aliciaault
FROM CA: A CANCER JOURNAL FOR CLINICIANS
Score helps predict late distant metastases in ER-positive breast cancer
A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.
Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.
Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.
Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.
And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.
"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.
"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."
Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.
"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."
Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.
"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."
"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.
"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."
Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."
EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.
The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.
"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.
A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.
Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.
"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.
When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.
However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.
Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.
"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.
In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.
Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.
A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.
Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.
Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.
Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.
And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.
"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.
"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."
Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.
"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."
Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.
"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."
"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.
"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."
Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."
EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.
The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.
"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.
A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.
Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.
"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.
When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.
However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.
Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.
"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.
In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.
Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.
A new multigene score called EndoPredict improves on clinical measures for predicting whether estrogen receptor–positive breast cancer will metastasize, especially in the long term. The score therefore may help identify patients who can skip extended antihormonal therapy.
Investigators with the Austrian Breast and Colorectal Cancer Study Group (ABCSG) studied more than 1,700 postmenopausal patients with early estrogen receptor (ER)-positive, HER2-negative breast cancer who underwent surgery and received hormonal therapy for 5 years.
Using formalin-fixed, paraffin-embedded tumor tissue, the team derived a pretreatment EndoPredict score (Sividon Diagnostics) for each patient. The score reflects expression levels of 12 genes involved in proliferation, ER signaling, and differentiation.
Patients with a low vs. high EndoPredict score were 20%-30% more likely to be free of distant metastases during the first 5 years of follow-up and also thereafter, lead investigator Dr. Peter Dubsky reported at the San Antonio Breast Cancer Symposium.
And an EndoPredict clinical score, which combined the score with clinical features, showed even better prediction, especially in the long term: Patients having a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to remain free of distant metastases thereafter. In absolute terms, more than 98% of this low-risk group was still metastasis free at 10 years.
"The EndoPredict score identifies early and late recurrences, and offers independent prognostic information beyond what can be achieved with all common clinical parameters," Dr. Dubsky maintained.
"Why would this data be important?" he asked. "We currently have around 20,000 women included in ongoing extended/late endocrine therapy clinical trials. Speaking from our trial, ABCSG-16, also known as SALSA [Secondary Adjuvant Long-Term Study With Arimidex], we see very low event rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple," he explained. "We believe that gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice."
Dr. Laura Esserman of the University of California, San Francisco, asked how EndoPredict might stack up against other similar tools, such as the sensitivity to endocrine therapy (SET) index.
"I’d love to run this side by side in the same biomarker sample. That would be great," Dr. Dubsky commented. "We have had a fantastic presentation on the BCI (Breast Cancer Index), but this is a score that runs only in node-negative. And I think what is similar between the EndoPredict score and the BCI is that the BCI also has the ER signaling incorporated in the algorithm of genes."
Another attendee likewise asked whether the investigators had compared EndoPredict with tools such as Adjuvant Online.
"I’d be very careful with prediction power and comparing, because this is always going to depend on the biomarkers that you are using," Dr. Dubsky replied. "We have a fantastic sensitivity with this test, but how would another test from another company perform in the same biomarker sample, I cannot say."
"Would you not enrich your gene signature for late recurrence by simply examining patients who recurred late, and compare them with those that did not?" a third attendee wondered.
"The women assigned to the low-risk group have a very, very low incidence of both early and late recurrence; the high-risk group has a high risk of both early and late recurrence. The signature does in no way select specifically for the late recurrence," Dr. Dubsky explained. "I think what is special about the signature is that it can predict the late recurrences better than others do because it is not relying solely on proliferation."
Giving some background to the study, he noted, "The first-generation multigene signatures have largely been trained to predict early recurrences and not late recurrences, and commonly fail to identify the late events."
EndoPredict may be the first multigene test for breast cancer that can be used in a decentralized setting. The test has recently received the European CE mark as an in vitro diagnostic test, and is being used in Germany, Austria, and Switzerland.
The 1,702 postmenopausal women studied were participants in a pair of randomized trials (ABCSG-6 and ABCSG-8). One-third had node-positive disease. None received adjuvant chemotherapy, but all received hormonal therapy (tamoxifen alone or some sequence of tamoxifen and an aromatase inhibitor) for 5 years. Their median age was 64 years.
"This is a very homogeneously treated cohort with low to intermediate risk," Dr. Dubsky summarized.
A total of 998 women were still at risk for distant metastases after 5 years, and their median duration of follow-up was 7.1 years.
Overall, 49% of all patients had a low-risk EndoPredict score. After multivariate adjustment, these patients were significantly more likely to be free of distant metastases in the first 5 years of follow-up (hazard ratio, 1.20; P less than .001) and thereafter (HR, 1.28; P = .001). Fully 96.3% of patients with a low-risk score were metastasis free between 5 and 10 years.
"The EndoPredict is clearly an independent prognostic parameter both in the years 0 to 5 and after 5 years," Dr. Dubsky maintained.
When the C-index for discrimination was calculated, EndoPredict significantly improved on prediction of distant metastases after 5 years of follow-up when combined with the Adjuvant Online score (P less than .001) and other factors.
However, the best prediction was achieved with the predefined EndoPredict clinical score, which combined the EndoPredict score, nodal status, and tumor size, and achieved a C-index of nearly 0.8.
Fully 64% of patients still at risk for distant metastases after 5 years of follow-up had a low EndoPredict clinical score. These patients were dramatically more likely to remain free of distant metastases thereafter (HR, 5.11; P less than .001). In absolute terms, 98.2% were free of distant metastasis at 10 years.
"Risks and side effects of extended therapy should be weighed against this outcome," Dr. Dubsky recommended.
In a final analysis teasing apart the role of various genes included in the EndoPredict score, the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent positive prognostic information for late recurrence.
Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.
AT THE SAN ANTONIO BREAST CANCER SYMPOSIUM
Major Finding: Patients with a low vs. high EndoPredict clinical score at 5 years of follow-up were five times as likely to be free of distant metastases thereafter. Fully 98.2% of this group remained free of distant metastasis at 10 years.
Data Source: A secondary analysis of data from 1,702 postmenopausal women with ER-positive, HER2-negative early breast cancer treated with hormonal therapy in a pair of randomized trials (ABCSG-6 and ABCSG-8 trials)
Disclosures: Dr. Dubsky disclosed that he is an adviser to Sividon, Agendia, Genomic Health, and AstraZeneca; receives grant support from Sividon and Agendia; and is on the speakers bureau for Sividon.
New geriatric assessments aid cancer treatment decisions
SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.
The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.
While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.
A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.
"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.
Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.
He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).
The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.
The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.
"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.
Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.
Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.
"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.
Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.
"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.
Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.
Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.
For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.
Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.
"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.
Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.
SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.
The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.
While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.
A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.
"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.
Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.
He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).
The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.
The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.
"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.
Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.
Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.
"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.
Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.
"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.
Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.
Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.
For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.
Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.
"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.
Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.
SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.
The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.
While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.
A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.
"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.
Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.
He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).
The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.
The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.
"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.
Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.
Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.
"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.
Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.
"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.
Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.
Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.
For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.
Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.
"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.
Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.
EXPERT ANALYSIS FROM THE ANNUAL SAN ANTONIO BREAST CANCER SYMPOSIUM
Primary care inaccurately estimates cancer risk
Primary care physicians’ assessments of the risks and benefits of cancer screening didn’t match with reality, based on the results of a survey of beliefs and behaviors around cancer risk.
"We were really surprised at the high percentage of physicians who were inaccurately estimating risk," said Dr. Laura-Mae Baldwin, professor of family medicine at the University of Washington, Seattle, who presented on behalf of her colleagues a slice of data from the survey of 3,200 physicians. "This has the potential for average-risk patients to receive unnecessary testing, and for high-risk patients to miss opportunities for prevention or early detection."
