Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes.
BACKGROUND
Preclinical studies have indicated that BRCA1 functions differentially to modulate the chemosensitivity of cancer cells.


METHODS
To clarify these findings, BRCA1 expression in primary tumors was evaluated by immunohistochemistry in 50 patients with metastatic breast cancer.


RESULTS
BRCA1 expression was absent in 29 (58.0%) out of the 50 breast tumors tested. BRCA1-absent tumors were more frequently progesterone receptor-negative (p=0.019) than BRCA1-present tumors. Taxane-based chemotherapy was administered to 19 patients. Although BRCA1 expression did not relate to the clinical tumor response to taxane-based chemotherapy, time-to-progression (TTP) was significantly shorter in patients with BRCA1-absent tumors than in BRCA1-present tumors (mean+/-SD: 6.5 +/- 4.9 and 14.7 +/- 5.9 months, respectively; p=0.006). The Cox proportional hazard model revealed that BRCA1 absence was an independent predictor of progression (hazard ratio: 3.22; p=0.035).


CONCLUSIONS
These results suggest that the absence of BRCA1 expression is an independent predictor of shorter TTP in advanced breast cancer patients treated with taxane-based chemotherapy.
Kurebayashi
Junichi
J
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, Japan. kure@med.kawasaki-m.ac.jp
Yamamoto
Yutaka
Y
Kurosumi
Masafumi
M
Okubo
Sumiko
S
Nomura
Tsunehisa
T
Tanaka
Katsuhiro
K
Sonoo
Hiroshi
H
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000172:deficiency; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D000077268:Pamidronate; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019313:BRCA1 Protein; D004164:Diphosphonates; D043823:Taxoids; D000077143:Docetaxel; D017258:Medroxyprogesterone Acetate; D000077268:Pamidronate; D000068878:Trastuzumab; D017239:Paclitaxel