TY - JOUR
T1 - Prevalence of mutations in BRCA and homologous recombination repair genes and real-world standard of care of Asian patients with HER2-negative metastatic breast cancer starting first-line systemic cytotoxic chemotherapy
T2 - subgroup analysis of the global BREAKOUT study
AU - Koh, Su Jin
AU - Ohsumi, Shozo
AU - Takahashi, Masato
AU - Fukuma, Eisuke
AU - Jung, Kyung Hae
AU - Ishida, Takanori
AU - Dai, Ming Shen
AU - Chang, Chuan Hsun
AU - Dalvi, Tapashi
AU - Walker, Graham
AU - Bennett, James
AU - O’Shaughnessy, Joyce
AU - Balmaña, Judith
N1 - Funding Information:
The authors thank Nicholas D. Smith (EMC K.K.) for medical writing support, which was funded by AstraZeneca.
Funding Information:
Shozo Ohsumi and Takanori Ishida have received honoraria for lecture fees from AstraZeneca. Kyung Hae Jung has received consultancy fees from AstraZeneca, Celgene, Eisai, Novartis, and Roche. Masato Takahashi has received honoraria for lecture fees from AstraZeneca, Eisai, Eli Lilly, and Pfizer. Tapashi Dalvi, Graham Walker, and James Bennett are employees or contracted employees of AstraZeneca and may own stock. Joyce O’Shaughnessy has received honoraria for consulting and advisory boards from AbbVie, Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai, Eli Lilly, Genentech, Genomic Health, GRAIL, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Merck, Myriad, Novartis, Odonate Therapeutics, Pfizer, Puma Biotechnology, Roche, Seattle Genetics, and Syndax Pharmaceuticals. Judith Balmaña has received honoraria for consultancy from AstraZeneca, PharmaMar, and Pfizer, and research support from AstraZeneca and PharmaMar. Su-Jin Koh, Eisuke Fukuma, Ming-Shen Dai, and Chuan-Hsun Chang have nothing to declare.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/1
Y1 - 2022/1
N2 - Background: The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. Methods: Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). Results: Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25–87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. Conclusion: We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC. Study registration: NCT03078036.
AB - Background: The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. Methods: Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). Results: Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25–87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. Conclusion: We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC. Study registration: NCT03078036.
KW - BRCA
KW - Germline mutations
KW - HER2-negative metastatic breast cancer
KW - Homologous recombination repair
KW - Somatic mutations
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U2 - 10.1007/s12282-021-01283-4
DO - 10.1007/s12282-021-01283-4
M3 - Article
C2 - 34467476
AN - SCOPUS:85113992207
VL - 29
SP - 92
EP - 102
JO - Breast Cancer
JF - Breast Cancer
SN - 1340-6868
IS - 1
ER -