The cross-sectional national survey used the 2008 American Medical Association master file to randomly sample family physicians, general internists, and obstetrician-gynecologists. The physicians were all under age 65 and practiced in either a hospital or an office. They were contacted by mail, and given encouragement in the form of a $20 bill. In a second mailing, nonresponders received a written note from Dr. Baldwin. Overall, there was a 62% response rate: 591 family physicians, 414 general internists, and 569 ob.gyns. took part.
Survey participants were given a 12-page booklet with a particular patient vignette and a photo of the patient. The example included a medical and family history, along with age, race, sex, insurance status, and some other characteristics.
The researchers focused on ovarian cancer in particular because the Centers for Disease Control and Prevention, which funded the study, had a special interest in that cancer.
For instance, one vignette presented a 51-year-old white woman who came in because she wanted to be sure she was up to date on various tests. She had no medical problems, but had not seen a physician in 3 years. Her father had hypertension and her mother died of ovarian cancer at age 65. The other family history was negative, and there was an unremarkable physical exam.
The researchers had 258 variations for the different vignettes, varying age, race, insurance status, whether the patient asked for ovarian cancer screening, and family history. Physicians were asked to give their best estimate for this patient, and for other example patients, of risk for breast, ovarian, and colon cancer. They were asked to state whether the patient had a risk that was the same as that of the general population, somewhat higher, or much higher.
For a woman who was at the same risk as the general population for ovarian cancer, 72% of physicians were in agreement. However, 26% estimated the women were at somewhat higher risk and 1%, at much higher risk. For women at somewhat higher risk for ovarian cancer, however, 7% of physicians correctly assessed risk. Risk was assessed as somewhat higher or much higher by 90%, Dr. Baldwin reported at the annual meeting of the North American Primary Care Research Group.
For a woman at high risk for ovarian cancer, 35% of physicians correctly estimated that risk. Most physicians estimated risk as somewhat higher, but 11% thought her risk was the same as that for the general population.
The assessments of risk for colon cancer were similarly inaccurate. For the vignette of the woman at the same risk as the general population, 62% of physicians were on target, and 39% overestimated the risk.
There were no significant differences among the specialties, but ob.gyns. tended to be more accurate in their screening decisions, said Dr. Baldwin. An analysis showed that providers’ personal history with cancer influenced their recommended screening behaviors, said Dr. Baldwin. She did not present specific data on that issue.
The study did have some limitations in that physicians were given somewhat limited information about the patient’s risk. Dr. Baldwin said it’s important to study physician behaviors further, especially since so many in the survey underestimated risk in a woman who clearly was at high risk for ovarian cancer.
Primary care physicians’ assessments of the risks and benefits of cancer screening didn’t match with reality, based on the results of a survey of beliefs and behaviors around cancer risk.
"We were really surprised at the high percentage of physicians who were inaccurately estimating risk," said Dr. Laura-Mae Baldwin, professor of family medicine at the University of Washington, Seattle, who presented on behalf of her colleagues a slice of data from the survey of 3,200 physicians. "This has the potential for average-risk patients to receive unnecessary testing, and for high-risk patients to miss opportunities for prevention or early detection."
The cross-sectional national survey used the 2008 American Medical Association master file to randomly sample family physicians, general internists, and obstetrician-gynecologists. The physicians were all under age 65 and practiced in either a hospital or an office. They were contacted by mail, and given encouragement in the form of a $20 bill. In a second mailing, nonresponders received a written note from Dr. Baldwin. Overall, there was a 62% response rate: 591 family physicians, 414 general internists, and 569 ob.gyns. took part.
Survey participants were given a 12-page booklet with a particular patient vignette and a photo of the patient. The example included a medical and family history, along with age, race, sex, insurance status, and some other characteristics.
The researchers focused on ovarian cancer in particular because the Centers for Disease Control and Prevention, which funded the study, had a special interest in that cancer.
For instance, one vignette presented a 51-year-old white woman who came in because she wanted to be sure she was up to date on various tests. She had no medical problems, but had not seen a physician in 3 years. Her father had hypertension and her mother died of ovarian cancer at age 65. The other family history was negative, and there was an unremarkable physical exam.
The researchers had 258 variations for the different vignettes, varying age, race, insurance status, whether the patient asked for ovarian cancer screening, and family history. Physicians were asked to give their best estimate for this patient, and for other example patients, of risk for breast, ovarian, and colon cancer. They were asked to state whether the patient had a risk that was the same as that of the general population, somewhat higher, or much higher.
For a woman who was at the same risk as the general population for ovarian cancer, 72% of physicians were in agreement. However, 26% estimated the women were at somewhat higher risk and 1%, at much higher risk. For women at somewhat higher risk for ovarian cancer, however, 7% of physicians correctly assessed risk. Risk was assessed as somewhat higher or much higher by 90%, Dr. Baldwin reported at the annual meeting of the North American Primary Care Research Group.
For a woman at high risk for ovarian cancer, 35% of physicians correctly estimated that risk. Most physicians estimated risk as somewhat higher, but 11% thought her risk was the same as that for the general population.
The assessments of risk for colon cancer were similarly inaccurate. For the vignette of the woman at the same risk as the general population, 62% of physicians were on target, and 39% overestimated the risk.
There were no significant differences among the specialties, but ob.gyns. tended to be more accurate in their screening decisions, said Dr. Baldwin. An analysis showed that providers’ personal history with cancer influenced their recommended screening behaviors, said Dr. Baldwin. She did not present specific data on that issue.
The study did have some limitations in that physicians were given somewhat limited information about the patient’s risk. Dr. Baldwin said it’s important to study physician behaviors further, especially since so many in the survey underestimated risk in a woman who clearly was at high risk for ovarian cancer.
Primary care physicians’ assessments of the risks and benefits of cancer screening didn’t match with reality, based on the results of a survey of beliefs and behaviors around cancer risk.
"We were really surprised at the high percentage of physicians who were inaccurately estimating risk," said Dr. Laura-Mae Baldwin, professor of family medicine at the University of Washington, Seattle, who presented on behalf of her colleagues a slice of data from the survey of 3,200 physicians. "This has the potential for average-risk patients to receive unnecessary testing, and for high-risk patients to miss opportunities for prevention or early detection."
The cross-sectional national survey used the 2008 American Medical Association master file to randomly sample family physicians, general internists, and obstetrician-gynecologists. The physicians were all under age 65 and practiced in either a hospital or an office. They were contacted by mail, and given encouragement in the form of a $20 bill. In a second mailing, nonresponders received a written note from Dr. Baldwin. Overall, there was a 62% response rate: 591 family physicians, 414 general internists, and 569 ob.gyns. took part.
Survey participants were given a 12-page booklet with a particular patient vignette and a photo of the patient. The example included a medical and family history, along with age, race, sex, insurance status, and some other characteristics.
The researchers focused on ovarian cancer in particular because the Centers for Disease Control and Prevention, which funded the study, had a special interest in that cancer.
For instance, one vignette presented a 51-year-old white woman who came in because she wanted to be sure she was up to date on various tests. She had no medical problems, but had not seen a physician in 3 years. Her father had hypertension and her mother died of ovarian cancer at age 65. The other family history was negative, and there was an unremarkable physical exam.
The researchers had 258 variations for the different vignettes, varying age, race, insurance status, whether the patient asked for ovarian cancer screening, and family history. Physicians were asked to give their best estimate for this patient, and for other example patients, of risk for breast, ovarian, and colon cancer. They were asked to state whether the patient had a risk that was the same as that of the general population, somewhat higher, or much higher.
For a woman who was at the same risk as the general population for ovarian cancer, 72% of physicians were in agreement. However, 26% estimated the women were at somewhat higher risk and 1%, at much higher risk. For women at somewhat higher risk for ovarian cancer, however, 7% of physicians correctly assessed risk. Risk was assessed as somewhat higher or much higher by 90%, Dr. Baldwin reported at the annual meeting of the North American Primary Care Research Group.
For a woman at high risk for ovarian cancer, 35% of physicians correctly estimated that risk. Most physicians estimated risk as somewhat higher, but 11% thought her risk was the same as that for the general population.
The assessments of risk for colon cancer were similarly inaccurate. For the vignette of the woman at the same risk as the general population, 62% of physicians were on target, and 39% overestimated the risk.
There were no significant differences among the specialties, but ob.gyns. tended to be more accurate in their screening decisions, said Dr. Baldwin. An analysis showed that providers’ personal history with cancer influenced their recommended screening behaviors, said Dr. Baldwin. She did not present specific data on that issue.
The study did have some limitations in that physicians were given somewhat limited information about the patient’s risk. Dr. Baldwin said it’s important to study physician behaviors further, especially since so many in the survey underestimated risk in a woman who clearly was at high risk for ovarian cancer.
AT THE ANNUAL MEETING OF THE NORTH AMERICAN PRIMARY CARE RESEARCH GROUP
Major Finding: For a woman at high risk for ovarian cancer, 35% of surveyed physicians correctly estimated that risk, and 11% thought her risk was the same as that for the general population.
Data Source: Data from a national, cross-sectional survey of 3,200 physicians.
Disclosures: The study was funded by the Centers for Disease Control and Prevention.
Variation by age in neutropenic complications among patients with cancer receiving chemotherapy
Background Age is among the most important risk factors for neutropenia-related hospitalization, but evidence is limited regarding the relative contributions of age and other risk factors.
Objective To explore the associations among patient age, other risk factors, and neutropenic complications in patients with cancer receiving myelosuppressive chemotherapy.
Methods This retrospective cohort study, which used a US commercial insurance claims database, included patients aged 40 years or older with non-Hodgkin lymphoma (NHL), breast cancer, or lung cancer who initiated chemotherapy between January 1, 2006 and March 31, 2010. The primary endpoint was the risk of neutropenia-related hospitalization during the first chemotherapy course. We used cubic spline modeling to estimate the association between neutropenia-related hospitalization and age, adjusting for patient and treatment characteristics. Logistic regression analyses examined the effects of other risk factors.
Results A total of 15,638 patients were included (NHL, n = 2,506; breast cancer, n = 9,110; lung cancer, n = 4,022), mean age 56-66 years. Neutropenia-related hospitalization occurred in 8.7% of NHL patients, 4.2% of breast cancer patients, and 3.9% of lung cancer patients. The association between age and the risk of neutropenia-related hospitalization was stronger in NHL than in lung or breast cancer. Patient comorbidities and chemotherapy characteristics had considerable effects on risk of neutropenia-related hospitalization.
Limitations Disease stage and other clinical factors could not be identified from the claims data.
Conclusion In addition to age, oncologists should evaluate individual patient risk factors including patient comorbidities and type of chemotherapy regimen.
*To read the full article, click on the PDF icon at the top of this introduction.
Background Age is among the most important risk factors for neutropenia-related hospitalization, but evidence is limited regarding the relative contributions of age and other risk factors.
Objective To explore the associations among patient age, other risk factors, and neutropenic complications in patients with cancer receiving myelosuppressive chemotherapy.
Methods This retrospective cohort study, which used a US commercial insurance claims database, included patients aged 40 years or older with non-Hodgkin lymphoma (NHL), breast cancer, or lung cancer who initiated chemotherapy between January 1, 2006 and March 31, 2010. The primary endpoint was the risk of neutropenia-related hospitalization during the first chemotherapy course. We used cubic spline modeling to estimate the association between neutropenia-related hospitalization and age, adjusting for patient and treatment characteristics. Logistic regression analyses examined the effects of other risk factors.
Results A total of 15,638 patients were included (NHL, n = 2,506; breast cancer, n = 9,110; lung cancer, n = 4,022), mean age 56-66 years. Neutropenia-related hospitalization occurred in 8.7% of NHL patients, 4.2% of breast cancer patients, and 3.9% of lung cancer patients. The association between age and the risk of neutropenia-related hospitalization was stronger in NHL than in lung or breast cancer. Patient comorbidities and chemotherapy characteristics had considerable effects on risk of neutropenia-related hospitalization.
Limitations Disease stage and other clinical factors could not be identified from the claims data.
Conclusion In addition to age, oncologists should evaluate individual patient risk factors including patient comorbidities and type of chemotherapy regimen.
*To read the full article, click on the PDF icon at the top of this introduction.
Background Age is among the most important risk factors for neutropenia-related hospitalization, but evidence is limited regarding the relative contributions of age and other risk factors.
Objective To explore the associations among patient age, other risk factors, and neutropenic complications in patients with cancer receiving myelosuppressive chemotherapy.
Methods This retrospective cohort study, which used a US commercial insurance claims database, included patients aged 40 years or older with non-Hodgkin lymphoma (NHL), breast cancer, or lung cancer who initiated chemotherapy between January 1, 2006 and March 31, 2010. The primary endpoint was the risk of neutropenia-related hospitalization during the first chemotherapy course. We used cubic spline modeling to estimate the association between neutropenia-related hospitalization and age, adjusting for patient and treatment characteristics. Logistic regression analyses examined the effects of other risk factors.
Results A total of 15,638 patients were included (NHL, n = 2,506; breast cancer, n = 9,110; lung cancer, n = 4,022), mean age 56-66 years. Neutropenia-related hospitalization occurred in 8.7% of NHL patients, 4.2% of breast cancer patients, and 3.9% of lung cancer patients. The association between age and the risk of neutropenia-related hospitalization was stronger in NHL than in lung or breast cancer. Patient comorbidities and chemotherapy characteristics had considerable effects on risk of neutropenia-related hospitalization.
Limitations Disease stage and other clinical factors could not be identified from the claims data.
Conclusion In addition to age, oncologists should evaluate individual patient risk factors including patient comorbidities and type of chemotherapy regimen.
*To read the full article, click on the PDF icon at the top of this introduction.
Tips on counseling women about mammography screening
Read Examining the Evidence: Is “overdiagnosis” of breast cancer common among women screened by mammography? by Dr. Kaunitz (January 2013)
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Read Examining the Evidence: Is “overdiagnosis” of breast cancer common among women screened by mammography? by Dr. Kaunitz (January 2013)
Read Examining the Evidence: Is “overdiagnosis” of breast cancer common among women screened by mammography? by Dr. Kaunitz (January 2013)
Is “overdiagnosis” of breast cancer common among women screened by mammography?
Women with ER-positive breast Ca may soon extend tamoxifen therapy to 10 years
To reduce deaths from cancer, screening should achieve two goals:
- It should lead to earlier detection of tumors likely to be fatal
- It should lead to better outcomes after treatment of these tumors.
In other words, effective screening increases the incidence of cancers identified at an early stage (when they have a better prognosis) as it reduces the incidence of malignancies detected at a late stage.
This study found that although screening does indeed increase the rate of detection of early-stage cancers, it reduces the diagnosis of late-stage malignancies only marginally.
Details of the trial
Using SEER data from 1976 through 2008, Bleyer and Welch looked for trends in the incidence of breast cancer—both early-stage malignancies (ductal carcinoma in situ and localized disease) and late-stage disease (regional and distant cancers)—among women aged 40 years or older. They also calculated the baseline incidence of breast cancer before screening using data from 1973, the first year that the rate of breast cancer was recorded. Because the incidence of breast cancer that year was “almost certainly spuriously low,” they also incorporated data from 1974 and 1975, when the rate of breast cancer was higher than average following the diagnosis of breast cancer in First Lady Betty Ford.
Bleyer and Welch also took measures to adjust for the higher incidence of breast cancer associated with the use of menopausal hormone therapy. To do so, they estimated the current incidence of breast cancer using data from 2006 through 2008, and they adjusted data for each year that the rate of breast cancer exceeded that figure from 1990 through 2005.
From 1976 through 2008, the rate of detection of early-stage disease more than doubled, increasing from 112 to 234 cancers per 100,000 women, while the detection of late-stage disease incrementally decreased, from 102 to 94 cancers per 100,000 women. Assuming a “constant underlying disease burden,” Bleyer and Welch estimated that only eight of the 122 additional early-stage cancers identified through screening were destined to progress to advanced disease. That means that 114 excess cases of breast cancer were detected per 100,000 women.
The number of women affected by overdiagnosis: an estimated 1.3 million, including more than 70,000 women in 2008 alone.
During the 30 years covered by this study, breast cancer deaths declined 28% among women aged 40 years and older (a population in which screening mammography was prevalent); among women younger than age 40 (a population in which screening was not prevalent), breast cancer mortality declined 42%. These declines are thought to be the result, largely, of advances in treatment.
Harms versus benefits of early detection
There is no question that screening mammography saves lives by promoting early diagnosis of breast cancer. However, as I stated above, the decline in breast cancer deaths identified in this study may be attributable more to improvements in treatment than to early diagnosis of breast cancer. This study also suggests that the benefits of screening mammography are overshadowed by the harms (including unnecessary diagnostic imaging, biopsies, surgery, chemotherapy, and radiation therapy) associated with overdiagnosis. From this perspective, a screening strategy for average-risk women in which mammography is initiated later, and is performed less frequently, would appear prudent. Accordingly, rather than adhere to guidelines from ACOG and other groups that recommend that screening be initiated earlier and performed annually, it makes more sense in average-risk women to follow the 2009 guidelines from the US Preventive Services Task Force, which recommend:
- biennial screening mammography for women aged 50 to 74 years
- biennial screening mammography before the age of 50 years only if, after counseling about the potential benefits and risks, the patient chooses this option.1
How these findings compare with other data
Three studies shed light on the efficacy of screening mammography in other populations. In an investigation from Norway, Kalager and colleagues examined the breast cancer mortality rate in four groups of women:
- those who lived in counties where screening mammography was performed during the years 1996 through 2005
- those who lived in counties where screening mammography was not performed (1996–2005)
- two historical comparison groups (1986–1995) that mirrored the first two groups.2
Their analysis of 40,075 women with breast cancer suggested that one-third of the reduction in breast cancer deaths during the time periods studied was the direct result of screening, whereas the bulk of the observed reduction in breast cancer mortality was attributed to greater breast cancer awareness, improved diagnostic (as opposed to screening) techniques, and enhancements in treatment.
In a look at breast cancer mortality within three pairs of European countries, Autier and colleagues concluded that screening did not directly contribute to the observed reduction in mortality.3 The country pairs were:
- Northern Ireland and the Republic of Ireland
- the Netherlands and Belgium/Flanders
- Sweden and Norway.
Each pair of countries offered comparable health-care services, had a similar prevalence of risk factors for breast cancer mortality, and experienced a similar reduction in breast cancer mortality from 1989 to 2006. However, implementation of mammography screening in these paired countries differed by approximately 10 to 15 years.
Last, in a meta-analysis from the United Kingdom, where women 50 to 70 years old are invited to be screened every 3 years, an independent panel concluded that mammography reduced breast cancer deaths but also led to overdiagnosis.4 Although the analysis included studies “with many limitations,” its findings suggest that one breast cancer death would be prevented for every three cases of overdiagnosis.
Improvements are expected
Thanks to a recent analysis of the breast cancer genome, in the future it may become possible to identify which breast tumors are likely to progress. Such an advance would allow clinicians to recommend treatment strategies in a highly selective fashion.5
The findings from this recent study make me that much more comfortable following the USPSTF guidelines for screening mammography. For average-risk women in their 40s, I do not push screening but am happy to arrange it if my patient would feel more comfortable being screened. However, if a woman in her 40s is at increased risk (eg, first-degree relative with breast cancer), I encourage her to undergo annual screens.
As for average-risk women in their 50s and older, I find that most of my patients continue to prefer annual screening, but I am supportive of screening every 18 or 24 months in this population.
Some ObGyns may wonder if they could be exposed to medicolegal risk if they do not follow ACOG guidelines. For example, what would happen if a patient in her 40s who has not been screened were diagnosed with breast cancer? I am not an attorney, but I know that the USPSTF guidelines represent a credible (many would say authoritative) resource for guidance related to mammography screening. Speaking of the USPSTF, it is worth pointing out that this body is made up of 16 primary care and public health physicians (including one ObGyn) who have no stake in regard to breast imaging. (See http://www.uspreventiveservicestaskforce.org/members.htm.)
It’s my view that radiologists who provide screening breast imaging services can play an important role in educating women about the pros and cons of mammography. Looking to the future, perhaps women checking in for a screening mammogram will be asked to review and sign a document that clearly explains benefits (eg, reducing mortality through early diagnosis) as well as risks (eg, the occurrence and consequences of overdiagnosis: finding cancers that are destined not to not to cause advanced disease).
ANDREW M. KAUNITZ, MD
We want to hear from you! Tell us what you think.
1. US Preventive Services Task Force Screening for Breast Cancer. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm. Accessed December 18 2012.
2. Kalager M, Zelen M, Langmark F, Adami H-O. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363:1203-1210.
3. Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011;343:d4411.-
4. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855):1778-1786.
5. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
Yes. This analysis of Surveillance, Epidemiology, and End Results (SEER) data from a 30-year span indicates that nearly one-third of all breast malignancies identified during screening are overdiagnosed—that is, they are unlikely ever to lead to clinical symptoms.
| Dr. Kaunitz offers tips on counseling women about mammography screening |
Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367(21):1998–2005.
EXPERT COMMENTARY
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Yes. This analysis of Surveillance, Epidemiology, and End Results (SEER) data from a 30-year span indicates that nearly one-third of all breast malignancies identified during screening are overdiagnosed—that is, they are unlikely ever to lead to clinical symptoms.
|
| Dr. Kaunitz offers tips on counseling women about mammography screening |
Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367(21):1998–2005.
EXPERT COMMENTARY
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Yes. This analysis of Surveillance, Epidemiology, and End Results (SEER) data from a 30-year span indicates that nearly one-third of all breast malignancies identified during screening are overdiagnosed—that is, they are unlikely ever to lead to clinical symptoms.
|
| Dr. Kaunitz offers tips on counseling women about mammography screening |
Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367(21):1998–2005.
EXPERT COMMENTARY
Andrew M. Kaunitz, MD
Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz serves on the OBG Management Board of Editors.
Women with ER-positive breast Ca may soon extend tamoxifen therapy to 10 years
To reduce deaths from cancer, screening should achieve two goals:
- It should lead to earlier detection of tumors likely to be fatal
- It should lead to better outcomes after treatment of these tumors.
