title: Toxicity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2-associated breast cancer.
abstract: Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells with only one normal copy of either the BRCA1 or BRCA2 gene is sufficiently functional to handle acute chemotherapy-associated toxicity.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands. j.drooger@ikazia.nl.|Department of Medical Oncology, Ikazia Hospital, Rotterdam, The Netherlands. j.drooger@ikazia.nl.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Drooger
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands.
authors.forename: Bernadette A M
authors.initials: BAM
authors.lastname: Heemskerk-Gerritsen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands.
authors.forename: Nyrée
authors.initials: N
authors.lastname: Smallenbroek
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands.|Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Epskamp
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Seynaeve
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, PO Box 5201, 3008, AE, Rotterdam, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D043823:Taxoids
keywords: BRCA mutation; Breast cancer; Chemotherapy; Dose intensity; Toxicity