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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

3393 - BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients

Date

22 Oct 2018

Session

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

Presenters

Alex Friedlaender

Citation

Annals of Oncology (2018) 29 (suppl_8): viii58-viii86. 10.1093/annonc/mdy270

Authors

A. Friedlaender1, A. Vuillemier1, V. Viassolo1, A. Ayme2, S. De Talhouet3, J. Combes4, J. Peron5, A. Bodmer1, S. Giraud6, A. Buisson6, V. Bonadona7, I. Gauchat-Bouchardy8, O. Tredan9, P. Chappuis10, S.I. Labidi-Galy10

Author affiliations

  • 1 Department Of Oncology, Hopitaux Universitaires de Geneve, 1205 - Geneva/CH
  • 2 Department Of Genetics, Hopitaux Universitaires de Geneve, 1205 - Geneva/CH
  • 3 Department Of Oncology, Centre Léon Bérard, 69373 - Lyon/FR
  • 4 Infections And Cancer Epidemiology Group, International Agency for Research on Cancer, 69008 - Lyon/FR
  • 5 Departement Of Medical Oncology, Hospices Civils de Lyon, 69310 - Pierre-Bénite/FR
  • 6 Division Of Molecular Genetics, Hospices Civils de Lyon, 69310 - Pierre-Bénite/FR
  • 7 Unit Of Prevention And Genetic Epidemiology, Centre Leon Berard, 69008 - Lyon/FR
  • 8 Department Of Genetic Medicine, Hopitaux Universitaires de Geneve, 1205 - Geneva/CH
  • 9 Département D'oncologie Médicale, Centre Léon Bérard, 69008 - Lyon/FR
  • 10 Department Of Oncology, Hopitaux Universitaires de Geneve, 1211 - Geneva/CH
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Resources

Abstract 3393

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.

Clinical trial identification

Legal entity responsible for the study

Intidhar Labidi-Galy.

Funding

La Fondation Henriette Meyer.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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