Clinical Edge Journal Scan

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low vs HER2-0 expression was associated with improved breast cancer-specific survival (BCSS) outcomes in patients with early-stage triple-negative breast cancer (TNBC), particularly in the high-risk subgroups.

Major finding: Patients with HER2-low vs HER2-0 BC had significantly better BCSS rates in the overall population (96.6% vs 93.7%; log-rank P = .027) and in high-risk subpopulations comprising patients without a pathological complete response despite neoadjuvant chemotherapy (log-rank P = .047) or those with stage-III BC (log-rank P = .010).

Study details: Findings are from a study including 1445 female patients with early-stage TNBC, of whom 51.7% and 48.3% showed HER2-0 and HER2-low status, respectively.

Disclosures: This study was sponsored by the Health Commission of Henan Province, China. The authors declared no conflicts of interest.

Source: Ma Y et al. HER2-low status was associated with better breast cancer-specific survival in early-stage triple-negative breast cancer. Oncologist. 2023 (Sep 28). doi: 10.1093/oncolo/oyad275

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low vs HER2-0 expression was associated with improved breast cancer-specific survival (BCSS) outcomes in patients with early-stage triple-negative breast cancer (TNBC), particularly in the high-risk subgroups.

Major finding: Patients with HER2-low vs HER2-0 BC had significantly better BCSS rates in the overall population (96.6% vs 93.7%; log-rank P = .027) and in high-risk subpopulations comprising patients without a pathological complete response despite neoadjuvant chemotherapy (log-rank P = .047) or those with stage-III BC (log-rank P = .010).

Study details: Findings are from a study including 1445 female patients with early-stage TNBC, of whom 51.7% and 48.3% showed HER2-0 and HER2-low status, respectively.

Disclosures: This study was sponsored by the Health Commission of Henan Province, China. The authors declared no conflicts of interest.

Source: Ma Y et al. HER2-low status was associated with better breast cancer-specific survival in early-stage triple-negative breast cancer. Oncologist. 2023 (Sep 28). doi: 10.1093/oncolo/oyad275

Key clinical point: Human epidermal growth factor receptor 2 (HER2)-low vs HER2-0 expression was associated with improved breast cancer-specific survival (BCSS) outcomes in patients with early-stage triple-negative breast cancer (TNBC), particularly in the high-risk subgroups.

Major finding: Patients with HER2-low vs HER2-0 BC had significantly better BCSS rates in the overall population (96.6% vs 93.7%; log-rank P = .027) and in high-risk subpopulations comprising patients without a pathological complete response despite neoadjuvant chemotherapy (log-rank P = .047) or those with stage-III BC (log-rank P = .010).

Study details: Findings are from a study including 1445 female patients with early-stage TNBC, of whom 51.7% and 48.3% showed HER2-0 and HER2-low status, respectively.

Disclosures: This study was sponsored by the Health Commission of Henan Province, China. The authors declared no conflicts of interest.

Source: Ma Y et al. HER2-low status was associated with better breast cancer-specific survival in early-stage triple-negative breast cancer. Oncologist. 2023 (Sep 28). doi: 10.1093/oncolo/oyad275

Key clinical point: This real-world study confirmed the effectiveness of tucatinib across all treatment lines in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Median real-world time-to-treatment discontinuation was 6.5 months (95% CI 5.4-8.8 months) for the overall population but was longer in patients who received tucatinib in combination with trastuzumab and capecitabine in a metastatic setting (8.1 months; 95% CI 5.7-9.5 months) or as second-line or third-line therapy (9.4 months; 95% CI 6.3-14.1 months). Median real-world overall survival was 26.6 months (95% CI 20.2-not reached).

Study details: Findings are from a retrospective cohort study including 216 patients with HER2+ metastatic BC who received tucatinib in any line of therapy.

Disclosures: This study was sponsored by Seagen Inc. and Merck Sharp & Dohme LLC. Seven authors declared being employees of and holding stock or stock options in Seagen Inc., and the other authors declared ties with various sources, including Seagen and Merck Sharp & Dohme.

Source: Kaufman PA et al. Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer. Front Oncol. 2023;13:1264861 (Oct 2). doi: 10.3389/fonc.2023.1264861

Key clinical point: This real-world study confirmed the effectiveness of tucatinib across all treatment lines in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Median real-world time-to-treatment discontinuation was 6.5 months (95% CI 5.4-8.8 months) for the overall population but was longer in patients who received tucatinib in combination with trastuzumab and capecitabine in a metastatic setting (8.1 months; 95% CI 5.7-9.5 months) or as second-line or third-line therapy (9.4 months; 95% CI 6.3-14.1 months). Median real-world overall survival was 26.6 months (95% CI 20.2-not reached).

