Hematologic toxicity in BRCA1 and BRCA2 mutation carriers during chemotherapy: A retrospective matched cohort study

• Published in: Cancer medicine (Malden, MA) MA), 2019-09, Vol.8 (12), p.5609-5618
• Main Authors: West, Allison H., Knollman, Hayley, Dugan, James, Hedeker, Donald, Handorf, Elisabeth A., Nielsen, Sarah M., Bealin, Lisa C., Goldblatt, Lindsay G., Willems, Heather, Daly, Mary B., Afghahi, Anosheh, Olopade, Olufunmilayo I., Hulick, Peter J., Shagisultanova, Elena, Huo, Dezheng, Obeid, Elias, Churpek, Jane E.
• Format: Article
• Language: English
• Subjects: Adult; Age; Blood tests; Bone marrow; BRCA1; BRCA1 protein; BRCA1 Protein - genetics; BRCA2; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer therapies; Case-Control Studies; Chemotherapy; Clinical Cancer Research; Cohort analysis; Cytotoxicity; Data analysis; Deoxyribonucleic acid; DNA; DNA repair; Editing; Female; Funding; Genetic disorders; Germ-Line Mutation; Haploinsufficiency; hematologic toxicity; Hemoglobin; hereditary breast and ovarian cancer syndrome; Humans; Middle Aged; Mutation; Neutropenia; neutropenic fever; Original Research; Ovarian cancer; Patients; Retrospective Studies; Studies; Supervision; Survival Analysis; Treatment Outcome; Variables
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2471

Women who inherit a BRCA1 or BRCA2 mutation have an increased risk of breast cancer. Preliminary evidence suggests they may also have defects in bone marrow function. To test this hypothesis, we conducted a multicenter, retrospective, matched cohort study, comparing women with localized breast cancer requiring cytotoxic chemotherapy who carried an inherited BRCA1 or BRCA2 mutation to similar wild‐type patients treated between 1995 and 2017 and matched based on age, race, site, and chemotherapy regimen. The proportion who developed specific hematologic toxicities, timing of these toxicities, and patterns of blood count fluctuations over time were compared among BRCA1 carriers vs matched wild‐type patients and among BRCA2 carriers vs matched wild‐type patients. 88 BRCA1 carriers and 75 BRCA2 carriers were matched to 226 and 242 wild‐type patients, respectively. The proportions and timing of experiencing any grade or grade 3/4 cytopenias during chemotherapy were not significantly different for BRCA1 carriers or BRCA2 carriers vs matched wild‐type patients. Proportions requiring treatment modifications and time to first modification were also similar. Patterns of blood count fluctuations over time in mutation carriers mirrored those in wild‐type patients overall and by the most common regimens. Women with an inherited mutation in BRCA1 or BRCA2 experience similar frequency, severity, and timing of hematologic toxicities during curative intent breast cancer chemotherapy as matched wild‐type patients. Our findings suggest that BRCA1 or BRCA2 haploinsufficiency is sufficient for adequate bone marrow reserve in the face of short‐term repetitive hematopoietic stressors. In this multicenter, retrospective, matched cohort study, we investigated whether women with an inherited mutation in BRCA1 or BRCA2 experience more severe hematologic toxicities during curative intent chemotherapy for breast cancer than similar women without a mutation. We found that the frequency, severity, and timing of toxicities were similar in these two groups. This study is reassuring that women with an inherited mutation are able to tolerate the repetitive bone marrow stress of modern chemotherapy regimens with usual supportive care measures as well as those without a mutation.