| Exclusion Criteria: | 1) Patients who are postmenopausal (i.e., do not have an estradiol (E2) level in the premenopausal range) after surgery or after chemotherapy, whichever is later.
2) Patients with distant metastatic disease.
3) Patients with locally advanced inoperable breast cancer including inflammatory breast cancer or supraclavicular node involvement or with enlarged internal mammary nodes (unless pathologically negative) are not eligible. Patients with involved internal mammary nodes detected by sentinel node biopsy that are not enlarged are eligible.
4) Patients with positive final margins (referring to only DCIS and invasive cancer, not LCIS), except if all other margins are clear, a positive posterior (deep) margin is permitted provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents thall all tumor has been removed. DCIS at a margin is permitted if a complete mastectomy has been performed.
5) Patients with clinically detectable residual axillary disease.
6) Patients with a history of prior ipsilateral or contralateral invasive breast cancer. Patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible if the bilateral disease meets all other eligibility criteria.
7) Patients with previous or concomitant invasive malignancy EXCEPT adequately treated: basal or squamous cell carcinoma of the skin, in situ non breast carcinoma without invasion, contra-or ipsilateral in situ breast carcinoma, non-breast invasive malignancy diagnosed at least 5 years ago and without recurrence: ∙stage I papillary thyroid cancer, ∙stage Ia carcinoma of the cervix, ∙stage Ia or b endometroid endometrial cancer, ∙borderline or stage I ovarian cancer.
8) Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up. Patients with previous thrombosis (e.g, DVT) and/or embolism can be included only if medically suitable.
9) Patients who have had a bilateral oophorectomy or ovarian irradiation. Patients who will be recommended to undergo oophorectomy within 5 years (e.g., BRCA1 / 2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate.
10) Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable.
11) Patients who are pregnant or lactating at the time of randomization or who desire a pregnancy within 5 years. Patients planning to use additional hormonal therapy apart from the randomized treatment during the next 5 years including all types of hormonal contraception. A pregnancy test is required for women of child-bearing potential who are sexually active and not using reliable contraceptive methods.
12) Patients who received endocrine therapy (including neoadjuvant and adjuvant) for more than 8 months after their breast cancer diagnosis. Patients who are receiving endocrine therapy at randomization (and have received it for less than 8 months) may continue such therapy until protocol-specified tamoxifen/exemestane is initiated.
13) Patients who were taking tamoxifen or other SERM (e.g. Raloxifene) or hormone replacement (HRT) within one year prior to their breast cancer diagnosis. Prior oral contraceptives are allowed.
14) Patients who have received GnRH analogues as part of their breast cancer treatment prior to randomization.
15) Patients with psychiatric, addictive, or any disorder, that would prevent compliance with protocol requirements. |