for females ages 18-65 (full criteria)
at San Francisco, California and other locations
study started
completion around



RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer.

PURPOSE: This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer.

Official Title

A Phase III Trial Evaluating the Role of Ovarian Function Suppression and the Role of Exemestane as Adjuvant Therapies for Premenopausal Women With Endocrine Responsive Breast Cancer



  • Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with tamoxifen + ovarian function suppression (by triptorelin, oophorectomy, or ovarian irradiation) or exemestane + ovarian function suppression vs. tamoxifen alone. The primary comparison is ovarian function suppression with either tamoxifen or exemestane vs. tamoxifen alone.
  • Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, prior adjuvant/neoadjuvant chemotherapy (yes vs no), and number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more) and intended initial method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years.


Estrogen Receptor Positive Breast Cancer, Progesterone Receptor Positive Tumor, Recurrent Breast Carcinoma, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, tamoxifen, ovarian function suppression + tamoxifen, ovarian function suppression + exemestane, Breast Neoplasms, Triptorelin Pamoate, Exemestane, Tryptophan, Laboratory Biomarker Analysis, Oophorectomy, Quality-of-Life Assessment, Radiation Therapy, Triptorelin, T+OFS, E+OFS


You can join if…

Open to females ages 18-65

  • Premenopausal women (estradiol [E2] in the premenopausal range [according to institution parameters]) who meet the following criteria:
    • Patients who did not receive chemotherapy should be randomized within 12 weeks after definitive surgery; such patients should have estradiol (E2) in the premenopausal range following surgery; the only patients who do not require testing of estradiol (E2) to confirm premenopausal status are those who have been menstruating regularly during the 6 months prior to randomization and have not used any form of hormonal contraception or any other hormonal treatments during the 6 months prior to randomization
    • Patients who received prior adjuvant and/or neoadjuvant chemotherapy should be randomized after completing chemotherapy and within 8 months of the final dose of chemotherapy as soon as premenopausal status is confirmed; all such patients should have premenopausal status confirmed by an estradiol (E2) in the premenopausal range between 2 weeks and 8 months after completing chemotherapy
    • Adjuvant trastuzumab (Herceptin ®) is allowable, and is not considered to be chemotherapy for eligibility timing determination
    • Patients with temporary chemotherapy-induced amenorrhea who regain premenopausal status within eight months of the final dose of chemotherapy are eligible; (please note that some patients taking tamoxifen or aromatase inhibitors, even without evidence of menses, may have ovarian function recovery following chemotherapy and resume estradiol secretion); in patients wishing to participate in the study, with postmenopausal hormone levels shortly after chemotherapy, it is recommended to recheck their estradiol level at a later timepoint within 8 months of completing chemotherapy, even in the absence of return of menses
  • Histologically proven, resected breast cancer; pathology material should be available for submission for central review as part of the quality control measures for this protocol
  • Patients must have hormone receptor positive tumors; if there is more than one breast tumor, each tumor must be hormone receptor positive; hormone receptors must be determined using immunohistochemistry; estrogen receptor (ER) and/or progesterone receptor (PgR) must be greater than or equal to 10% of the tumor cells positive by immunohistochemical evaluation; biochemical determination alone is not acceptable
  • The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere, with the exception of tumor detected in internal mammary chain nodes by sentinel node procedure; patients who received neoadjuvant therapy must have had operable disease prior to neoadjuvant treatment to be eligible; patients who had a pathological evaluation with tru cut or core biopsy of invasive breast cancer prior to neoadjuvant therapy and were found to have no invasive tumor in the pathological specimen from definitive surgery are eligible; for these patients, pre-neoadjuvant tumor characteristics will be used for defining eligibility; in case of persistent disease, pathology findings from the definitive surgery should be used
  • Patients must have had proper surgery for primary breast cancer with no known clinical residual loco-regional disease:
    • A total mastectomy; radiotherapy is optional after mastectomy OR
    • A breast-conserving procedure (lumpectomy, quadrantectomy or partial mastectomy with margins clear of invasive cancer and ductal breast carcinoma in situ [DCIS]); the local pathologist must document negative margins of resection in the pathology report; 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 that all tumor has been removed; radiation therapy to the conserved breast is required; patients may be randomized before, during or after completion of radiation therapy to the breast
  • Either axillary lymph node dissection (pathological examination of at least 6 nodes recommended) or a negative axillary sentinel node biopsy (pN0[sn]) is required; patients with negative or microscopically axillary positive sentinel nodes (pN1mi: micrometastasis none > 2.0 mm) do not require further axillary therapy; those with positive sentinel nodes must have either an axillary dissection or radiation of axillary nodes
  • For International Breast Cancer Study Groups (IBCSG) centers, patients must have completed baseline Quality of Life (QL) Forms prior to randomization; the only exceptions are cognitive or physical impairment that interferes with QL assessment or inability to read any of the languages available on IBCSG QL forms; for non-IBCSG centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group
  • Written informed consent must be signed and dated by the patient and the investigator prior to randomization
  • Patients must be accessible for follow-up
  • Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines

You CAN'T join if...

  • 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
  • Patients with distant metastatic disease
  • 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
  • Patients with positive final margins (referring to only DCIS and invasive cancer, not lobular breast carcinoma in situ [LCIS]), except as noted; DCIS at a margin is permitted if a complete mastectomy has been performed
  • Patients with clinically detectable residual axillary disease
  • 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
  • Patients with previous or concomitant invasive malignancy are not eligible; the exceptions are patients with the following (and only the following) malignancies (previous or concomitant) who are eligible if adequately treated:
  • Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up; patients with previous thrombosis (e.g., deep vein thrombosis [DVT]) and/or embolism can be included only if medically suitable
  • Patients who have had a bilateral oophorectomy or ovarian irradiation; patients who will be recommended to undergo oophorectomy within 5 years (e.g., breast cancer susceptibility gene [BRCA]1/2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate
  • Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable
  • 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 five years including all types of hormonal contraception; a pregnancy test is recommended for women of child-bearing potential who are sexually active and not using reliable contraceptive methods
  • 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
  • Patients who were taking tamoxifen or other selective estrogen receptor modulator (SERM) (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis; prior oral contraceptives are allowed
  • Patients who have received GnRH analogues as part of their breast cancer treatment prior to randomization
  • Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements


  • San Francisco General Hospital
    San Francisco California 94110 United States
  • UCSF Medical Center-Mount Zion
    San Francisco California 94115 United States
  • California Pacific Medical Center-Pacific Campus
    San Francisco California 94115 United States
  • Kaiser Permanente-San Francisco
    San Francisco California 94115 United States
  • Kaiser Permanente-South San Francisco
    South San Francisco California 94080 United States
  • Bay Area Breast Surgeons Inc
    Emeryville California 94608 United States
  • Bay Area Tumor Institute
    Oakland California 94609 United States
  • Hematology and Oncology Associates-Oakland
    Oakland California 94609 United States
  • Tom K Lee Inc
    Oakland California 94609 United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley California 94704 United States


in progress, not accepting new patients
Start Date
Completion Date
ETOP IBCSG Partners Foundation
Phase 3 research study
Study Type
About 3066 people participating
Last Updated