In other words, effective screening increases the incidence of cancers identified at an early stage (when they have a better prognosis) as it reduces the incidence of malignancies detected at a late stage.
This study found that although screening does indeed increase the rate of detection of early-stage cancers, it reduces the diagnosis of late-stage malignancies only marginally.
Details of the trial
Using SEER data from 1976 through 2008, Bleyer and Welch looked for trends in the incidence of breast cancer—both early-stage malignancies (ductal carcinoma in situ and localized disease) and late-stage disease (regional and distant cancers)—among women aged 40 years or older. They also calculated the baseline incidence of breast cancer before screening using data from 1973, the first year that the rate of breast cancer was recorded. Because the incidence of breast cancer that year was “almost certainly spuriously low,” they also incorporated data from 1974 and 1975, when the rate of breast cancer was higher than average following the diagnosis of breast cancer in First Lady Betty Ford.
Bleyer and Welch also took measures to adjust for the higher incidence of breast cancer associated with the use of menopausal hormone therapy. To do so, they estimated the current incidence of breast cancer using data from 2006 through 2008, and they adjusted data for each year that the rate of breast cancer exceeded that figure from 1990 through 2005.
From 1976 through 2008, the rate of detection of early-stage disease more than doubled, increasing from 112 to 234 cancers per 100,000 women, while the detection of late-stage disease incrementally decreased, from 102 to 94 cancers per 100,000 women. Assuming a “constant underlying disease burden,” Bleyer and Welch estimated that only eight of the 122 additional early-stage cancers identified through screening were destined to progress to advanced disease. That means that 114 excess cases of breast cancer were detected per 100,000 women.
The number of women affected by overdiagnosis: an estimated 1.3 million, including more than 70,000 women in 2008 alone.
During the 30 years covered by this study, breast cancer deaths declined 28% among women aged 40 years and older (a population in which screening mammography was prevalent); among women younger than age 40 (a population in which screening was not prevalent), breast cancer mortality declined 42%. These declines are thought to be the result, largely, of advances in treatment.
Harms versus benefits of early detection
There is no question that screening mammography saves lives by promoting early diagnosis of breast cancer. However, as I stated above, the decline in breast cancer deaths identified in this study may be attributable more to improvements in treatment than to early diagnosis of breast cancer. This study also suggests that the benefits of screening mammography are overshadowed by the harms (including unnecessary diagnostic imaging, biopsies, surgery, chemotherapy, and radiation therapy) associated with overdiagnosis. From this perspective, a screening strategy for average-risk women in which mammography is initiated later, and is performed less frequently, would appear prudent. Accordingly, rather than adhere to guidelines from ACOG and other groups that recommend that screening be initiated earlier and performed annually, it makes more sense in average-risk women to follow the 2009 guidelines from the US Preventive Services Task Force, which recommend:
- biennial screening mammography for women aged 50 to 74 years
- biennial screening mammography before the age of 50 years only if, after counseling about the potential benefits and risks, the patient chooses this option.1
How these findings compare with other data
Three studies shed light on the efficacy of screening mammography in other populations. In an investigation from Norway, Kalager and colleagues examined the breast cancer mortality rate in four groups of women:
- those who lived in counties where screening mammography was performed during the years 1996 through 2005
- those who lived in counties where screening mammography was not performed (1996–2005)
- two historical comparison groups (1986–1995) that mirrored the first two groups.2
Their analysis of 40,075 women with breast cancer suggested that one-third of the reduction in breast cancer deaths during the time periods studied was the direct result of screening, whereas the bulk of the observed reduction in breast cancer mortality was attributed to greater breast cancer awareness, improved diagnostic (as opposed to screening) techniques, and enhancements in treatment.
In a look at breast cancer mortality within three pairs of European countries, Autier and colleagues concluded that screening did not directly contribute to the observed reduction in mortality.3 The country pairs were:
- Northern Ireland and the Republic of Ireland
- the Netherlands and Belgium/Flanders
- Sweden and Norway.
Each pair of countries offered comparable health-care services, had a similar prevalence of risk factors for breast cancer mortality, and experienced a similar reduction in breast cancer mortality from 1989 to 2006. However, implementation of mammography screening in these paired countries differed by approximately 10 to 15 years.
Last, in a meta-analysis from the United Kingdom, where women 50 to 70 years old are invited to be screened every 3 years, an independent panel concluded that mammography reduced breast cancer deaths but also led to overdiagnosis.4 Although the analysis included studies “with many limitations,” its findings suggest that one breast cancer death would be prevented for every three cases of overdiagnosis.
Improvements are expected
Thanks to a recent analysis of the breast cancer genome, in the future it may become possible to identify which breast tumors are likely to progress. Such an advance would allow clinicians to recommend treatment strategies in a highly selective fashion.5
The findings from this recent study make me that much more comfortable following the USPSTF guidelines for screening mammography. For average-risk women in their 40s, I do not push screening but am happy to arrange it if my patient would feel more comfortable being screened. However, if a woman in her 40s is at increased risk (eg, first-degree relative with breast cancer), I encourage her to undergo annual screens.
As for average-risk women in their 50s and older, I find that most of my patients continue to prefer annual screening, but I am supportive of screening every 18 or 24 months in this population.
Some ObGyns may wonder if they could be exposed to medicolegal risk if they do not follow ACOG guidelines. For example, what would happen if a patient in her 40s who has not been screened were diagnosed with breast cancer? I am not an attorney, but I know that the USPSTF guidelines represent a credible (many would say authoritative) resource for guidance related to mammography screening. Speaking of the USPSTF, it is worth pointing out that this body is made up of 16 primary care and public health physicians (including one ObGyn) who have no stake in regard to breast imaging. (See http://www.uspreventiveservicestaskforce.org/members.htm.)
It’s my view that radiologists who provide screening breast imaging services can play an important role in educating women about the pros and cons of mammography. Looking to the future, perhaps women checking in for a screening mammogram will be asked to review and sign a document that clearly explains benefits (eg, reducing mortality through early diagnosis) as well as risks (eg, the occurrence and consequences of overdiagnosis: finding cancers that are destined not to not to cause advanced disease).
ANDREW M. KAUNITZ, MD
We want to hear from you! Tell us what you think.
Women with ER-positive breast Ca may soon extend tamoxifen therapy to 10 years
To reduce deaths from cancer, screening should achieve two goals:
- It should lead to earlier detection of tumors likely to be fatal
- It should lead to better outcomes after treatment of these tumors.
In other words, effective screening increases the incidence of cancers identified at an early stage (when they have a better prognosis) as it reduces the incidence of malignancies detected at a late stage.
This study found that although screening does indeed increase the rate of detection of early-stage cancers, it reduces the diagnosis of late-stage malignancies only marginally.
Details of the trial
Using SEER data from 1976 through 2008, Bleyer and Welch looked for trends in the incidence of breast cancer—both early-stage malignancies (ductal carcinoma in situ and localized disease) and late-stage disease (regional and distant cancers)—among women aged 40 years or older. They also calculated the baseline incidence of breast cancer before screening using data from 1973, the first year that the rate of breast cancer was recorded. Because the incidence of breast cancer that year was “almost certainly spuriously low,” they also incorporated data from 1974 and 1975, when the rate of breast cancer was higher than average following the diagnosis of breast cancer in First Lady Betty Ford.
Bleyer and Welch also took measures to adjust for the higher incidence of breast cancer associated with the use of menopausal hormone therapy. To do so, they estimated the current incidence of breast cancer using data from 2006 through 2008, and they adjusted data for each year that the rate of breast cancer exceeded that figure from 1990 through 2005.
