Effect of Soy Supplementation on Cellular Markers in Normal and Cancerous Breast Tissue: A Randomized Placebo Controlled Study

Patient Population:

Pre and post menopausal women with breast cancer diagnosed by core needle biopsy scheduled
to undergo breast cancer resection for an invasive carcinoma.

Objectives:

- To determine (by immunohistochemistry) whether specific cellular markers and gene
products associated with breast carcinoma can be altered by soy therapy.

- To identify genes that can be altered by soy therapy in normal and neoplastic breast
tissues by unbiased gene expression analysis using microarrays.

- To compare specific cellular markers and pathways (immunohistochemistry), and gene
expression using microarrays in normal and cancerous breast tissue.

Study Design and Intervention Plan:

- Eligible patients will be consented at the time of visit with MSKCC breast surgeon and
randomized to receive soy (soy protein supplementation 50 grams/day), or placebo (milk
protein supplementation 50 grams/day) over the period until their surgery.

- The diagnostic biopsy (already available at time of appointment with MSKCC surgeon)
will be analyzed by immunohistochemistry for proliferation (Ki67) and apoptosis
(TUNEL). Additional immunohistochemistry will include HER2, TP53, cyclin D1, p27, BCL2,
ER and PR.

- Excision of the breast carcinoma (lumpectomy or mastectomy) will proceed in standard
fashion.

- The post-therapy excision specimen will be processed in a standard fashion. Pathologic
features, margin status, and tumor size will be assessed by a light microscopic
examination of histological sections. In addition to this routine processing,
immunohistochemistry assays for proliferation (Ki67), apoptosis (TUNEL), HER2, TP53,
cyclin D1, p27, BCL2, ER, and PR will be performed. For correlative biological studies
pathologists will select approximately .5 cubic mm representative sections of the
neoplastic tissues and normal adjacent breast tissue, which will be snap frozen for
gene expression analysis using microarrays.

Inclusion Criteria:

- Informed consent obtained

- Breast mass > .5 cm (determined by mammogram, ultrasound, MRI, or palpable criteria)

- Core biopsy diagnosis of invasive carcinoma of the breast

Exclusion Criteria:

- History of active malignancy within previous two years (except for non-melanoma skin
cancer and history of breast cancer).

- Regular soy consumption (consumption of more than 3 serving of soy or soy
products/supplements per week)

- Allergy to soy or milk protein