Breast Cancer ICYMI

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1

Key clinical point: Patients with obesity and stages I-III breast cancer (BC) who undergo mastectomy with immediate reconstruction have a higher likelihood of experiencing surgical complications than patients without obesity.

Major finding: Compared with patients who underwent lumpectomy, the risk for surgical complications was significantly higher in those who underwent mastectomy with (odds ratio [OR] 7.45; P < .0001) or without (OR 3.15; P  =  .002) immediate reconstruction. Moreover, obesity vs non-obesity was associated with worse surgical complications among patients undergoing mastectomy with reconstruction (OR 2.25; P  =  .02).

Study details: Findings are from a retrospective study including 692 patients with stages I-III BC who underwent surgery and received body composition measurements using bioelectrical impedance spectrometry.

Disclosures: This study did not disclose the funding source. SA Valente and HCF Moore declared serving as consultants for, receiving fees or grants from, or having contracts with various sources.

Source: Aleixo GFP et al. Association of body composition and surgical outcomes in patients with early-stage breast cancer. Breast Cancer Res Treat. 2023 (Aug 28). doi: 10.1007/s10549-023-07060-5

Key clinical point: Patients with obesity and stages I-III breast cancer (BC) who undergo mastectomy with immediate reconstruction have a higher likelihood of experiencing surgical complications than patients without obesity.

Major finding: Compared with patients who underwent lumpectomy, the risk for surgical complications was significantly higher in those who underwent mastectomy with (odds ratio [OR] 7.45; P < .0001) or without (OR 3.15; P  =  .002) immediate reconstruction. Moreover, obesity vs non-obesity was associated with worse surgical complications among patients undergoing mastectomy with reconstruction (OR 2.25; P  =  .02).

Study details: Findings are from a retrospective study including 692 patients with stages I-III BC who underwent surgery and received body composition measurements using bioelectrical impedance spectrometry.

Disclosures: This study did not disclose the funding source. SA Valente and HCF Moore declared serving as consultants for, receiving fees or grants from, or having contracts with various sources.

Source: Aleixo GFP et al. Association of body composition and surgical outcomes in patients with early-stage breast cancer. Breast Cancer Res Treat. 2023 (Aug 28). doi: 10.1007/s10549-023-07060-5

Key clinical point: Patients with obesity and stages I-III breast cancer (BC) who undergo mastectomy with immediate reconstruction have a higher likelihood of experiencing surgical complications than patients without obesity.

Major finding: Compared with patients who underwent lumpectomy, the risk for surgical complications was significantly higher in those who underwent mastectomy with (odds ratio [OR] 7.45; P < .0001) or without (OR 3.15; P  =  .002) immediate reconstruction. Moreover, obesity vs non-obesity was associated with worse surgical complications among patients undergoing mastectomy with reconstruction (OR 2.25; P  =  .02).

Study details: Findings are from a retrospective study including 692 patients with stages I-III BC who underwent surgery and received body composition measurements using bioelectrical impedance spectrometry.

Disclosures: This study did not disclose the funding source. SA Valente and HCF Moore declared serving as consultants for, receiving fees or grants from, or having contracts with various sources.

Source: Aleixo GFP et al. Association of body composition and surgical outcomes in patients with early-stage breast cancer. Breast Cancer Res Treat. 2023 (Aug 28). doi: 10.1007/s10549-023-07060-5