Suppression of Ovarian Function and Either Tamoxifen or Exemestane With or Without Chemotherapy in Treating Premenopausal Women With Resected Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: exemestane (Drug); tamoxifen citrate (Drug); triptorelin (Drug); adjuvant therapy (Procedure); chemotherapy (Procedure); oophorectomy (Procedure); radiation therapy (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: International Breast Cancer Study Group

Official(s) and/or principal investigator(s):
Rosalba Torrisi, MD, Study Chair, Affiliation: European Institute of Oncology
Rosalba Torrisi, MD, Study Chair, Affiliation: European Institute of Oncology

RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Suppression of ovarian function combined with hormone therapy may fight breast cancer by reducing the production of estrogen. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether suppression of ovarian function and hormone therapy are more effective with or without chemotherapy in treating breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving ovarian-function suppression together with hormone therapy and chemotherapy works compared to ovarian-function suppression and hormone therapy alone in treating premenopausal women with resected breast cancer.

Official title: A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women With Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy

Study design: Treatment, Randomized, Active Control

Primary outcome:

Relapse (i.e., local, regional, or distant)

Contralateral breast cancer

Second (nonbreast) primary tumor

Death

Secondary outcome: Overall survival

Detailed description: 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.

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). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive ovarian function suppression comprising triptorelin

intramuscularly on day 1 every 28 days for 5 years, oophorectomy, or ovarian irradiation. Beginning when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane once daily for 5 years in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive ovarian function suppression as in arm I and concurrent

chemotherapy for at least 2 months (if an anthracycline is included) or at least 4 months (if no anthracycline is included). Beginning after the completion of chemotherapy or when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane as in arm I.

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.

PROJECTED ACCRUAL: A total of 1,750 patients will be accrued for this study within 7 years.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

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

National Institute of Oncology, Budapest 1122, Hungary

Centro di Riferimento Oncologico - Aviano, Aviano 33081, Italy

European Institute of Oncology, Milan 20141, Italy

Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland

Kantonsspital - St. Gallen, St. Gallen CH-9007, Switzerland

Kantonsspital Graubuenden, Chur CH-7000, Switzerland

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information

Related publications:

Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.

Starting date: August 2003
Last updated: May 23, 2008