Study details: Findings are from a retrospective cohort study including 216 patients with HER2+ metastatic BC who received tucatinib in any line of therapy.

Disclosures: This study was sponsored by Seagen Inc. and Merck Sharp & Dohme LLC. Seven authors declared being employees of and holding stock or stock options in Seagen Inc., and the other authors declared ties with various sources, including Seagen and Merck Sharp & Dohme.

Source: Kaufman PA et al. Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer. Front Oncol. 2023;13:1264861 (Oct 2). doi: 10.3389/fonc.2023.1264861

Key clinical point: This real-world study confirmed the effectiveness of tucatinib across all treatment lines in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Median real-world time-to-treatment discontinuation was 6.5 months (95% CI 5.4-8.8 months) for the overall population but was longer in patients who received tucatinib in combination with trastuzumab and capecitabine in a metastatic setting (8.1 months; 95% CI 5.7-9.5 months) or as second-line or third-line therapy (9.4 months; 95% CI 6.3-14.1 months). Median real-world overall survival was 26.6 months (95% CI 20.2-not reached).

Study details: Findings are from a retrospective cohort study including 216 patients with HER2+ metastatic BC who received tucatinib in any line of therapy.

Disclosures: This study was sponsored by Seagen Inc. and Merck Sharp & Dohme LLC. Seven authors declared being employees of and holding stock or stock options in Seagen Inc., and the other authors declared ties with various sources, including Seagen and Merck Sharp & Dohme.

Source: Kaufman PA et al. Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer. Front Oncol. 2023;13:1264861 (Oct 2). doi: 10.3389/fonc.2023.1264861

Key clinical point: Unlike partial breast irradiation (PBI), intraoperative radiation therapy (IORT) was associated with higher ipsilateral breast tumor recurrence (IBTR) rates than whole breast irradiation (WBI) in patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: The risk for IBTR was comparable in patients treated with PBI and WBI (hazard ratio [HR] 1.20; P = .12) but was significantly higher in patients treated with IORT vs WBI (HR 1.46; P < .01).

Study details: Findings are from a meta-analysis of 11 randomized controlled trials including 15,460 patients with early-stage BC who underwent BCS, of whom 7190 patients, 4931 patients, and 2372 patients received WBI, PBI, and IORT, respectively.

Disclosures: This study did not receive any specific funding. Some authors declared serving as consultants for or receiving grants from various sources.

Source: Ravani LV et al. Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: A Kaplan-Meier-derived patient data meta-analysis. Breast Cancer Res Treat. 2023 (Sep 22). doi: 10.1007/s10549-023-07112-w

Key clinical point: Unlike partial breast irradiation (PBI), intraoperative radiation therapy (IORT) was associated with higher ipsilateral breast tumor recurrence (IBTR) rates than whole breast irradiation (WBI) in patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: The risk for IBTR was comparable in patients treated with PBI and WBI (hazard ratio [HR] 1.20; P = .12) but was significantly higher in patients treated with IORT vs WBI (HR 1.46; P < .01).

Study details: Findings are from a meta-analysis of 11 randomized controlled trials including 15,460 patients with early-stage BC who underwent BCS, of whom 7190 patients, 4931 patients, and 2372 patients received WBI, PBI, and IORT, respectively.

Disclosures: This study did not receive any specific funding. Some authors declared serving as consultants for or receiving grants from various sources.

Source: Ravani LV et al. Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: A Kaplan-Meier-derived patient data meta-analysis. Breast Cancer Res Treat. 2023 (Sep 22). doi: 10.1007/s10549-023-07112-w

Key clinical point: Unlike partial breast irradiation (PBI), intraoperative radiation therapy (IORT) was associated with higher ipsilateral breast tumor recurrence (IBTR) rates than whole breast irradiation (WBI) in patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS).

Major finding: The risk for IBTR was comparable in patients treated with PBI and WBI (hazard ratio [HR] 1.20; P = .12) but was significantly higher in patients treated with IORT vs WBI (HR 1.46; P < .01).

Study details: Findings are from a meta-analysis of 11 randomized controlled trials including 15,460 patients with early-stage BC who underwent BCS, of whom 7190 patients, 4931 patients, and 2372 patients received WBI, PBI, and IORT, respectively.

Disclosures: This study did not receive any specific funding. Some authors declared serving as consultants for or receiving grants from various sources.