From 1976 through 2008, the rate of detection of early-stage disease more than doubled, increasing from 112 to 234 cancers per 100,000 women, while the detection of late-stage disease incrementally decreased, from 102 to 94 cancers per 100,000 women. Assuming a “constant underlying disease burden,” Bleyer and Welch estimated that only eight of the 122 additional early-stage cancers identified through screening were destined to progress to advanced disease. That means that 114 excess cases of breast cancer were detected per 100,000 women.
The number of women affected by overdiagnosis: an estimated 1.3 million, including more than 70,000 women in 2008 alone.
During the 30 years covered by this study, breast cancer deaths declined 28% among women aged 40 years and older (a population in which screening mammography was prevalent); among women younger than age 40 (a population in which screening was not prevalent), breast cancer mortality declined 42%. These declines are thought to be the result, largely, of advances in treatment.
Harms versus benefits of early detection
There is no question that screening mammography saves lives by promoting early diagnosis of breast cancer. However, as I stated above, the decline in breast cancer deaths identified in this study may be attributable more to improvements in treatment than to early diagnosis of breast cancer. This study also suggests that the benefits of screening mammography are overshadowed by the harms (including unnecessary diagnostic imaging, biopsies, surgery, chemotherapy, and radiation therapy) associated with overdiagnosis. From this perspective, a screening strategy for average-risk women in which mammography is initiated later, and is performed less frequently, would appear prudent. Accordingly, rather than adhere to guidelines from ACOG and other groups that recommend that screening be initiated earlier and performed annually, it makes more sense in average-risk women to follow the 2009 guidelines from the US Preventive Services Task Force, which recommend:
- biennial screening mammography for women aged 50 to 74 years
- biennial screening mammography before the age of 50 years only if, after counseling about the potential benefits and risks, the patient chooses this option.1
How these findings compare with other data
Three studies shed light on the efficacy of screening mammography in other populations. In an investigation from Norway, Kalager and colleagues examined the breast cancer mortality rate in four groups of women:
- those who lived in counties where screening mammography was performed during the years 1996 through 2005
- those who lived in counties where screening mammography was not performed (1996–2005)
- two historical comparison groups (1986–1995) that mirrored the first two groups.2
Their analysis of 40,075 women with breast cancer suggested that one-third of the reduction in breast cancer deaths during the time periods studied was the direct result of screening, whereas the bulk of the observed reduction in breast cancer mortality was attributed to greater breast cancer awareness, improved diagnostic (as opposed to screening) techniques, and enhancements in treatment.
In a look at breast cancer mortality within three pairs of European countries, Autier and colleagues concluded that screening did not directly contribute to the observed reduction in mortality.3 The country pairs were:
- Northern Ireland and the Republic of Ireland
- the Netherlands and Belgium/Flanders
- Sweden and Norway.
Each pair of countries offered comparable health-care services, had a similar prevalence of risk factors for breast cancer mortality, and experienced a similar reduction in breast cancer mortality from 1989 to 2006. However, implementation of mammography screening in these paired countries differed by approximately 10 to 15 years.
Last, in a meta-analysis from the United Kingdom, where women 50 to 70 years old are invited to be screened every 3 years, an independent panel concluded that mammography reduced breast cancer deaths but also led to overdiagnosis.4 Although the analysis included studies “with many limitations,” its findings suggest that one breast cancer death would be prevented for every three cases of overdiagnosis.
Improvements are expected
Thanks to a recent analysis of the breast cancer genome, in the future it may become possible to identify which breast tumors are likely to progress. Such an advance would allow clinicians to recommend treatment strategies in a highly selective fashion.5
The findings from this recent study make me that much more comfortable following the USPSTF guidelines for screening mammography. For average-risk women in their 40s, I do not push screening but am happy to arrange it if my patient would feel more comfortable being screened. However, if a woman in her 40s is at increased risk (eg, first-degree relative with breast cancer), I encourage her to undergo annual screens.
As for average-risk women in their 50s and older, I find that most of my patients continue to prefer annual screening, but I am supportive of screening every 18 or 24 months in this population.
Some ObGyns may wonder if they could be exposed to medicolegal risk if they do not follow ACOG guidelines. For example, what would happen if a patient in her 40s who has not been screened were diagnosed with breast cancer? I am not an attorney, but I know that the USPSTF guidelines represent a credible (many would say authoritative) resource for guidance related to mammography screening. Speaking of the USPSTF, it is worth pointing out that this body is made up of 16 primary care and public health physicians (including one ObGyn) who have no stake in regard to breast imaging. (See http://www.uspreventiveservicestaskforce.org/members.htm.)
It’s my view that radiologists who provide screening breast imaging services can play an important role in educating women about the pros and cons of mammography. Looking to the future, perhaps women checking in for a screening mammogram will be asked to review and sign a document that clearly explains benefits (eg, reducing mortality through early diagnosis) as well as risks (eg, the occurrence and consequences of overdiagnosis: finding cancers that are destined not to not to cause advanced disease).
ANDREW M. KAUNITZ, MD
We want to hear from you! Tell us what you think.
1. US Preventive Services Task Force Screening for Breast Cancer. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm. Accessed December 18 2012.
2. Kalager M, Zelen M, Langmark F, Adami H-O. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363:1203-1210.
3. Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011;343:d4411.-
4. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855):1778-1786.
5. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
1. US Preventive Services Task Force Screening for Breast Cancer. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm. Accessed December 18 2012.
2. Kalager M, Zelen M, Langmark F, Adami H-O. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363:1203-1210.
3. Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011;343:d4411.-
4. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855):1778-1786.
5. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
Genes predict adjuvant trastuzumab outcomes in HER2-positive breast cancer
SAN ANTONIO – Researchers have taken a first stride toward the goal of developing a gene test that predicts a breast cancer patient’s likelihood of a favorable clinical outcome in response to adjuvant trastuzumab.
A massive gene expression profiling analysis of baseline pretreatment tumor specimens obtained from 372 breast cancer patients identified 32 genes that correlated strongly with 5-year relapse-free survival, each with a P value less than .001, Dr. Edith A. Perez reported at the San Antonio Breast Cancer Symposium.
The ideal thing would be to find a gene that, if highly expressed, predicts for benefit or not of Herceptin [trastuzumab]. We are on our way to developing a predictive test that can define the right treatment for individual patients, and that is very exciting," declared Dr. Perez, deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the breast cancer translational genomics program at the Mayo Clinic in Jacksonville, Fla.
In all, 27 of the genes were associated with good outcome, while the other 5 correlated with poor outcome. The major functional categories these genes are involved in have been identified: cell receptor signaling, chromatin structure and transcription, control of cell death, cell cycle, Wnt/beta-catenin signaling, and lipid signaling. It’s not yet known whether these 32 genes are expressed in the epithelial or the stromal component of the tumors, and it will be challenging to figure that out, she said.
All 372 specimens in this analysis came from women randomized to adjuvant chemotherapy plus concurrent trastuzumab in the previously reported North Central Cancer Treatment Group N9831 trial. The N9831 trial was one of the pivotal studies that led to adjuvant trastuzumab plus chemotherapy becoming established as the standard of care in treating HER2-positive breast cancer
Dr. Perez and her coinvestigators have also just completed a gene expression profiling analysis of baseline tumor samples from an additional 910 women in the N9831 trial who were randomized to either chemotherapy alone or chemotherapy followed sequentially by trastuzumab. The plan is to identify similarities and differences in the patterns of gene expression in the chemotherapy-only and the two chemotherapy-plus-trastuzumab groups in order to home in more specifically on genes associated with the outcome of trastuzumab therapy. Those data weren’t ready for presentation at the symposium.
