Radiation Therapy (WBI Versus PBI) in Treating Women Who Have Undergone Surgery For Ductal Carcinoma In Situ or Stage I or Stage II Breast Cancer

OBJECTIVES:

Primary

- Compare local tumor control in women with ductal carcinoma in situ or stage I or II
breast cancer treated with adjuvant whole breast vs partial breast irradiation following
lumpectomy.

Secondary

- Compare overall survival, recurrence-free survival, and distant disease-free survival in
patients treated with these regimens.

- Compare the cosmetic result in patients treated with these regimens.

- Compare fatigue and treatment-related symptoms in patients treated with these regimens.

- Compare perceived convenience of care in patients treated with these regimens.

- Compare acute and late toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
disease stage (ductal carcinoma in situ [DCIS] only vs invasive and node negative vs invasive
with 1-3 positive nodes), menopausal status (premenopausal vs postmenopausal), hormone
receptor status (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive
vs ER-negative and PR-negative), intention to receive chemotherapy (yes vs no). Patients are
randomized to 1 of 2 treatment arms. (Patients who are 50 years of age and over with DCIS
regardless of hormone receptor status AND patients with invasive breast cancer meeting all of
the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive
status will not be enrolled in study after 12/30/2006.)

- Group 1: Patients undergo whole-breast irradiation (WBI) once daily, 5 days a week, for
5-7 weeks.

- Group 2: Patients undergo partial-breast irradiation (PBI) twice daily on 5 days over a
period of 5-10 days. This may be delivered by multi-catheter brachytherapy, single-entry
intracavitary brachytherapy, or 3-D conformal radiotherapy.

Patients in both arms may receive adjuvant chemotherapy at least 2 weeks prior to initiation
of WBI OR at least 2 weeks after completion of PBI at the discretion of the treating
physician. Patients with ER-positive or PR-positive tumors may also receive hormonal therapy,
beginning 3-12 weeks after completion of adjuvant chemotherapy (or before, during, or after
completion of WBI or PBI for patients not receiving adjuvant chemotherapy) and continuing for
at least 5 years.

After completion of study treatment, patients are followed at 1 and 6 months, every 6 months
for 4.5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,300 patients (2,150 per treatment arm) will be accrued for
this study within 4.6 years. Note: Accrual closed on April 16, 2013, following approval of
the Data Monitoring Committee to reduce the sample size from 4,300 to 4,214 patients.

DISEASE CHARACTERISTICS:

- Histologically confirmed ductal carcinoma in situ (DCIS*) or invasive* adenocarcinoma
of the breast

- Stage 0, I, or II disease

- Stage II tumors must be ≤ 3 cm

- Gross disease must be unifocal

- Microscopic multifocality allowed provided total pathological tumor size is
≤ 3 cm

- No proven multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm

- No non-epithelial breast malignancies (e.g., sarcoma or lymphoma) NOTE: *Patients
who are 50 years of age and over with DCIS regardless of hormone receptor status
AND patients with invasive breast cancer meeting all of the following criteria: ≥
50 years of age, node-negative, and hormone-receptor positive status will not be
enrolled in study after 12/30/2006

- Prior axillary staging required for patients with invasive breast cancer, including 1
of the following:

- Sentinel node biopsy alone (if sentinel node is negative)

- Sentinel node biopsy followed by axillary dissection or sampling with ≥ 6
axillary nodes (if sentinel node is positive)

- Axillary dissection alone with ≥ 6 axillary nodes

- No more than 3 positive axillary nodes

- No axillary nodes with definite evidence of microscopic or macroscopic
extracapsular extension

- No positive non-axillary sentinel nodes (intramammary nodes are staged as
axillary nodes)

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

- Must have undergone lumpectomy

- Resected margins histologically free of tumor

- Re-excision of surgical margins allowed

- Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast
reference volume ≤ 30% based on postoperative pre-randomization CT scan

- Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging
procedure) within the past 42 days

- No suspicious microcalcifications, densities, or palpable abnormalities in the
ipsilateral or contralateral breast unless biopsied and found to be benign

- No Paget's disease of the nipple

- No history of invasive breast cancer or DCIS

- Prior lobular carcinoma in situ treated by surgery alone allowed

- No synchronous bilateral invasive or non-invasive breast cancer

- Partial breast irradiation deemed technically deliverable by radiation oncologist at a
credentialed facility

- Must have undergone a history and physical exam within the past 4 months AND a
bilateral mammogram within the past 6 months

- Hormone receptor status:

- Estrogen receptor (ER) status known

- Progesterone status known if ER analysis is negative

- Marginal or borderline results are considered positive

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Premenopausal or postmenopausal

Performance status

- Not specified

Life expectancy

- At least 10 years, excluding diagnosis of breast cancer

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Not specified

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception

- No other malignancy within the past 5 years except previously treated carcinoma in
situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell skin
cancer

- Deemed to be at low risk for recurrence

- No collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma),
specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal,
or active skin rash

- No psychiatric or addictive disorder that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic therapy for this malignancy

Chemotherapy

- No prior chemotherapy for this malignancy

- No concurrent chemotherapy during study radiotherapy

Endocrine therapy

- No prior hormonal therapy for this malignancy unless total duration of hormonal
therapy was no more than 28 days before randomization

- Concurrent hormonal therapy allowed provided it is not administered during
chemotherapy

- No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating
drugs

- No concurrent hormone replacement therapy

- No concurrent Femring^®

Radiotherapy

- No prior radiotherapy for this malignancy

- No prior breast or thoracic radiotherapy

- No concurrent brachytherapy boosts

- No concurrent intensity modulated radiotherapy

- No concurrent regional nodal irradiation

Surgery

- See Disease Characteristics

- No prior breast implants

- Patients who have had implants removed are eligible

Other

- No other concurrent anticancer therapy