High p27Kip1 expression predicts superior relapse-free and overall survival for premenopausal women with early-stage breast cancer receiving adjuvant treatment with tamoxifen plus goserelin.
OBJECTIVE
To determine the predictive value of p27Kip1 in premenopausal women with early-stage hormone receptor-positive breast cancer.


METHODS
We retrospectively examined tumor specimens from 512 patients with breast cancer who were enrolled onto Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5. In this trial, premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease were randomly assigned to receive either 5 years of tamoxifen plus 3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil. p27Kip1 expression was assessed by immunohistochemistry, and its association with clinical outcome was determined. Statistical analyses were performed to test for interaction between p27Kip1 status and treatment.


RESULTS
High p27Kip1 expression (nuclear p27Kip1 staining in >/= 50% of tumor cells) independently predicted superior relapse-free survival (RFS) and overall survival (OS) in both the total study population (RFS: relative risk [RR], 0.53; 95% CI, 0.34 to 0.82; P =.004; OS: RR, 0.29; 95% CI, 0.15 to 0.58; P <.001) and patients treated with combination endocrine therapy (RFS: RR, 0.32; 95% CI, 0.16 to 0.63; P =.001; OS: RR, 0.16; 95% CI, 0.05 to 0.53; P =.003). The interaction between p27Kip1 expression and treatment was statistically significant for RFS (P =.04) but not for OS (P =.27).


CONCLUSIONS
High p27Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor-positive breast cancer for adjuvant combination endocrine therapy.
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018931:Antineoplastic Agents, Hormonal; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D017273:Goserelin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases