Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

238P - BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients

Presentation Number
238P
Lecture Time
12:45 - 12:45
Speakers
  • Alex Friedlaender (Geneva, CH)
Location
Hall A3 - Poster Area Networking Hub, ICM M√ľnchen, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

BRCA1 and BRCA2 proteins play a central role in DNA repair process. We hypothesize that BRCA1/BRCA2 germline mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.

Methods

We included women with primary breast cancers treated with (neo)adjuvant chemotherapy and screened for BRCA1/BRCA2 germline mutations 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. None of the patients received dose-dense (every 14 days) chemotherapy. 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. Among patients with triple-negative breast cancers, febrile neutropenia (35% vs. 12%, p = 0.038), grade 3-4 neutropenia (73% vs. 28%, p = 0.003) and grade 4 neutropenia (60% vs. 13%, p = 0.001) were significantly more frequent in BRCA1 carriers compared to non-carriers. Among BRCA1 carriers, the majority of patients were likely to have grade 3-4 neutropenia (88%; p < 0.001), but none of those having mutations located in the RING domain (0%, p = 0.165) compared to 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 three groups.

Conclusions

BRCA1 germline mutations predispose breast cancer patients to greater acute hematological toxicity. This has implication for primary prophylaxis with G-CSF.

Legal entity responsible for the study

Intidhar Labidi-Galy.

Funding

La Fondation Henriette Meyer.

Disclosure

All authors have declared no conflicts of interest.

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