Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study
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 cance...
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SMW supporting association (Trägerverein Swiss Medical Weekly SMW)
2023-03-01
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| Series: | Swiss Medical Weekly |
| Online Access: | https://smw.ch/index.php/smw/article/view/3307 |
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| author | Noémie Lang Aurélie Ayme Chang Ming Jean‑Damien Combes Victor N. Chappuis Alex Friedlaender Aurélie Vuilleumier José L. Sandoval Valeria Viassolo Pierre O. Chappuis S. Intidhar Labidi-Galy |
| author_facet | Noémie Lang Aurélie Ayme Chang Ming Jean‑Damien Combes Victor N. Chappuis Alex Friedlaender Aurélie Vuilleumier José L. Sandoval Valeria Viassolo Pierre O. Chappuis S. Intidhar Labidi-Galy |
| author_sort | Noémie Lang |
| collection | DOAJ |
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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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| format | Article |
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| institution | OA Journals |
| issn | 1424-3997 |
| language | English |
| publishDate | 2023-03-01 |
| publisher | SMW supporting association (Trägerverein Swiss Medical Weekly SMW) |
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| spelling | doaj-art-a8d8b33de2604ce9bbe07b894668f5ab2025-08-20T02:23:08ZengSMW supporting association (Trägerverein Swiss Medical Weekly SMW)Swiss Medical Weekly1424-39972023-03-01153310.57187/smw.2023.40055Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort studyNoémie LangAurélie AymeChang MingJean‑Damien CombesVictor N. ChappuisAlex FriedlaenderAurélie VuilleumierJosé L. SandovalValeria ViassoloPierre O. ChappuisS. Intidhar Labidi-Galy 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. https://smw.ch/index.php/smw/article/view/3307 |
| spellingShingle | Noémie Lang Aurélie Ayme Chang Ming Jean‑Damien Combes Victor N. Chappuis Alex Friedlaender Aurélie Vuilleumier José L. Sandoval Valeria Viassolo Pierre O. Chappuis S. Intidhar Labidi-Galy Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study Swiss Medical Weekly |
| title | Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study |
| title_full | Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study |
| title_fullStr | Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study |
| title_full_unstemmed | Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study |
| title_short | Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study |
| title_sort | chemotherapy related agranulocytosis as a predictive factor for germline brca1 pathogenic variants in breast cancer patients a retrospective cohort study |
| url | https://smw.ch/index.php/smw/article/view/3307 |
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