Adjuvant Chemotherapy in Treating Women Who Have Undergone Resection for Relapsed Breast Cancer; Chemotherapy as Adjuvant for LOcally Recurrent Breast Cancer

OBJECTIVES:

Primary

• Determine the efficacy of adjuvant chemotherapy, in terms of disease-free survival, in women with radically resected loco-regional relapsed breast cancer.

Secondary

• Determine the systemic disease-free and overall survival of patients treated with this regimen.
• Determine the sites of recurrence, incidence of second (non-breast) malignancies, and causes of death without relapse of breast cancer in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen (QOL portion closed 11/13/08).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior chemotherapy (yes vs no), estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (yes vs no), and location of recurrence (breast vs mastectomy scar/chest wall vs regional lymph nodes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive radiotherapy* within 6 months after surgery.
• Arm II: Within 10 weeks after surgery, patients receive at least 3 courses of an adjuvant chemotherapy regimen as determined by the investigator. Patients also receive radiotherapy* within 6 months after surgery and after the completion of chemotherapy OR integrated with chemotherapy.

NOTE: *Patients with clear margins (R0) who received prior adjuvant radiotherapy are not required to receive further radiotherapy

Patients with ER and/or PR positive tumors also receive standard hormonal therapy.

Quality of life is assessed at baseline and at 9 and 12 months (QOL portion closed 11/13/08).

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 265 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer

• First local and/or regional (i.e., ipsilateral axillary or internal mammary lymph node region) recurrence after primary treatment with mastectomy or lumpectomy/quadrantectomy with clear surgical margins

• Local failure is defined as a tumor recurrence in any soft tissue of the ipsilateral conserved breast or the chest wall, mastectomy scar, and/or skin
• Regional failure is defined as a tumor recurrence in the ipsilateral axillary lymph nodes, extranodal soft tissue of the ipsilateral axilla, and/or ipsilateral internal mammary. Regional failure does not include supraclavicular lymph nodes or tumor in the opposite breast
• No other prior recurrence in any site, including local
• Surgical resection of the recurrence meeting 1 of the following criteria:

• Uninvolved ("clear") margins and planned radiotherapy with at least 40 Gy for patients who had no prior adjuvant radiotherapy
• Mastectomy of the recurrence with uninvolved ("clear") margins after lumpectomy/quadrantectomy alone for the primary
• Adjuvant trastuzumab (Herceptin®) therapy or other HER-2 directed therapies are allowed for patients with HER-2 positive tumors and must be declared prior to randomization
• No evidence of distant metastasis, including ipsilateral supraclavicular lymph nodes, by x-ray or CT scan of the chest, ultrasound or CT scan of the abdomen and pelvis, or bone scintigraphy only if alkaline phosphatase is > 2 times normal or if medically indicated (e.g., bone pain)
• No macroscopically incomplete surgery
• No bilateral malignancy except carcinoma in situ
• No suspicious mass in the opposite breast unless that mass has been proven by biopsy to be benign
• No skeletal pain of unknown cause

• No hot spots on bone scan for which metastases cannot be ruled out by x-ray, MRI, and/or CT scan
• Hormone receptor status:

• Determined in the recurrent tumor by immunohistochemistry and/or ligand-binding assay
• Estrogen receptor positive or negative
• Progesterone receptor positive or negative

PATIENT CHARACTERISTICS:

Age

• Minimum 18 years

Sex

• Female

Menopausal status

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No elevated alkaline phosphatase

Renal

• Not specified

Other

• Fertile patients must use effective non-hormonal contraception
• Medically suitable for chemotherapy of 3-6 months duration
• No other primary malignant tumors except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• No non-malignant systemic disease that would preclude study treatment or prolong follow-up
• No psychiatric or addictive disorder that would preclude giving informed consent
• No history of noncompliance to medical regimens or potential for being unreliable

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics