Clinical Edge Journal Scan

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

Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.

The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.

The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.

Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.

Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.

The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.

Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.

Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.

This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.

The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.

This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.

Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.

The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.

The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.

Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.

Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.

The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.

Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.

Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.

This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.

The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.

This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.

Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.

Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.

The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.

The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.

Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.

Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.

The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.

Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.

Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.

This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.

The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.

This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.