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. 2022 Jan;29(1):92-102.
doi: 10.1007/s12282-021-01283-4. Epub 2021 Aug 31.

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: subgroup analysis of the global BREAKOUT study

Su-Jin Koh  1 , Shozo Ohsumi  2 , Masato Takahashi  3 , Eisuke Fukuma  4 , Kyung Hae Jung  5 , Takanori Ishida  6 , Ming-Shen Dai  7 , Chuan-Hsun Chang  8 , Tapashi Dalvi  9 , Graham Walker  10 , James Bennett  10 , Joyce O'Shaughnessy  11 , Judith Balmaña  12
Affiliations

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: subgroup analysis of the global BREAKOUT study

Su-Jin Koh et al. Breast Cancer. 2022 Jan.

Erratum in

Abstract

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.

Keywords: BRCA; Germline mutations; HER2-negative metastatic breast cancer; Homologous recombination repair; Somatic mutations.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Study design. Modified (restructured figure) from Fig. 1 in O’Shaughnessy et al. [12]. Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study. Breast Cancer Research 2020;22:114. Available under a Creative Commons Attribution 4.0 International License. PFS and OS were not assessed due to the early termination of the study. *Blood sample: gBRCA1/2 mutation status was tested using the BRACAnalysis CDx® assay. †Tumor specimen: HRR gene mutations, including sBRCA1/2 and other genomic alterations, were tested using the FoundationOne CDx assay. HER2 human epidermal growth factor receptor 2, HRR homologous recombination repair, MBC metastatic breast cancer, OS overall survival, PFS progression-free survival
Fig. 2
Fig. 2
Patient disposition. Data for the global cohort are reprinted from Fig. 2 in O’Shaughnessy et al. [12]. Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study. Breast Cancer Research 2020;22:114. Available under a Creative Commons Attribution 4.0 International License. FAS full analysis set
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References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Kurian AW, Gong GD, John EM, Miron A, Felberg A, Phipps AI, et al. Performance of prediction models for BRCA mutation carriage in three racial/ethnic groups: findings from the Northern California Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1084–1091. doi: 10.1158/1055-9965.Epi-08-1090. - DOI - PMC - PubMed
    1. Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res. 2006;66(16):8297–8308. doi: 10.1158/0008-5472.Can-06-0503. - DOI - PubMed
    1. Valencia OM, Samuel SE, Viscusi RK, Riall TS, Neumayer LA, Aziz H. The role of genetic testing in patients with breast cancer: a review. JAMA Surg. 2017;152(6):589–594. doi: 10.1001/jamasurg.2017.0552. - DOI - PubMed
    1. Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018;9(1):4083. doi: 10.1038/s41467-018-06581-8. - DOI - PMC - PubMed

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