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