The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients.
OBJECTIVE
The presence of BRCA gene mutation and low expressions of BRCA proteins are associated with a greater sensitivity of tumor cells to ionizing radiation and to cytostatics damaging the DNA of the cells. The purpose of this study was to estimate the rate of adverse events in BRCA1/2-associated breast cancer patients receiving anthracycline-based chemotherapy compared to patients without mutation. The authors also compared radiotherapy toxicity in these 2 groups.


METHODS
The analysis included 270 early-stage breast cancer patients treated between 2006 and 2012. All patients were examined for the presence of BRCA1/2 mutations.


RESULTS
BRCA mutation was detected in 41 (15%) patients. Toxicity grade 3, especially nausea and vomiting, was observed more often in noncarriers (7 vs. 13%, p = 0.0008). Neutropenia was detected more frequently in patients with BRCA1/2 mutation (32 vs. 10%), but only after 1 cycle of chemotherapy (p = 0.0007). There was increased radiation toxicity in BRCA1/2 patients who underwent mastectomy and neoadjuvant chemotherapy (p = 0.016).


CONCLUSIONS
BRCA1/2 mutation carriers seemed to be more at risk of neutropenia after the first cycle of the treatment. In terms of other side effects, there was a lack of increased toxicity in this group. Mastectomy and neoadjuvant chemotherapy were risk factors for radiation toxicity in mutation carriers.
Clinical and Experimental Oncology Department, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Joanna
J
Huszno
Magdalena
M
Budryk
Zofia
Z
Kołosza
Elżbieta
E
Nowara
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D005260:Female; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009154:Mutation; D009325:Nausea / Q000139:chemically induced; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods; D009503:Neutropenia / Q000139:chemically induced; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D012189:Retrospective Studies; D012867:Skin / Q000528:radiation effects; D014839:Vomiting / Q000139:chemically induced
D018943:Anthracyclines; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human