Radiation Therapy in Treating Women With Early Stage Breast Cancer

Safety and Feasibility of Accelerated, Hypofractionated Radiotherapy in Women With Breast Cancer: A Phase II Trial

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in different ways may kill more tumor cells. Giving it after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects of radiation therapy and to see how well it works in treating women with early stage breast cancer.

OBJECTIVES:

Primary

• To determine the freedom from local and regional failure in women with early stage breast cancer treated with accelerated, hypofractionated radiotherapy.
• To determine the acute and late toxicity of accelerated, hypofractionated radiotherapy using previously published toxicity scales.

Secondary

• To measure cosmesis using the Harvard cosmesis scale in patients who have undergone lumpectomy.
• To identify co-variates responsible for poor cosmetic outcome in these patients.

OUTLINE: Patients who have undergone lumpectomy undergo either intracavitary balloon brachytherapy boost and hypofractionated, accelerated whole breast irradiation (AWBI) OR 3D-conformal radiotherapy (3D-CRT)/intensity-modulated radiotherapy (IMRT) boost and AWBI. Patients who have undergone mastectomy undergo hypofractionated, accelerated chest wall irradiation.

• Intracavitary balloon brachytherapy boost and AWBI (post-lumpectomy): Patients undergo intracavitary balloon brachytherapy boost twice daily for 2 days (total of 4 fractions). Beginning 5-21 days after completion of brachytherapy, patients undergo AWBI once daily 5 days a week for approximately 2 weeks (total of 11 fractions).
• 3D-CRT/IMRT boost and AWBI (post-lumpectomy): Patients undergo 3D-CRT/IMRT boost twice daily for 2 days (total of 4 fractions). Patients also undergo AWBI as above before or after boost radiotherapy.
• Accelerated chest wall irradiation (post-mastectomy): Patients undergo accelerated chest wall irradiation once daily 5 days a week for approximately 2 weeks (total of 11 fractions).

Patients who have undergone lumpectomy undergo frontal digital photography of the breasts at baseline, immediately before the initiation of radiotherapy, and then annually for 3 years after completion of radiotherapy. These patients also complete the Breast Cancer Treatment Outcome Scale at baseline and at 3 years after completion of radiotherapy. Physicians complete the Harvard Cosmesis scale at baseline and at 1 and 3 years after completion of radiotherapy.

After completion of study treatment, patients are followed up at weeks 1, 4, and 8 and then every 4 months for 2 years, every 6 months for 3 years, and annually thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer, including 1 of the following subtypes:

  • Ductal carcinoma in situ
  • Invasive ductal carcinoma
  • Invasive lobular carcinoma
  • Medullary carcinoma
  • Papillary carcinoma
  • Colloidal (mucinous) carcinoma
  • Tubular carcinoma

• Pathological stage 0-IIIA disease (pTis; pT1-2, N0-N2a, M0)

  • Tumor size ≤ 5 cm

• Breast considered technically satisfactory for radiotherapy

• Has undergone lumpectomy or mastectomy and either sentinel node biopsy or axillary dissection (if invasive carcinoma is present)

  • Negative inked histological margins (i.e., no invasive cells at surgical margin) or confirmed negative re-excision specimen

• Unifocal or multifocal (confined to 1 quadrant; tumors < 4 cm apart) disease with 1 or 2 foci that can be encompassed by 1 lumpectomy

• No proven multicentric carcinoma (tumors in different quadrants of the breast or tumor separated by ≥ 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy

• No evidence of suspicious microcalcifications in the breast before the start of radiotherapy

  • If malignancy-associated microcalcifications were initially present, the post-excision mammography must be negative

• No more than 9 positive axillary lymph nodes

• No palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor

• No previously treated contralateral breast cancer or synchronous ipsilateral breast cancer

• No lobular carcinoma in situ alone (i.e., no invasive component) or non-epithelial breast malignancies (e.g., sarcoma or lymphoma)

• No Paget disease of the nipple

• No skin involvement, regardless of tumor size

• No distant metastases

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Pre- or post-menopausal
• ECOG performance status 0-1
• No co-existing medical condition that would limit life expectancy to < 2 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except for nonmelanoma skin cancer (the disease-free interval from any prior malignancy must be continuous)
• No collagen vascular disease, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis
• No psychiatric or addictive disorder that would preclude obtaining informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiotherapy for the current breast cancer

• No tylectomies so extensive that the cosmetic result is low or poor prior to radiotherapy

• Chemotherapy allowed provided the following criteria are met:

  • Chemotherapy is not administered prior to, during, and for ≥ 21 days after completion of radiotherapy (for patients receiving brachytherapy boost)
  • Chemotherapy is not administered for ≥ 21 days before, during, and for ≥ 21 days after completion of radiotherapy (for patients receiving external beam radiotherapy boost or chest wall irradiation)

• Concurrent tamoxifen, anastrozole, or other hormonal therapy allowed

  • May be initiated before, during, or after radiotherapy

• No other concurrent chemotherapy, immunotherapy, or experimental medications