Premenopausal Endocrine Responsive Chemotherapy Trial
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: chemotherapy; exemestane; tamoxifen; triptorelin; oophorectomy; ovarian irradiation
Intervention description: Planned duration of chemotherapy: 2 months if an anthracycline is included (e.g., 4 cycles of EC or AC) or 4 months if no anthracycline is given (e.g., 6 cycles of CMF) is recommended. Unless medically contraindicated, an anthracycline-containing regimen using epirubicin should be given.; Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.; Triptorelin (GnRH analogue) 3.75 mg by intramuscular injection every 28 days for 5 years from randomization, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.; Bilateral surgical oophorectomy via laparotomy or laparoscopy.; Bilateral ovarian irradiation.
Intervention MeSH terms: Tamoxifen; Epirubicin; Exemestane; Triptorelin Pamoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Female
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: stage IIIA breast cancer; stage I breast cancer; stage II breast cancer

Summary:

      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.
    

Eligibility 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