Breast Cancer

Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).

Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.

Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.

Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.

Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7

Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).

Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.

Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.

Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.

Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7

Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).

Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.

Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.

Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.

Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.

Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P  =  .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).

Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.

Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P  =  .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).

Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.

Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P  =  .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).

Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423

Key clinical point: Postmastectomy radiotherapy (PMRT) did not influence locoregional recurrence (LRR) in patients with pT1-2 and 1-3 node-positive breast cancer (BC).

Major finding: Rate of LRR at 5 years was similar in patients receiving PMRT and no PMRT (P  =  .61), and PMRT was not significantly associated with LRR in the overall population (P  =  .305).

Study details: Findings are from a retrospective, cohort study including 8914 patients with pT1-2 BC tumors and 1-3 lymph node metastases who received PMRT (n = 492) or no PMRT (n = 8422) after undergoing mastectomy and axillary lymph node dissection.

Disclosures: This study was supported by the Japanese Breast Cancer Society. Some authors declared receiving speaker’s fees, consulting fees, research funds, or honoraria from several sources.

Source: Yamada A et al. Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1–3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry. Eur J Cancer. 2022;172:32-40 (Jun 22). Doi: 10.1016/j.ejca.2022.05.017

Key clinical point: Postmastectomy radiotherapy (PMRT) did not influence locoregional recurrence (LRR) in patients with pT1-2 and 1-3 node-positive breast cancer (BC).

Major finding: Rate of LRR at 5 years was similar in patients receiving PMRT and no PMRT (P  =  .61), and PMRT was not significantly associated with LRR in the overall population (P  =  .305).

Study details: Findings are from a retrospective, cohort study including 8914 patients with pT1-2 BC tumors and 1-3 lymph node metastases who received PMRT (n = 492) or no PMRT (n = 8422) after undergoing mastectomy and axillary lymph node dissection.

Disclosures: This study was supported by the Japanese Breast Cancer Society. Some authors declared receiving speaker’s fees, consulting fees, research funds, or honoraria from several sources.

Source: Yamada A et al. Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1–3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry. Eur J Cancer. 2022;172:32-40 (Jun 22). Doi: 10.1016/j.ejca.2022.05.017

Key clinical point: Postmastectomy radiotherapy (PMRT) did not influence locoregional recurrence (LRR) in patients with pT1-2 and 1-3 node-positive breast cancer (BC).

Major finding: Rate of LRR at 5 years was similar in patients receiving PMRT and no PMRT (P  =  .61), and PMRT was not significantly associated with LRR in the overall population (P  =  .305).

Study details: Findings are from a retrospective, cohort study including 8914 patients with pT1-2 BC tumors and 1-3 lymph node metastases who received PMRT (n = 492) or no PMRT (n = 8422) after undergoing mastectomy and axillary lymph node dissection.

Disclosures: This study was supported by the Japanese Breast Cancer Society. Some authors declared receiving speaker’s fees, consulting fees, research funds, or honoraria from several sources.

Source: Yamada A et al. Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1–3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry. Eur J Cancer. 2022;172:32-40 (Jun 22). Doi: 10.1016/j.ejca.2022.05.017

Key clinical point: Addition of atezolizumab vs placebo to pertuzumab-trastuzumab (PH)+chemotherapy did not improve pathological complete response (pCR) rates in patients with high-risk, human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC).

Major finding: The rate of pCR was similar with atezolizumab and placebo in the intention-to-treat (62.4% and 62.7%, respectively; P  =  .9551) and programmed cell death-ligand 1-positive (64.2% and 72.5%, respectively; P  =  .1846) populations. The atezolizumab vs placebo group reported 5 vs 0 grade 5 adverse events, respectively.

Study details: Findings are from the phase 3 IMpassion050 study including 454 patients with high-risk, HER2+ early BC who were randomly assigned to receive atezolizumab or placebo with PH+chemotherapy in the neoadjuvant setting and continued atezolizumab or placebo with PH in the adjuvant phase.

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd. Six authors declared being employees or stockowners at Roche, and the other authors reported ties with various sources, including Roche.

Source: Huober J et al. Atezolizumab With Neoadjuvant anti–human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2–positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial. J Clin Oncol. 2022 (Jun 28). Doi:  10.1200/JCO.21.02772

Key clinical point: Addition of atezolizumab vs placebo to pertuzumab-trastuzumab (PH)+chemotherapy did not improve pathological complete response (pCR) rates in patients with high-risk, human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC).

Major finding: The rate of pCR was similar with atezolizumab and placebo in the intention-to-treat (62.4% and 62.7%, respectively; P  =  .9551) and programmed cell death-ligand 1-positive (64.2% and 72.5%, respectively; P  =  .1846) populations. The atezolizumab vs placebo group reported 5 vs 0 grade 5 adverse events, respectively.

Study details: Findings are from the phase 3 IMpassion050 study including 454 patients with high-risk, HER2+ early BC who were randomly assigned to receive atezolizumab or placebo with PH+chemotherapy in the neoadjuvant setting and continued atezolizumab or placebo with PH in the adjuvant phase.

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd. Six authors declared being employees or stockowners at Roche, and the other authors reported ties with various sources, including Roche.

Source: Huober J et al. Atezolizumab With Neoadjuvant anti–human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2–positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial. J Clin Oncol. 2022 (Jun 28). Doi:  10.1200/JCO.21.02772

Key clinical point: Addition of atezolizumab vs placebo to pertuzumab-trastuzumab (PH)+chemotherapy did not improve pathological complete response (pCR) rates in patients with high-risk, human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC).

Major finding: The rate of pCR was similar with atezolizumab and placebo in the intention-to-treat (62.4% and 62.7%, respectively; P  =  .9551) and programmed cell death-ligand 1-positive (64.2% and 72.5%, respectively; P  =  .1846) populations. The atezolizumab vs placebo group reported 5 vs 0 grade 5 adverse events, respectively.

Study details: Findings are from the phase 3 IMpassion050 study including 454 patients with high-risk, HER2+ early BC who were randomly assigned to receive atezolizumab or placebo with PH+chemotherapy in the neoadjuvant setting and continued atezolizumab or placebo with PH in the adjuvant phase.

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd. Six authors declared being employees or stockowners at Roche, and the other authors reported ties with various sources, including Roche.

Source: Huober J et al. Atezolizumab With Neoadjuvant anti–human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2–positive early breast cancer: Primary results of the randomized phase III IMpassion050 trial. J Clin Oncol. 2022 (Jun 28). Doi:  10.1200/JCO.21.02772

Key clinical point: The prophylactic use of etoricoxib reduced the incidence and severity of taxane-associated acute pain syndrome (T-APS) and potentially attenuated docetaxel-induced peripheral neuropathy in patients receiving docetaxel-based chemotherapy for breast cancer (BC).

Major finding: Incidence rates of all T-APS (57.1% vs 91.5%) and severe T-APS (11.4% vs 54.9%; both P < .001) were significantly lower in the etoricoxib vs no treatment group. At 3 months follow-up after 4 cycles of docetaxel chemotherapy, the etoricoxib vs no treatment group showed a significantly higher mean Functional Assessment of Cancer Treatment Neurotoxicity subscale score (38.46 vs 34.59; P < .001).

Study details: Findings are from a phase 2 study including 144 adult women with stage I-III BC who received 4 cycles of docetaxel-based chemotherapy and were randomly assigned to receive prophylactic etoricoxib or no treatment.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Zhang J et al. Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: A phase II randomised trial. Eur J Cancer. 2022;171:150-160 (Jun 17). Doi: 10.1016/j.ejca.2022.05.019

Key clinical point: The prophylactic use of etoricoxib reduced the incidence and severity of taxane-associated acute pain syndrome (T-APS) and potentially attenuated docetaxel-induced peripheral neuropathy in patients receiving docetaxel-based chemotherapy for breast cancer (BC).

Major finding: Incidence rates of all T-APS (57.1% vs 91.5%) and severe T-APS (11.4% vs 54.9%; both P < .001) were significantly lower in the etoricoxib vs no treatment group. At 3 months follow-up after 4 cycles of docetaxel chemotherapy, the etoricoxib vs no treatment group showed a significantly higher mean Functional Assessment of Cancer Treatment Neurotoxicity subscale score (38.46 vs 34.59; P < .001).

Study details: Findings are from a phase 2 study including 144 adult women with stage I-III BC who received 4 cycles of docetaxel-based chemotherapy and were randomly assigned to receive prophylactic etoricoxib or no treatment.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Zhang J et al. Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: A phase II randomised trial. Eur J Cancer. 2022;171:150-160 (Jun 17). Doi: 10.1016/j.ejca.2022.05.019

Key clinical point: The prophylactic use of etoricoxib reduced the incidence and severity of taxane-associated acute pain syndrome (T-APS) and potentially attenuated docetaxel-induced peripheral neuropathy in patients receiving docetaxel-based chemotherapy for breast cancer (BC).

Major finding: Incidence rates of all T-APS (57.1% vs 91.5%) and severe T-APS (11.4% vs 54.9%; both P < .001) were significantly lower in the etoricoxib vs no treatment group. At 3 months follow-up after 4 cycles of docetaxel chemotherapy, the etoricoxib vs no treatment group showed a significantly higher mean Functional Assessment of Cancer Treatment Neurotoxicity subscale score (38.46 vs 34.59; P < .001).

Study details: Findings are from a phase 2 study including 144 adult women with stage I-III BC who received 4 cycles of docetaxel-based chemotherapy and were randomly assigned to receive prophylactic etoricoxib or no treatment.

Disclosures: This study was supported by grants from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Zhang J et al. Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: A phase II randomised trial. Eur J Cancer. 2022;171:150-160 (Jun 17). Doi: 10.1016/j.ejca.2022.05.019

Key clinical point: First-line treatment with nivolumab, bevacizumab, and paclitaxel showed promising efficacy with a tolerable safety profile in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC).

Major finding: The objective response rate was 70% (95% CI 55.9%-81.2%) in the overall cohort of patients with HER2-negative metastatic BC, 74% in patients with hormone receptor-positive BC, and 59% in patients with triple-negative BC. Grade 3/4 adverse drug reactions were reported by 58% of patients.

Study details: Findings are primary results from the phase 2 NEWBEAT study including 57 women with invasive, metastatic, or inoperable HER2-negative BC who received the first-line triple therapy with nivolumab, bevacizumab, and paclitaxel.

Disclosures: This study was supported by Ono Pharmaceutical Company. The authors declared receiving research funds, grants, personal fees, lecture fees, honoraria, or consulting fees from several sources, including Ono Pharmaceuticals.

Source: Ozaki Y et al. Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B). Eur J Cancer. 2022;171:193-202 (Jun 18). Doi: 10.1016/j.ejca.2022.05.014

Key clinical point: First-line treatment with nivolumab, bevacizumab, and paclitaxel showed promising efficacy with a tolerable safety profile in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC).

Major finding: The objective response rate was 70% (95% CI 55.9%-81.2%) in the overall cohort of patients with HER2-negative metastatic BC, 74% in patients with hormone receptor-positive BC, and 59% in patients with triple-negative BC. Grade 3/4 adverse drug reactions were reported by 58% of patients.

Study details: Findings are primary results from the phase 2 NEWBEAT study including 57 women with invasive, metastatic, or inoperable HER2-negative BC who received the first-line triple therapy with nivolumab, bevacizumab, and paclitaxel.

Disclosures: This study was supported by Ono Pharmaceutical Company. The authors declared receiving research funds, grants, personal fees, lecture fees, honoraria, or consulting fees from several sources, including Ono Pharmaceuticals.

Source: Ozaki Y et al. Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B). Eur J Cancer. 2022;171:193-202 (Jun 18). Doi: 10.1016/j.ejca.2022.05.014

Key clinical point: First-line treatment with nivolumab, bevacizumab, and paclitaxel showed promising efficacy with a tolerable safety profile in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC).

Major finding: The objective response rate was 70% (95% CI 55.9%-81.2%) in the overall cohort of patients with HER2-negative metastatic BC, 74% in patients with hormone receptor-positive BC, and 59% in patients with triple-negative BC. Grade 3/4 adverse drug reactions were reported by 58% of patients.

Study details: Findings are primary results from the phase 2 NEWBEAT study including 57 women with invasive, metastatic, or inoperable HER2-negative BC who received the first-line triple therapy with nivolumab, bevacizumab, and paclitaxel.

Disclosures: This study was supported by Ono Pharmaceutical Company. The authors declared receiving research funds, grants, personal fees, lecture fees, honoraria, or consulting fees from several sources, including Ono Pharmaceuticals.

Source: Ozaki Y et al. Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B). Eur J Cancer. 2022;171:193-202 (Jun 18). Doi: 10.1016/j.ejca.2022.05.014

Key clinical point: The risk for hemorrhage was not significantly different in patients with breast cancer (BC) aged ≥ 66 years who received direct oral anticoagulants (DOAC) concurrently with tamoxifen vs aromatase inhibitors (AI).

Major finding: During a median follow-up of 166 days, the risk for major hemorrhage requiring an emergency department visit or hospitalization (2.5% vs 3.3%; weighted hazard ratio [HR] 0.68; 95% CI 0.44-1.06) or any hemorrhage (4.9% vs 4.6%; weighted HR 1.04; 95% CI 0.75-1.43) was not higher with tamoxifen+DOAC compared with AI+DOAC.

Study details: Findings are from a population-based, retrospective cohort study including 4753 patients aged ≥ 66 years with BC who were prescribed tamoxifen or AI concurrently with a DOAC.

Disclosures: This study was supported by Canadian Institutes of Health Research and ICES. Some authors declared serving on advisory boards of or receiving grants, personal fees, or travel expenses from several sources.

Source: Wang T-F et al. Hemorrhage risk among patients with breast cancer receiving concurrent direct oral anticoagulants with tamoxifen vs aromatase inhibitors. JAMA Netw Open. 2022;5(6):e2219128 (Jun 28). Doi: 10.1001/jamanetworkopen.2022.19128

Key clinical point: The risk for hemorrhage was not significantly different in patients with breast cancer (BC) aged ≥ 66 years who received direct oral anticoagulants (DOAC) concurrently with tamoxifen vs aromatase inhibitors (AI).

Major finding: During a median follow-up of 166 days, the risk for major hemorrhage requiring an emergency department visit or hospitalization (2.5% vs 3.3%; weighted hazard ratio [HR] 0.68; 95% CI 0.44-1.06) or any hemorrhage (4.9% vs 4.6%; weighted HR 1.04; 95% CI 0.75-1.43) was not higher with tamoxifen+DOAC compared with AI+DOAC.

Study details: Findings are from a population-based, retrospective cohort study including 4753 patients aged ≥ 66 years with BC who were prescribed tamoxifen or AI concurrently with a DOAC.

Disclosures: This study was supported by Canadian Institutes of Health Research and ICES. Some authors declared serving on advisory boards of or receiving grants, personal fees, or travel expenses from several sources.

Source: Wang T-F et al. Hemorrhage risk among patients with breast cancer receiving concurrent direct oral anticoagulants with tamoxifen vs aromatase inhibitors. JAMA Netw Open. 2022;5(6):e2219128 (Jun 28). Doi: 10.1001/jamanetworkopen.2022.19128

Key clinical point: The risk for hemorrhage was not significantly different in patients with breast cancer (BC) aged ≥ 66 years who received direct oral anticoagulants (DOAC) concurrently with tamoxifen vs aromatase inhibitors (AI).

