Hypofractionated Regional Nodal Irradiation Clinical Trial for Women With Breast Cancer

Inclusion Criteria:

• Karnofsky performance status of 70-100%

• Histologic documentation of invasive adenocarcinoma of the breast

• One of the breast disease stages listed below:

• Note: In the definitions below, definitive surgery is defined as the finalsurgery performed to obtain clear surgical margins

• Neoadjuvant chemotherapy was not administered ** If neoadjuvant chemotherapywas NOT administered, pathologic staging must be T1-3, N1-2a followingdefinitive surgery

• Neoadjuvant chemotherapy was administered

• If prior to initiation of neoadjuvant chemotherapy clinical staging wasT1-3, N0, pathologic staging must be T1-3, N1-2a following definitivesurgery

• If prior to initiation of neoadjuvant chemotherapy clinical staging wasT1-3, N1, pathologic staging must be T0-3, N0-2a following definitivesurgery

• If prior to initiation of neoadjuvant chemotherapy there was cytologic orpathologic confirmation of axillary nodal involvement (per any of thecriteria listed below), pathologic staging must be T0-3, N0-2a followingdefinitive surgery

• Positive fine-needle aspiration (FNA) (ie, demonstrating malignantcells)

• Positive core needle biopsy (ie, demonstrating invasiveadenocarcinoma)

• Positive sentinel lymph node biopsy (ie, demonstrating invasiveadenocarcinoma)

• Complete resection of known breast disease by one of the following surgeries:

• Lumpectomy with sentinel lymph node or axillary lymph node dissection

• Mastectomy alone with sentinel lymph node or axillary lymph node dissection

• Mastectomy plus reconstruction with sentinel lymph node or axillary lymph nodedissection

• Margins of the resected specimen or re-excision specimen must be histologically freeof invasive tumor and ductal carcinoma in situ (DCIS) as determined by thepathologist

• Notes: Additional operative procedures may be performed to obtain clear margins;focally positive margins are acceptable based on technical feasibility of additionalsurgery and/or the potential for benefit with further surgery based on the extentand location of the positive margin (eg, focally positive deep margin at thepectoralis fascia); also, patients with margins positive for lobular carcinoma insitu (LCIS) are eligible without additional resection

• Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growthfactor receptor 2 (HER2) testing performed on the primary breast tumor; whenapplicable, testing must have been performed prior to neoadjuvant chemotherapy

• Interval between the last surgery for breast cancer (including re-excision ofmargins) or the completion of adjuvant chemotherapy and study enrollment must be =< 56 days (ie, a maximum of 8 weeks)

• Note: Radiotherapy must begin within 10 weeks following the last surgery forbreast cancer or the last dose of adjuvant chemotherapy

• Recovery from surgery with the incision completely healed and no signs of infection

• If adjuvant chemotherapy was administered, chemotherapy-related toxicity that mayinterfere with delivery of external beam radiation therapy (EBRT) should haveresolved

• Women who are not postmenopausal or have not undergone hysterectomy must have adocumented negative pregnancy test within 14 days prior to study registration

• Note: Postmenopausal is defined as one or more of the following:

• Age >= 60 years

• Age < 60 years and amenorrheic for at least 1 year with follicle-stimulatinghormone (FSH) and plasma estradiol levels in the postmenopausal range

• Bilateral oophorectomy

• Women of child-bearing potential (WCBP) must agree to use a medically accepted formof pregnancy prevention for the duration of study treatment

• Ability to understand and willingness to sign the consent form written in Englishpregnancy test within 14 days prior to study registration

• Note: Postmenopausal is defined as one or more of the following:

• Age >= 60 years

• Age < 60 years and amenorrheic for at least 1 year with follicle-stimulatinghormone (FSH) and plasma estradiol levels in the postmenopausal range

• Bilateral oophorectomy

• Women of child-bearing potential (WCBP) must agree to use a medically accepted formof pregnancy prevention for the duration of study treatment

• Ability to understand and willingness to sign the consent form written in English

Exclusion Criteria:

• Known definitive clinical or radiologic evidence of metastatic disease

• T4 tumors including inflammatory breast cancer

• Clinical nodal staging of N2 or N3 disease

• Pathologic nodal staging of N2b, N2c, or N3 disease

• Microscopic positive margins after definitive surgery

• Note: Patients with microscopically focally positive margins following lumpectomyor mastectomy are not excluded if re-excision is not technically feasible and/orthere is no benefit to further surgery based on the extent and location of thepositive margin

• Any history, not including the index cancer, of ipsilateral or contralateralinvasive breast cancer or ipsilateral or contralateral DCIS treated with radiationtherapy (RT)

• Note: Patients with synchronous or previous ipsilateral LCIS are eligible

• Any radiation therapy (RT) for the currently diagnosed breast cancer prior to studyenrollment

• History of ipsilateral or contralateral breast or thoracic RT for any condition

• History of ipsilateral or contralateral axillary surgery for any condition

• History of lymphedema involving the ipsilateral or contralateral arm at present orat any time in the past

• Synchronous contralateral breast cancer requiring RT

• Overall geometry (eg, breast size if intact breast) precludes the ability to achievedosimetric requirements

• Note: Set-up devices for breast positioning are permitted

• Unresolved post-surgical complications (eg, significant infection) with healingdifficulties

• Active collagen vascular disease, specifically dermatomyositis with a creatinephosphokinase (CPK) level above normal or with an active skin rash, systemic lupuserythematosus, or scleroderma

• Pregnancy or breastfeeding

• Diagnosis or treatment for a non-breast malignancy within 5 years of studyregistration, with the following exceptions: complete resection of basal cellcarcinoma or squamous cell carcinoma of the skin and any in situ malignancy aftercurative therapy

• Medical, psychological, or social condition that, in the opinion of theinvestigator, may increase the patient's risk or limit the patient's adherence withstudy requirements