Effects of Short-Term Hormone Therapy before Surgery on Gene Profiles in Patients with Stage I-III Breast Cancer

PRIMARY OBJECTIVE:

I. To determine whether there is a reduction in the expression of proliferation marker Ki67, measured by immunohistochemistry (IHC) as well as single-gene read out, following short-term preoperative treatment with hormonal therapy.

SECONDARY OBJECTIVE:

I. To determine whether short term treatment results in significant reductions in the Mammaprint risk score, or in estrogen receptor (ER) or progesterone receptor (PR) expression as measured by IHC and single-gene read out.

EXPLORATORY OBJECTIVES:

I. Identify differentially expressed transcripts after short-term pre-operative, hormone treatment.

II. Identify transcripts for which gene expression is associate with measures of response, including changes in Ki67, ER and PR.

III. Perform full-transcriptome set analysis to identify pathway level changes associated with treatment.

IV. Comparison of expression changes between two standard of care molecular diagnostics: 70-GS and 21-GA.

OUTLINE: Patients are assigned to 1 of 3 groups.

GROUP I (PREMENOPAUSAL AND MEN): Patients receive tamoxifen orally (PO) daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

GROUP II (POSTMENOPAUSAL): Patients receive letrozole PO daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

GROUP III (POSTMENOPAUSAL): Patients receive exemestane PO daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.