Major finding: During a median follow-up of 166 days, the risk for major hemorrhage requiring an emergency department visit or hospitalization (2.5% vs 3.3%; weighted hazard ratio [HR] 0.68; 95% CI 0.44-1.06) or any hemorrhage (4.9% vs 4.6%; weighted HR 1.04; 95% CI 0.75-1.43) was not higher with tamoxifen+DOAC compared with AI+DOAC.

Study details: Findings are from a population-based, retrospective cohort study including 4753 patients aged ≥ 66 years with BC who were prescribed tamoxifen or AI concurrently with a DOAC.

Disclosures: This study was supported by Canadian Institutes of Health Research and ICES. Some authors declared serving on advisory boards of or receiving grants, personal fees, or travel expenses from several sources.

Source: Wang T-F et al. Hemorrhage risk among patients with breast cancer receiving concurrent direct oral anticoagulants with tamoxifen vs aromatase inhibitors. JAMA Netw Open. 2022;5(6):e2219128 (Jun 28). Doi: 10.1001/jamanetworkopen.2022.19128

Key clinical point: Digital breast tomosynthesis (DBT) reduced the likelihood of advanced breast cancer (BC) diagnosis compared with digital mammography in women with extremely dense breasts and a high risk for BC.

Major finding: Overall screening outcomes per 1000 examinations were similar with DBT vs digital mammography for interval invasive cancer (difference −0.04; 95% CI −0.14 to 0.06); however, the advanced cancer detection rate was lower in women with extremely dense breasts and a high BC risk (difference −0.53; 95% CI −0.97 to −0.10).

Study details: Findings are from a cohort study including 504,427 women with no history of BC or mastectomy who underwent 1,003,900 digital mammography screening examinations or 374,002 DBT screening examinations.

Disclosures: This study was funded by Patient-Centered Outcomes Research Institute, National Cancer Institute, and other sources. Some authors declared receiving grants, consulting fees, or royalties from or serving as consultants or on the editorial board for several sources.

Source: Kerlikowske K et al. Association of screening with digital breast tomosynthesis vs digital mammography with risk of interval invasive and advanced breast cancer. JAMA. 2022;327(22):2220–2230 (Jun 14). Doi: 10.1001/jama.2022.7672

Key clinical point: Digital breast tomosynthesis (DBT) reduced the likelihood of advanced breast cancer (BC) diagnosis compared with digital mammography in women with extremely dense breasts and a high risk for BC.

Major finding: Overall screening outcomes per 1000 examinations were similar with DBT vs digital mammography for interval invasive cancer (difference −0.04; 95% CI −0.14 to 0.06); however, the advanced cancer detection rate was lower in women with extremely dense breasts and a high BC risk (difference −0.53; 95% CI −0.97 to −0.10).

Study details: Findings are from a cohort study including 504,427 women with no history of BC or mastectomy who underwent 1,003,900 digital mammography screening examinations or 374,002 DBT screening examinations.

Disclosures: This study was funded by Patient-Centered Outcomes Research Institute, National Cancer Institute, and other sources. Some authors declared receiving grants, consulting fees, or royalties from or serving as consultants or on the editorial board for several sources.

Source: Kerlikowske K et al. Association of screening with digital breast tomosynthesis vs digital mammography with risk of interval invasive and advanced breast cancer. JAMA. 2022;327(22):2220–2230 (Jun 14). Doi: 10.1001/jama.2022.7672

Key clinical point: Digital breast tomosynthesis (DBT) reduced the likelihood of advanced breast cancer (BC) diagnosis compared with digital mammography in women with extremely dense breasts and a high risk for BC.

Major finding: Overall screening outcomes per 1000 examinations were similar with DBT vs digital mammography for interval invasive cancer (difference −0.04; 95% CI −0.14 to 0.06); however, the advanced cancer detection rate was lower in women with extremely dense breasts and a high BC risk (difference −0.53; 95% CI −0.97 to −0.10).

Study details: Findings are from a cohort study including 504,427 women with no history of BC or mastectomy who underwent 1,003,900 digital mammography screening examinations or 374,002 DBT screening examinations.

Disclosures: This study was funded by Patient-Centered Outcomes Research Institute, National Cancer Institute, and other sources. Some authors declared receiving grants, consulting fees, or royalties from or serving as consultants or on the editorial board for several sources.

Source: Kerlikowske K et al. Association of screening with digital breast tomosynthesis vs digital mammography with risk of interval invasive and advanced breast cancer. JAMA. 2022;327(22):2220–2230 (Jun 14). Doi: 10.1001/jama.2022.7672

Key clinical point: Trastuzumab deruxtecan vs physician’s choice of chemotherapy reduced the risk for disease progression or death by ~50% in previously treated patients with human epidermal growth factor receptor-2 (HER2)-low metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs chemotherapy significantly improved the median progression-free survival in the overall cohort of patients (hazard ratio for disease progression/death [HR] 0.50; P < .001), irrespective of the hormone-receptor status (positive: HR 0.51; P < .001, or negative: HR 0.46; 95% CI 0.24-0.89). The incidence of grade ≥3 adverse events was 52.6% with trastuzumab deruxtecan and 67.4% with chemotherapy.

Study details: Findings are from the phase 3 DESTINY-Breast04 study including 557 patients with HER2-low metastatic BC who were previously treated with 1 or 2 lines of chemotherapy and were randomly assigned to receive trastuzumab deruxtecan or physician’s choice of chemotherapy.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including AstraZeneca and Daiichi Sankyo.

Source: Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9-20 (Jun 5). Doi: 10.1056/NEJMoa2203690

Key clinical point: Trastuzumab deruxtecan vs physician’s choice of chemotherapy reduced the risk for disease progression or death by ~50% in previously treated patients with human epidermal growth factor receptor-2 (HER2)-low metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs chemotherapy significantly improved the median progression-free survival in the overall cohort of patients (hazard ratio for disease progression/death [HR] 0.50; P < .001), irrespective of the hormone-receptor status (positive: HR 0.51; P < .001, or negative: HR 0.46; 95% CI 0.24-0.89). The incidence of grade ≥3 adverse events was 52.6% with trastuzumab deruxtecan and 67.4% with chemotherapy.

Study details: Findings are from the phase 3 DESTINY-Breast04 study including 557 patients with HER2-low metastatic BC who were previously treated with 1 or 2 lines of chemotherapy and were randomly assigned to receive trastuzumab deruxtecan or physician’s choice of chemotherapy.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including AstraZeneca and Daiichi Sankyo.

Source: Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9-20 (Jun 5). Doi: 10.1056/NEJMoa2203690

Key clinical point: Trastuzumab deruxtecan vs physician’s choice of chemotherapy reduced the risk for disease progression or death by ~50% in previously treated patients with human epidermal growth factor receptor-2 (HER2)-low metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs chemotherapy significantly improved the median progression-free survival in the overall cohort of patients (hazard ratio for disease progression/death [HR] 0.50; P < .001), irrespective of the hormone-receptor status (positive: HR 0.51; P < .001, or negative: HR 0.46; 95% CI 0.24-0.89). The incidence of grade ≥3 adverse events was 52.6% with trastuzumab deruxtecan and 67.4% with chemotherapy.

Study details: Findings are from the phase 3 DESTINY-Breast04 study including 557 patients with HER2-low metastatic BC who were previously treated with 1 or 2 lines of chemotherapy and were randomly assigned to receive trastuzumab deruxtecan or physician’s choice of chemotherapy.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including AstraZeneca and Daiichi Sankyo.

Source: Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9-20 (Jun 5). Doi: 10.1056/NEJMoa2203690

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.