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Dr. Abdou scans the journals so you don't have to!
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Yara Abdou, MD

Yara Abdou, MD
Vaginal estrogen therapy can be an effective treatment for menopausal genitourinary symptoms; however, there are concerns regarding the use of these agents in patients with breast cancer. A recent Danish observational cohort study1 showed no increased risk for recurrence or mortality with vaginal estrogen therapy overall, although a subgroup analysis showed an increased recurrence risk but not mortality in patients receiving an aromatase inhibitor. McVicker and colleagues evaluated the risk for breast cancer–specific mortality in two large female cohorts to determine whether the risk for mortality was higher in women using vaginal estrogen therapy. The analysis included 49,237 women with breast cancer, of which, 5% used vaginal estrogen therapy after a breast cancer diagnosis. Breast cancer–specific mortality was not worsened in patients who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio [HR] 0.77; 95% CI 0.63-0.94). This was also observed when the analysis was restricted to women with hormone-positive breast cancer (HR 0.88; 95% CI 0.62-1.25) or women using aromatase inhibitors (HR 0.72; 95% CI 0.58-0.91). Although, unlike the Danish study, this study did not look at breast cancer recurrence, these findings provide some reassurance that vaginal estrogen therapy can be considered if all other nonhormonal therapies fail to improve genitourinary symptoms. More studies are needed to validate these findings.

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

  1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112
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Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

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Author(s)
Yara Abdou, MD
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Yara Abdou, MD
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Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

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Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

Dr. Abdou scans the journals so you don't have to!
Dr. Abdou scans the journals so you don't have to!

Yara Abdou, MD
Vaginal estrogen therapy can be an effective treatment for menopausal genitourinary symptoms; however, there are concerns regarding the use of these agents in patients with breast cancer. A recent Danish observational cohort study1 showed no increased risk for recurrence or mortality with vaginal estrogen therapy overall, although a subgroup analysis showed an increased recurrence risk but not mortality in patients receiving an aromatase inhibitor. McVicker and colleagues evaluated the risk for breast cancer–specific mortality in two large female cohorts to determine whether the risk for mortality was higher in women using vaginal estrogen therapy. The analysis included 49,237 women with breast cancer, of which, 5% used vaginal estrogen therapy after a breast cancer diagnosis. Breast cancer–specific mortality was not worsened in patients who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio [HR] 0.77; 95% CI 0.63-0.94). This was also observed when the analysis was restricted to women with hormone-positive breast cancer (HR 0.88; 95% CI 0.62-1.25) or women using aromatase inhibitors (HR 0.72; 95% CI 0.58-0.91). Although, unlike the Danish study, this study did not look at breast cancer recurrence, these findings provide some reassurance that vaginal estrogen therapy can be considered if all other nonhormonal therapies fail to improve genitourinary symptoms. More studies are needed to validate these findings.

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

  1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112

Yara Abdou, MD
Vaginal estrogen therapy can be an effective treatment for menopausal genitourinary symptoms; however, there are concerns regarding the use of these agents in patients with breast cancer. A recent Danish observational cohort study1 showed no increased risk for recurrence or mortality with vaginal estrogen therapy overall, although a subgroup analysis showed an increased recurrence risk but not mortality in patients receiving an aromatase inhibitor. McVicker and colleagues evaluated the risk for breast cancer–specific mortality in two large female cohorts to determine whether the risk for mortality was higher in women using vaginal estrogen therapy. The analysis included 49,237 women with breast cancer, of which, 5% used vaginal estrogen therapy after a breast cancer diagnosis. Breast cancer–specific mortality was not worsened in patients who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio [HR] 0.77; 95% CI 0.63-0.94). This was also observed when the analysis was restricted to women with hormone-positive breast cancer (HR 0.88; 95% CI 0.62-1.25) or women using aromatase inhibitors (HR 0.72; 95% CI 0.58-0.91). Although, unlike the Danish study, this study did not look at breast cancer recurrence, these findings provide some reassurance that vaginal estrogen therapy can be considered if all other nonhormonal therapies fail to improve genitourinary symptoms. More studies are needed to validate these findings.

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

  1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112
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