Gender
Female
Age Group
18 Years to 65 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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:
- 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 endometrioid endometrial cancer
- Borderline or stage I ovarian cancer
- 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