Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer.
OBJECTIVE
Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment. We studied 282 patients participating in a randomized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry.


METHODS
Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used.


RESULTS
HER-2/neu overexpression was a negative prognostic factor for overall survival. In univariate analyses, in HER-2/neu-positive patients, the hazard ratio (HR) for disease-free survival (DFS) with adjuvant endocrine therapy was 0.37 (95% confidence interval [CI], 0.26 to 0.89); for HER-2/neu-negative patients, the corresponding HR for DFS was 0.48 (95% CI, 0.31 to 0.71). The overall survival (OS) data were HR=0.26 (95% CI, 0.07 to 0.92) and HR=0.68 (95% CI, 0.32 to 1.42) for HER-2/neu-positive and HER-2/neu-negative patients, respectively. In multivariate models, the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS, respectively. Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment.


CONCLUSIONS
HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor-positive tumors.
Love
Richard R
RR
Departments of Medicine and Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53726, USA. rrlove@facstaff.wisc.edu
Duc
Nguyen Ba
NB
Havighurst
Thomas C
TC
Mohsin
Syed K
SK
Zhang
Qian
Q
DeMets
David L
DL
Allred
D Craig
DC
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010052:Ovariectomy; D017697:Premenopause; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen