Clinical Edge Journal Scan

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.

Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.

Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.

Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively.  Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.

Erin Roesch, MD
The Cleveland Clinic

References:

Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.

Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.

Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.

Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.

Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.

Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.

Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively.  Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.

Erin Roesch, MD
The Cleveland Clinic

References:

Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.

Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.

Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.

Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.

Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.

Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.

Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively.  Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.

Erin Roesch, MD
The Cleveland Clinic

References:

Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.

Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.

Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.

Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).

Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).

Study details: A cohort study of 69,000 women aged 50-64 years

Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.

Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179

Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).

Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).

Study details: A cohort study of 69,000 women aged 50-64 years

Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.

Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179

Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).

Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).

Study details: A cohort study of 69,000 women aged 50-64 years

Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.

Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179

Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.

Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.

Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014. 

Disclosures: The authors report no conflicts of interest.

Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124

Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.

Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.

Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014. 

Disclosures: The authors report no conflicts of interest.

Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124

Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.

Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.

Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014. 

Disclosures: The authors report no conflicts of interest.

Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124

Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.

Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.

Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer. 

Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.

Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129

Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.

Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.

Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer. 

Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.

Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129

Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.

Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.

Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer. 

Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.

Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129

Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.

Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.

Study details: Review of 1,584,079 screenings in women aged 40-79 years.

Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.

Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.

Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.

Study details: Review of 1,584,079 screenings in women aged 40-79 years.

Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.

Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.

Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.

Study details: Review of 1,584,079 screenings in women aged 40-79 years.

Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.

Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.

Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.

Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).

Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.

Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.

Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.

Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).

Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.

Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.

Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.

Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).

Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.

Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.

Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.

Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.

Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.

Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.

Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.

Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.

Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.

Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.

Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.

Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.

Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.

Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.

Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.

Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School