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Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study. | LitMetric

AI Article Synopsis

  • Patients with germline BRCA1 pathogenic variants tend to experience higher rates of agranulocytosis (a serious drop in white blood cell count) after the first cycle of chemotherapy, suggesting a link between the gene variant and chemotherapy toxicity.
  • In a study of 307 non-metastatic breast cancer patients who underwent genetic counseling, those with gBRCA1 variants showed higher occurrences of grade 3 disease, triple-negative breast cancer, and agranulocytosis.
  • The presence of agranulocytosis was found to significantly increase the predictive accuracy of identifying gBRCA1 variants, with odds favoring its use as a predictive factor in clinical settings.

Article Abstract

Background: Carriers of germline pathogenic variants of the BRCA1 gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predict gBRCA1 pathogenic variants.

Patients And Methods: The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouring gBRCA1 pathogenic variants among patients presenting agranulocytosis during C1.

Results: Three hundred seven BC patients were included: 32 (10.4%) gBRCA1, 27 (8.8%) gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes, gBRCA1 heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive for gBRCA1 pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predicting gBRCA1 were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used for gBRCA1 evaluation.

Conclusion: Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1 detection in non-metastatic BC patients.

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Source
http://dx.doi.org/10.57187/smw.2023.40055DOI Listing

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