Premenopausal Endocrine Responsive Chemotherapy Trial
Premenopausal Endocrine Responsive Chemotherapy Trial
The PERCHE trial evaluated the worth of adding adjuvant chemotherapy for premenopausal women
 with steroid hormone receptor positive early invasive breast cancer who receive ovarian
 function suppression plus either tamoxifen or exemestane for five years. The use of
 chemotherapy was determined by randomization. The method of ovarian function suppression
 (GnRH analogue for five years, surgical oophorectomy or ovarian irradiation) and the choice
 of tamoxifen or exemestane were determined by the investigator or by randomization in the
 IBCSG 25-02 TEXT trial [recommended option]. The trial was terminated early due to poor
 accrual.
OBJECTIVES:

 -  Compare ovarian function suppression and tamoxifen or exemestane with vs without
 adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast
 cancer.

 -  Compare the disease-free and overall survival of patients treated with these regimens.

 -  Compare sites of first treatment failure in patients treated with these regimens.

 -  Compare the incidence of second nonbreast malignancies in patients treated with these
 regimens.

 -  Compare the quality of life, including late side effects of early menopause, of patients
 treated with these regimens.

 PLANNED OUTLINE:

 This is a randomized, multicenter study. Patients are stratified according to participating
 center, number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more),
 method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation),
 chemotherapy if randomized to arm II (not containing vs containing an anthracycline or
 taxane), and endocrine agent (tamoxifen vs exemestane vs selected by subsequent randomization
 in the TEXT trial). Treatment duration is five years.

 Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4
 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then
 annually thereafter.

 NOTE: Trial was terminated early due to poor accrual.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed breast cancer confined to the breast and axillary nodes

 -  No distant metastatic disease

 -  Tumor detected in the internal mammary chain by sentinel node procedure allowed

 -  Must have undergone 1 of the following procedures for primary breast cancer within the
 past 12 weeks and have no known clinical residual locoregional disease:

 -  Total mastectomy with or without adjuvant radiotherapy

 -  Breast-conserving surgery (e.g., lumpectomy, quadrantectomy, or partial
 mastectomy with margins clear* of invasive cancer and ductal carcinoma in situ)
 followed by radiotherapy NOTE: *If all other margins are clear, a positive
 posterior (deep) margin is permitted, provided the excision was performed down to
 the pectoral fascia and all tumor has been removed OR a positive anterior
 (superficial; abutting skin) margin is allowed provided all tumor was removed

 -  Prior axillary lymph node dissection or negative axillary sentinel node biopsy
 required

 -  Patients with microscopically positive axillary sentinel nodes allowed provided
 they were evaluated on a clinical trial evaluating microscopically positive lymph
 nodes

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

 -  Inflammatory breast cancer

 -  Supraclavicular node involvement

 -  Enlarged internal mammary nodes (unless pathologically negative)

 -  No prior ipsilateral or contralateral invasive breast cancer

 -  Histologically diagnosed synchronous bilateral invasive breast cancer within the
 past 2 months allowed if the bilateral disease meets all other eligibility
 criteria

 -  Hormone receptor status:

 -  Estrogen receptor and/or progesterone receptor positive in each tumor

 -  At least 10% of tumor cells positive by immunohistochemistry

 PATIENT CHARACTERISTICS:

 Age

 -  Premenopausal

 Sex

 -  Female

 Menopausal status

 -  Premenopausal

 -  Estradiol in the premenopausal range after surgery

 Performance status

 -  Not specified

 Life expectancy

 -  Not specified

 Hematopoietic

 -  Not specified

 Hepatic

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

 Renal

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

 Cardiovascular

 -  No prior deep venous thrombosis and/or embolism unless patient is medically suitable

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

 Pulmonary

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

 Other

 -  Not pregnant or nursing

 -  Fertile patients must use effective nonhormonal contraception

 -  No other prior or concurrent invasive malignancy except adequately treated basal cell
 or squamous cell skin cancer, nonbreast carcinoma in situ without invasion,
 contralateral or ipsilateral carcinoma in situ of the breast

 -  No prior or concurrent nonbreast invasive malignancy within the past 5 years that is
 nonrecurrent 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 other nonmalignant systemic disease that would preclude prolonged follow-up

 -  No history of noncompliance with medical regimens

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

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  Not specified

 Chemotherapy

 -  No prior neoadjuvant or adjuvant chemotherapy

 -  Neoadjuvant or adjuvant trastuzumab (Herceptin®) allowed

 Endocrine therapy

 -  No prior neoadjuvant or adjuvant endocrine therapy after breast cancer diagnosis

 -  No prior tamoxifen or other selective estrogen-receptor modulator (e.g., raloxifene)
 within 1 year before the breast cancer diagnosis

 -  No other concurrent oral or transdermal hormonal therapy, including any of the
 following:

 -  Estrogen

 -  Progesterone

 -  Androgens

 -  Aromatase inhibitors

 -  Hormone replacement therapy

 -  Oral or other hormonal contraceptives, including implant and depot injections

 -  Raloxifene or other selective estrogen-receptor modulators

 Radiotherapy

 -  See Disease Characteristics

 -  No prior ovarian irradiation

 Surgery

 -  See Disease Characteristics

 -  No prior bilateral oophorectomy

 Other

 -  No other prior neoadjuvant therapy

 -  No other concurrent investigational agents

 -  No concurrent bisphosphonates unless bone density has been documented at least 1.5
 standard deviations below the young adult normal mean or the patient is participating
 in a randomized clinical trial setting testing bisphosphonates in the adjuvant breast
 cancer setting