BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients.

Abstract

PURPOSE:

BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1/BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.

METHODS:

We included women with primary breast cancers screened for BRCA1/BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3-4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort).

RESULTS:

Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the 3 groups.

CONCLUSIONS:

BRCA1 germline mutations is associated with greater acute hematological toxicity in breast cancer patients. These observations could have implication for primary prophylaxis with G-CSF.

• Authors: Alex Friedlaender, Aurélie Vuilleumier, Valeria Viassolo, Aurélie Ayme, Solène De Talhouet, Jean-Damien Combes, Julien Peron, Alexandre Bodmer, Sophie Giraud, Adrien Buisson, Valerie Bonadona, Isabelle Gauchat-Bouchardy, Olivier Tredan, Pierre O Chappuis, S Intidhar Labidi-Galy
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 174 Issue 3 Pg. 775-783 (Apr 2019) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 30635808 (Publication Type: Journal Article)

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Granulocyte Colony-Stimulating Factor

Topics

• Adult
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Breast Neoplasms (drug therapy, genetics)
• Chemotherapy, Adjuvant (adverse effects)
• Cohort Studies
• Febrile Neutropenia (chemically induced, epidemiology)
• Female
• France
• Germ-Line Mutation
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Hospitalization (statistics & numerical data)
• Humans
• Middle Aged
• Switzerland