The study used the DNA-mediated DASL (annealing, extension, selection, and ligation) assay marketed by Illumina to scrutinize the activity of more than 29,000 genes in tumor specimens from 1,262 N9831 trial participants.
In addition, Dr. Perez and her coworkers are collaborating with other investigators around the world who also conducted adjuvant trastuzumab trials with collections of tumor samples, including the HERA (Herceptin Adjuvant) and FinHer studies, in order to carry out a validation study.
Discussant Dr. Dennis C. Sgroi called this work tremendously exciting. He noted that trastuzumab is a very expensive drug, and roughly 25% of treated patients relapse within 5 years. Trastuzumab also carries a risk of cardiotoxicity, and he was intrigued by Dr. Perez’ suggestion that the investigators believe they may have identified baseline tumor gene activity signatures predisposing to symptomatic cardiomyopathy and transient asymptomatic drops in left ventricular ejection fraction.
A noteworthy aspect of this study is that many of the 32 predictive genomic markers that were identified function in domains other than proliferation. Genes that figure in proliferation are the predominant drivers of the prognostic performance of Genomic Health’s Oncotype DX and all the other molecular biomarker assays developed to date. So the work of Dr. Perez and her coinvestigators is definitely next-generation in the molecular profiling arena, said Dr. Sgroi of Massachusetts General Hospital, Boston.
This study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, and the 26.2 with Donna Foundation. Dr. Perez reported no financial conflicts.
SAN ANTONIO – Researchers have taken a first stride toward the goal of developing a gene test that predicts a breast cancer patient’s likelihood of a favorable clinical outcome in response to adjuvant trastuzumab.
A massive gene expression profiling analysis of baseline pretreatment tumor specimens obtained from 372 breast cancer patients identified 32 genes that correlated strongly with 5-year relapse-free survival, each with a P value less than .001, Dr. Edith A. Perez reported at the San Antonio Breast Cancer Symposium.
The ideal thing would be to find a gene that, if highly expressed, predicts for benefit or not of Herceptin [trastuzumab]. We are on our way to developing a predictive test that can define the right treatment for individual patients, and that is very exciting," declared Dr. Perez, deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the breast cancer translational genomics program at the Mayo Clinic in Jacksonville, Fla.
In all, 27 of the genes were associated with good outcome, while the other 5 correlated with poor outcome. The major functional categories these genes are involved in have been identified: cell receptor signaling, chromatin structure and transcription, control of cell death, cell cycle, Wnt/beta-catenin signaling, and lipid signaling. It’s not yet known whether these 32 genes are expressed in the epithelial or the stromal component of the tumors, and it will be challenging to figure that out, she said.
All 372 specimens in this analysis came from women randomized to adjuvant chemotherapy plus concurrent trastuzumab in the previously reported North Central Cancer Treatment Group N9831 trial. The N9831 trial was one of the pivotal studies that led to adjuvant trastuzumab plus chemotherapy becoming established as the standard of care in treating HER2-positive breast cancer
Dr. Perez and her coinvestigators have also just completed a gene expression profiling analysis of baseline tumor samples from an additional 910 women in the N9831 trial who were randomized to either chemotherapy alone or chemotherapy followed sequentially by trastuzumab. The plan is to identify similarities and differences in the patterns of gene expression in the chemotherapy-only and the two chemotherapy-plus-trastuzumab groups in order to home in more specifically on genes associated with the outcome of trastuzumab therapy. Those data weren’t ready for presentation at the symposium.
The study used the DNA-mediated DASL (annealing, extension, selection, and ligation) assay marketed by Illumina to scrutinize the activity of more than 29,000 genes in tumor specimens from 1,262 N9831 trial participants.
In addition, Dr. Perez and her coworkers are collaborating with other investigators around the world who also conducted adjuvant trastuzumab trials with collections of tumor samples, including the HERA (Herceptin Adjuvant) and FinHer studies, in order to carry out a validation study.
Discussant Dr. Dennis C. Sgroi called this work tremendously exciting. He noted that trastuzumab is a very expensive drug, and roughly 25% of treated patients relapse within 5 years. Trastuzumab also carries a risk of cardiotoxicity, and he was intrigued by Dr. Perez’ suggestion that the investigators believe they may have identified baseline tumor gene activity signatures predisposing to symptomatic cardiomyopathy and transient asymptomatic drops in left ventricular ejection fraction.
A noteworthy aspect of this study is that many of the 32 predictive genomic markers that were identified function in domains other than proliferation. Genes that figure in proliferation are the predominant drivers of the prognostic performance of Genomic Health’s Oncotype DX and all the other molecular biomarker assays developed to date. So the work of Dr. Perez and her coinvestigators is definitely next-generation in the molecular profiling arena, said Dr. Sgroi of Massachusetts General Hospital, Boston.
This study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, and the 26.2 with Donna Foundation. Dr. Perez reported no financial conflicts.
SAN ANTONIO – Researchers have taken a first stride toward the goal of developing a gene test that predicts a breast cancer patient’s likelihood of a favorable clinical outcome in response to adjuvant trastuzumab.
A massive gene expression profiling analysis of baseline pretreatment tumor specimens obtained from 372 breast cancer patients identified 32 genes that correlated strongly with 5-year relapse-free survival, each with a P value less than .001, Dr. Edith A. Perez reported at the San Antonio Breast Cancer Symposium.
The ideal thing would be to find a gene that, if highly expressed, predicts for benefit or not of Herceptin [trastuzumab]. We are on our way to developing a predictive test that can define the right treatment for individual patients, and that is very exciting," declared Dr. Perez, deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the breast cancer translational genomics program at the Mayo Clinic in Jacksonville, Fla.
In all, 27 of the genes were associated with good outcome, while the other 5 correlated with poor outcome. The major functional categories these genes are involved in have been identified: cell receptor signaling, chromatin structure and transcription, control of cell death, cell cycle, Wnt/beta-catenin signaling, and lipid signaling. It’s not yet known whether these 32 genes are expressed in the epithelial or the stromal component of the tumors, and it will be challenging to figure that out, she said.
All 372 specimens in this analysis came from women randomized to adjuvant chemotherapy plus concurrent trastuzumab in the previously reported North Central Cancer Treatment Group N9831 trial. The N9831 trial was one of the pivotal studies that led to adjuvant trastuzumab plus chemotherapy becoming established as the standard of care in treating HER2-positive breast cancer
Dr. Perez and her coinvestigators have also just completed a gene expression profiling analysis of baseline tumor samples from an additional 910 women in the N9831 trial who were randomized to either chemotherapy alone or chemotherapy followed sequentially by trastuzumab. The plan is to identify similarities and differences in the patterns of gene expression in the chemotherapy-only and the two chemotherapy-plus-trastuzumab groups in order to home in more specifically on genes associated with the outcome of trastuzumab therapy. Those data weren’t ready for presentation at the symposium.
The study used the DNA-mediated DASL (annealing, extension, selection, and ligation) assay marketed by Illumina to scrutinize the activity of more than 29,000 genes in tumor specimens from 1,262 N9831 trial participants.
In addition, Dr. Perez and her coworkers are collaborating with other investigators around the world who also conducted adjuvant trastuzumab trials with collections of tumor samples, including the HERA (Herceptin Adjuvant) and FinHer studies, in order to carry out a validation study.
