A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer

Inclusion Criteria:

- Histologically confirmed breast cancer

- Completely resected disease

- No clinically detectable residual loco-regional axillary disease

- Prior surgery for primary breast cancer of 1 of the following types:

- Total mastectomy with or without adjuvant radiotherapy

- Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial
mastectomy with margins negative* for invasive disease and ductal carcinoma
in situ) with planned radiotherapy

- Tumor confined to the breast and axillary nodes

- Tumor detected in internal mammary chain nodes by sentinel node procedure and is
not enlarged is allowed

- Axillary lymph node dissection or a negative axillary sentinel node biopsy required

- Patients with negative or microscopically positive axillary sentinel nodes are
eligible

- Positive sentinel nodes must have either axillary dissection or radiation of
axillary nodes

- No distant metastases

- No locally advanced inoperable breast cancer, including any of the following:

- Inflammatory breast cancer

- Supraclavicular node involvement

- Enlarged internal mammary nodes (unless pathologically negative)

- Bilateral synchronous invasive breast cancer allowed if disease meets all other
eligibility criteria

- No prior ipsilateral or contralateral invasive breast cancer

- Hormone receptor status:

- Estrogen and/or progesterone receptor positive

- At least 10% of the tumor cells positive by immunohistochemistry

- If > 1 breast tumor, each tumor must be hormone receptor positive

- Female

- Premenopausal

- Estradiol in the premenopausal range after prior surgery OR meets the following
criteria:

- Menstruating regularly for the past 6 months

- Has not used any form of hormonal treatment (including hormonal
contraception) within the past 6 months

- No systemic hepatic disease that would preclude prolonged follow-up

- No systemic renal disease that would preclude prolonged follow-up

- No systemic cardiovascular disease that would preclude prolonged follow-up

- No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is
medically suitable

- No systemic pulmonary disease that would preclude prolonged follow-up

- Not pregnant or nursing

- Fertile patients must use effective nonhormonal contraception

- No history of noncompliance to medical regimens

- No other nonmalignant systemic disease that would preclude prolonged follow-up

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, non-breast carcinoma in situ, contralateral or ipsilateral
carcinoma in situ of the breast, or other non recurrent invasive non-breast
malignancy, including any of the following:

- Stage I papillary thyroid cancer

- Stage IA carcinoma of the cervix

- Stage IA or B endometrioid endometrial cancer

- Borderline or stage I ovarian cancer

- No psychiatric, addictive, or other disorder that would preclude study compliance

- Prior or concurrent neoadjuvant or adjuvant trastuzumab allowed

- No prior neoadjuvant or adjuvant chemotherapy

- No prior tamoxifen, other selective estrogen-receptor modulators (SERMs) (e.g.,
raloxifene), or hormone replacement therapy for more than 1 year before breast cancer
diagnosis

- No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer

- No concurrent oral or transdermal hormonal therapy

- No other concurrent estrogen, progesterone, or androgens

- No other concurrent aromatase inhibitors

- No concurrent oral or other hormonal contraceptives (i.e., implants or depot
injections)

- No concurrent bisphosphonates, except in the following cases:

- Bone density is at least 1.5 standard deviations below the young adult normal
mean

- Participation in a randomized clinical study testing bisphosphonates in the
adjuvant breast cancer setting

- No prior ovarian radiotherapy

- No other concurrent investigational agents

- No prior bilateral oophorectomy