Source: Ravani LV et al. Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: A Kaplan-Meier-derived patient data meta-analysis. Breast Cancer Res Treat. 2023 (Sep 22). doi: 10.1007/s10549-023-07112-w

Key clinical point: Compared with good or low adherence to adjuvant hormone therapy (HT), excellent adherence was associated with a significantly reduced risk for subsequent breast tumors (SBT) in older women with ductal carcinoma in situ (DCIS) of the breast.

Major finding: In patients with excellent vs low adherence to adjuvant HT, both breast-conserving surgery (BCS) and BCS + radiation therapy (RT) significantly reduced the risks for SBT (−10.54 and −6.24 percentage points, respectively; both P < .00001) or subsequent invasive breast cancer (−8.85 and −4.28 percentage points, respectively; both P < .00001). Similar results were obtained in patients with excellent vs good adherence to adjuvant HT.

Study details: Findings are from an analysis of a population-based study including 3075 women with DCIS who were age ≥ 65 years and underwent BCS either with (75%) or without RT (25%).

Disclosures: This study was supported by the US National Cancer Institute. Two authors declared serving as consultants for various sources.

Source: Mitchell JM et al. Adherence to hormonal therapy after surgery among older women with ductal carcinoma in situ: Implications for breast cancer-related adverse health events. Cancer. 2023 (Sep 26). Doi: 10.1002/cncr.35009

Key clinical point: Compared with good or low adherence to adjuvant hormone therapy (HT), excellent adherence was associated with a significantly reduced risk for subsequent breast tumors (SBT) in older women with ductal carcinoma in situ (DCIS) of the breast.

Major finding: In patients with excellent vs low adherence to adjuvant HT, both breast-conserving surgery (BCS) and BCS + radiation therapy (RT) significantly reduced the risks for SBT (−10.54 and −6.24 percentage points, respectively; both P < .00001) or subsequent invasive breast cancer (−8.85 and −4.28 percentage points, respectively; both P < .00001). Similar results were obtained in patients with excellent vs good adherence to adjuvant HT.

Study details: Findings are from an analysis of a population-based study including 3075 women with DCIS who were age ≥ 65 years and underwent BCS either with (75%) or without RT (25%).

Disclosures: This study was supported by the US National Cancer Institute. Two authors declared serving as consultants for various sources.

Source: Mitchell JM et al. Adherence to hormonal therapy after surgery among older women with ductal carcinoma in situ: Implications for breast cancer-related adverse health events. Cancer. 2023 (Sep 26). Doi: 10.1002/cncr.35009

Key clinical point: Compared with good or low adherence to adjuvant hormone therapy (HT), excellent adherence was associated with a significantly reduced risk for subsequent breast tumors (SBT) in older women with ductal carcinoma in situ (DCIS) of the breast.

Major finding: In patients with excellent vs low adherence to adjuvant HT, both breast-conserving surgery (BCS) and BCS + radiation therapy (RT) significantly reduced the risks for SBT (−10.54 and −6.24 percentage points, respectively; both P < .00001) or subsequent invasive breast cancer (−8.85 and −4.28 percentage points, respectively; both P < .00001). Similar results were obtained in patients with excellent vs good adherence to adjuvant HT.

Study details: Findings are from an analysis of a population-based study including 3075 women with DCIS who were age ≥ 65 years and underwent BCS either with (75%) or without RT (25%).

Disclosures: This study was supported by the US National Cancer Institute. Two authors declared serving as consultants for various sources.

Source: Mitchell JM et al. Adherence to hormonal therapy after surgery among older women with ductal carcinoma in situ: Implications for breast cancer-related adverse health events. Cancer. 2023 (Sep 26). Doi: 10.1002/cncr.35009

Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: Prophylactic salpingo-oophorectomy (PSO) after breast surgery leads to significantly improved overall survival (OS) outcomes and can be considered in patients with BRCA1/2 breast cancer (BC), particularly in those with the BRCA1 variant.

Major finding: Patients who did vs did not undergo PSO had significantly improved OS outcomes in the overall population (hazard ratio [HR] 0.40; P < .001) and in subgroups of patients with BRCA1 BC (HR 0.35;  95% CI 0.20-0.63), triple-negative BC (HR 0.21;  95% CI 0.09-0.46), and invasive ductal carcinoma (HR 0.51;  95% CI 0.31-0.84).

Study details: Findings are from a retrospective cohort study including 480 patients with BRCA1 (n = 290) or BRCA2 (n = 190) BC who underwent surgical resection, of whom 300 and 163 patients underwent PSO and prophylactic mastectomy, respectively.

Disclosures: This study did not disclose any funding source. Two authors declared being advisory board members of or receiving grants or personal fees from various sources unrelated to this study.

Source: Martelli G et al. Prophylactic salpingo-oophorectomy and survival after BRCA1/2 breast cancer resection. JAMA Surg. 2023 (Oct 4). doi: 10.1001/jamasurg.2023.4770

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: The development of contralateral breast cancer (CBC) was associated with worsened survival outcomes if the primary breast cancer (PBC) subtype was hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−) or if the patients had CBC onset within 1.5 years after PBC surgery.

Major finding: Compared with patients who did not develop CBC, the risk for death was higher in patients who developed CBC within 1.5 years after PBC surgery (hazard ratio 2.014; P = .04) and in those with HR+/ERBB2− PBC (hazard ratio 1.882; P = .01).

Study details: Findings are from a cohort study including 16,251 patients with stages 0-III PBC, of whom 418 patients developed CBC.

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

Source: Kim H et al. Survival after development of contralateral breast cancer in Korean patients with breast cancer. JAMA Netw Open. 2023;6(9):e2333557 (Sep 14). doi: 10.1001/jamanetworkopen.2023.33557

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who were exposed to fine particulate matter, ie, airborne particles with an aerodynamic diameter ≤ 2.5 μm (PM_2.5), showed an increased risk of developing breast cancer (BC), particularly estrogen receptor-positive (ER+) BC.

Major finding: As little as a 10 µg/m³ increase in PM_2.5 concentration during 1980-1984 increased the incident risk for BC by 8% (hazard ratio [HR] 1.08;  95% CI 1.02-1.13), with the risk being even higher in case of ER+ BC (HR 1.10;  95% CI 1.04-1.17).

Study details: Findings are from an analysis of a prospective, US-based cohort including 196,905 women with no prior history of cancer, of whom 15,870 developed incident BC.

Disclosures: This study was funded by the US National Institutes of Environmental Health Sciences and the US National Cancer Institute Intramural Program. The authors declared no conflicts of interest.

Source: White AJ et al. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort. J Natl Cancer Inst. 2023 (Sep 11). doi: 10.1093/jnci/djad170

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: Women who survived cancer during childhood and received ≥ 200 mg/m² cumulative doxorubicin dose as a part of the treatment may have an increased risk of developing subsequent breast cancer (SBC).

Major finding: A ≥200 mg/m² cumulative doxorubicin dose vs no doxorubicin treatment led to > 2-fold increase in the risk for SBC (hazard ratio [HR] for 200-299  mg/m²: 2.50, 95% CI 1.85-3.40; HR for 300-399  mg/m²: 2.33, 95% CI 1.68-3.23; and HR for ≥ 400  mg/m²: 2.78, 95% CI 1.99-3.88). Every 100 mg/m² increase in the cumulative doxorubicin dose increased SBC risk in patients who survived cancer and either received (HR 1.11;  95% CI 1.02-1.21) or did not receive chest radiotherapy (HR 1.26;  95% CI 1.17-1.36).

<Study details: Findings are from an analysis of a pooled cohort including 17,903 females who survived cancer for ≥ 5 years, of whom 782 survivors developed SBC.

Disclosures: This study was supported by the Children Cancer Free Foundation (aka Foundation KiKa, Stichting Kinderen Kankervrij), Amsterdam. The authors declared no conflicts of interest.

Source: Wang Y et al for The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer. Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer. Nat Med. 2023;29(9):2268-2277 (Sep 11). doi: 10.1038/s41591-023-02514-1

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

Key clinical point: The omission of axillary surgery leads to non-inferior outcomes compared to sentinel lymph node biopsy (SLNB) and may not be necessary in patients with early breast cancer (BC) having a tumor diameter ≤ 2 cm and negative results for preoperative axillary lymph node ultrasonography.

Major finding: The rates of 5-year distant disease-free survival were comparable in patients who underwent SLNB and those who did not undergo axillary surgery (97.7% vs 98.0%; hazard ratio 0.84; noninferiority P = .02).

Study details: Findings are from the phase 3 SOUND trial including 1405 women with BC having a tumor diameter ≤ 2 cm and negative preoperative axillary ultrasonography results who were randomly assigned to undergo either SLNB or no axillary surgery.

Disclosures: This study did not disclose any funding source. Some authors declared receiving personal fees from various sources.

Source: Gentilini OD et al for the SOUND Trial Group. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023 (Sep 21). doi: 10.1001/jamaoncol.2023.3759

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.