Discussant Dr. Dennis C. Sgroi called this work tremendously exciting. He noted that trastuzumab is a very expensive drug, and roughly 25% of treated patients relapse within 5 years. Trastuzumab also carries a risk of cardiotoxicity, and he was intrigued by Dr. Perez’ suggestion that the investigators believe they may have identified baseline tumor gene activity signatures predisposing to symptomatic cardiomyopathy and transient asymptomatic drops in left ventricular ejection fraction.
A noteworthy aspect of this study is that many of the 32 predictive genomic markers that were identified function in domains other than proliferation. Genes that figure in proliferation are the predominant drivers of the prognostic performance of Genomic Health’s Oncotype DX and all the other molecular biomarker assays developed to date. So the work of Dr. Perez and her coinvestigators is definitely next-generation in the molecular profiling arena, said Dr. Sgroi of Massachusetts General Hospital, Boston.
This study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, and the 26.2 with Donna Foundation. Dr. Perez reported no financial conflicts.
AT THE SAN ANTONIO BREAST CANCER SYMPOSIUM
Major Finding: Thirty-two genes strongly correlated with 5-year outcomes of adjuvant chemotherapy and trastuzumab therapy.
Data Source: A gene expression profiling study scrutinized more than 29,000 genes in baseline tumor samples from 372 breast cancer patients in the randomized N9831 trial.
Disclosures: This study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, and the 26.2 with Donna Foundation. Dr. Perez reported no financial conflicts.
SLN surgery may suffice for node-positive breast cancer
SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.
Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.
The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).
"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."
Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.
Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.
Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.
Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.
When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.
The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).
"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.
In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."
"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.
Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).
"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."
Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.
"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.
Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.
"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.
In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.
"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."
Dr. Boughey disclosed no relevant conflicts of interest.
SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.
Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.
The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).
"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."
Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.
Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.
Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.
Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.
When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.
The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).
"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.
In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."
"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.
Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).
"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."
Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.
"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.
Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.
"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.
In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.
"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."
Dr. Boughey disclosed no relevant conflicts of interest.
SAN ANTONIO – Women undergoing neoadjuvant chemotherapy for node-positive breast cancer may be able to have sentinel lymph node surgery instead of an axillary lymph node dissection, but proper surgical technique is critical for staging accuracy, a phase II trial from the American College of Surgeons Oncology Group suggests.
Among the 637 women studied in ACOSOG Z1071, all received chemotherapy and then underwent both sentinel lymph node (SLN) surgery and axillary lymph node dissection (ALND). SLN surgery correctly identified nodal status in 91.2% of cases, lead investigator Dr. Judy C. Boughey reported at the San Antonio Breast Cancer Symposium.
The false-negative rate of SLN averaged 12.6% in women with clinical N1 disease who had at least two sentinel nodes examined – slightly higher than the 10% set as a predefined endpoint. But it was lower when both blue dye and radiolabeled colloid were used to identify sentinel nodes (10.8%) and when three or more sentinel nodes were examined (9.1%).
"SLN surgery is a useful tool for detecting residual nodal disease in those women who present with node-positive breast cancer receiving neoadjuvant chemotherapy," Dr. Boughey commented in a press briefing. "Using SLN surgery in this patient population will enable us to reduce the extent of axillary surgery and therefore decrease morbidities for women treated for breast cancer."
Women were eligible for the trial if they had node-positive (T0-4, N1-2) breast cancer. After neoadjuvant chemotherapy, they underwent definitive breast surgery (lumpectomy or mastectomy), along with SLN surgery followed by a completion ALND. Patients who had N3 disease, inflammatory breast cancer, or prior ipsilateral axillary surgery were excluded.
Nodes were defined as being positive if they contained a tumor deposit measuring greater than 0.2 mm on sections stained with hematoxylin and eosin.
Sentinel nodes were identified in 92.7% of patients overall. A total of 40% of patients had no detectable nodal disease after neoadjuvant chemotherapy and thus would be unlikely to benefit from undergoing ALND, according to Dr. Boughey, a surgeon at the Mayo Clinic in Rochester, Minn.
Among the 60% of patients with detectable nodal disease (subsequently used to assess the false-negative rate of SLN), 85% had only positive sentinel nodes.
When only a single SLN was examined, the false-negative rate of SLN surgery was 31.5%, so Dr. Boughey recommends resecting a minimum of two nodes.
The false-negative rate was also lower when sentinel nodes were pathologically examined and determined to contain histologic changes (10.8%) and when a clip placed in the node at initial diagnosis was subsequently found at definitive surgery (7.4%).
"It’s important to collaborate with our radiology colleagues regarding potential for clip placement in lymph nodes, as well as our pathologists for review of sentinel lymph nodes for the presence of treatment effect," she said.
In the session where the results were presented, Dr. J. Michael Dixon of the Western General Hospital in Edinburgh asked whether a minimum of three nodes should be taken, because "if you take three or more nodes, your false-negative rate is within the range that is acceptable. Yet your conclusions said two. So I wonder if you get a second chance, you can tell us that we can do this technique if we use dual isotope and if we take three or more sentinel nodes and follow your other rules."
"We framed the conclusion based on the way the protocol had been written up front with two or more, but I think your comments are spot on," replied Dr. Boughey.
Dr. Steven Vogl of the Montefiore Medical Center in the Bronx, New York, asked about pathologic complete response (pCR).
"We did not require any specific degree of response for the patients to be in the study, since all of the patients were getting a completion ALND," Dr. Boughey replied. "We are currently evaluating specifically that question about whether the breast response and/or the nodal response on ultrasound can help define the appropriate patient population for us to tailor this therapy to."
Dr. Vogl noted that for patients who are HER2-positive, ER-negative, and triple-negative, pCR is very important. "So if we can figure out very carefully who didn’t achieve a pCR, especially in the node, we can probably do something for those patients some day with the right agents," he said.
"Do you use clips in all patients? Do you use dual agents always? And do you always remove two sentinel nodes? What is the impact of this on what we should do next?" asked session moderator Dr. Anthony Lucci Jr., of the University of Texas M.D. Anderson Cancer Center in Houston.
Dr. Boughey replied, "The take-home message is ... I’ll be looking at clip placement, making sure that we use dual-agent tracer for these cases, and ensuring that we do a thorough evaluation of the axilla and resecting any node that is radioactive, blue, or palpable.
"One of the concerns always when you are doing the sentinel node and you know you are doing a planned dissection [thereafter] is that the completeness of the evaluation of the axilla may not be quite as thorough as if you are closing as soon as you finish that sentinel node biopsy. So I think that is where the onus rests on the surgeon, so that we thoroughly evaluate the axilla and ensure this technique is as thorough as possible," she added.
In an additional analysis of patients with clinical N2 disease, the false-negative rate of SLN was 0%.
"Further work is under way regarding the secondary endpoint of this study, which will look at correlating the axillary ultrasound after chemotherapy with the false-negative rate. ... Maybe this can help improve patient selection for the procedure and further lower the false-negative rate," Dr. Boughey said. "We are also continuing to work to evaluate lymphedema rates and quality of life in these patients."
Dr. Boughey disclosed no relevant conflicts of interest.
AT THE SAN ANTONIO BREAST CANCER SYMPOSIUM
Major Finding: SLN surgery correctly identified axillary nodal status in 91.2% of patients. The false-negative rate was 12.6% among women with clinical N1 disease who had at least two sentinel nodes examined.
Data Source: A multicenter phase II trial involving 637 patients with node-positive breast cancer who received neoadjuvant chemotherapy (the ACOSOG Z1071 trial).
Disclosures: Dr. Boughey disclosed no relevant conflicts of interest.
