The prognostic value of BRCA1 mRNA expression levels following neoadjuvant chemotherapy in breast cancer.
BACKGROUND
A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1 mRNA have longer survival following platinum-based chemotherapy than patients with high levels of BRCA1 mRNA.


RESULTS
Tumor biopsies were obtained from 86 breast cancer patients who were candidates for neoadjuvant chemotherapy, treated with four cycles of neoadjuvant fluorouracil, epirubicin and cyclophosphamide. Estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 and vimentin were examined by tissue microarray. HER2 were also assessed by chromogenic in situ hybridization, and BRCA1 mRNA was analyzed in a subset of 41 patients for whom sufficient tumor tissue was available by real-time quantitative PCR. Median time to progression was 42 months and overall survival was 55 months. In the multivariate analysis for time to progression and overall survival for 41 patients in whom BRCA1 could be assessed, low levels of BRCA1 mRNA, positive PR and negative lymph node involvement predicted a significantly lower risk of relapse, low levels of BRCA1 mRNA and positive PR were the only variables associated with significantly longer survival.


CONCLUSIONS
We provide evidence for a major role for BRCA1 mRNA expression as a marker of time to progression and overall survival in sporadic breast cancers treated with anthracycline-based chemotherapy. These findings can be useful for customizing chemotherapy.
Margeli
Mireia
M
Medical Oncology Service, Department of Medicine, Catalan Institute of Oncology, Hospital Germans Trias i Pujol and Autonomous University of Barcelona, Badalona, Spain. 33198mmv@comb.es
Cirauqui
Beatriz
B
Castella
Eva
E
Tapia
Gustavo
G
Costa
Carlota
C
Gimenez-Capitan
Ana
A
Barnadas
Agusti
A
Sanchez Ronco
Maria
M
Benlloch
Susana
S
Taron
Miquel
M
Rosell
Rafael
R
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008495:Medical Oncology / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger