A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy
A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy
This randomized phase III trial studies lymph node dissection and radiation therapy to see how well it works compared to radiation therapy alone in treating patients with breast cancer previously treated with chemotherapy and surgery. Lymph node dissection may remove cancer cells that have spread to nearby lymph nodes in patients with breast cancer. Radiation therapy uses high-energy x rays or protons to kill tumor cells. It is not yet known if radiation therapy works better alone or with lymph node dissection in treating patients with breast cancer previously treated with chemotherapy and surgery.
PRIMARY OBJECTIVE:
I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive sentinel lymph node(s) (SLN[s]) after completion of neoadjuvant chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy.
II. To obtain an estimate of the distribution of residual disease burden scores.
III. To estimate the distribution of overall survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo axillary lymph node dissection. Beginning 3-12 weeks following surgery, patients undergo nodal radiation therapy comprising 3-dimensional (3D) conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton radiation therapy (PRT) 5 days a week for 5-6 weeks.
ARM II: Patients undergo axillary and nodal radiation therapy comprising 3D-CRT, IMRT, or PRT 5 days a week for 5-6 weeks.
After completion of study treatment, patients are followed up at least every 6 months for 2 years and then annually for 3 years.
Pre-Registration Eligibility Criteria:
Clinical stage T1-3 N1 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging 7th edition
No inflammatory breast cancer
No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix
All patients must have had an axillary ultrasound with fine needle aspiration (FNA) or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to or at most 14 days after starting neoadjuvant chemotherapy
* Note: Biopsy of intramammary nodes does not fulfill eligibility criteria
Patients must have had estrogen receptor, progesterone receptor and HER2 status (by immunohistochemistry [IHC] and/or in situ hybridization [ISH]) evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy
* Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled
Patients must have completed all planned neoadjuvant chemotherapy prior to surgery; sandwich chemotherapy is not allowed (i.e. anthracycline/cytoxan or taxane chemotherapy planned to be given after surgery); patients must have completed at least 4 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen without evidence of disease progression in the breast or the lymph nodes
* Note: Delays/dose modifications due to toxicities/adverse events are allowed as long as a minimum of 4 cycles of neoadjuvant chemotherapy is administered; more than 4 cycles of neoadjuvant chemotherapy (NAC) may be administered at the discretion of the treating medical oncologist
Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, or trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen); therapy must be Food and Drug Administration (FDA)-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an Institutional Review Board (IRB)-approved clinical trial
All patients must have a clinically negative axilla (no bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy
* Note: an ultrasound of the axilla is not required at completion of neoadjuvant chemotherapy; if performed, its findings do NOT impact eligibility
No more than 8 weeks of neoadjuvant endocrine therapy prior to the start of neoadjuvant chemotherapy
No neoadjuvant radiation therapy
No SLN surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy
No prior history of ipsilateral breast cancer (invasive disease or ductal carcinoma in situ [DCIS]); lobular carcinoma in situ (LCIS) and benign breast disease is allowed
No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis
No history of prior or concurrent contralateral invasive breast cancer; benign breast disease; LCIS or DCIS of contralateral breast is allowed
Patients must not be pregnant or nursing
* Note: Peri-menopausal women must be amenorrheic for > 12 months to be considered not of childbearing potential
Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
Intra-Operative Registration/Randomization Criteria:
Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of the last dose of neoadjuvant chemotherapy
A minimum of 1 sentinel node and a maximum of 8 total nodes (sentinel + non-sentinel) are identified and excised; more than 8 nodes identified by either surgeon or pathologist is NOT allowed Note: Patients who do not have an identifiable sentinel lymph node will not proceed to registration/randomization
At least one lymph node (sentinel or non-sentinel) excised during sentinel lymph node surgery with a metastasis greater than 0.2 mm in greatest dimension identified on intra-operative pathologic assessment
Post-Operative Registration/Randomization Criteria:
Jonesboro, Arkansas 72401, United States
Burbank, California 91505, United States
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Sacramento, California 95817, United States
San Pablo, California 94806, United States
Vacaville, California 95687, United States
Highland Park, Illinois 60035, United States
Pekin, Illinois 61554, United States
Louisville, Kentucky 40202, United States
Baltimore, Maryland 21237, United States
South Weymouth, Massachusetts 02190, United States
Brownstown, Michigan 48183, United States
East China Township, Michigan 48054, United States
Grosse Pointe Woods, Michigan 48236, United States
Macomb, Michigan 48044, United States
Norton Shores, Michigan 49444, United States
Rochester Hills, Michigan 48309, United States
Warren, Michigan 48093, United States
West Branch, Michigan 48661, United States
Columbus, Mississippi 39705, United States
New Albany, Mississippi 38652, United States
North Kansas City, Missouri 64116, United States
Las Vegas, Nevada 89109, United States
Las Vegas, Nevada 89113, United States
Las Vegas, Nevada 89149, United States
New Brunswick, New Jersey 08903, United States
New York, New York 10032, United States
Wilmington, North Carolina 28401, United States
Wilmington, North Carolina 28401, United States
Harrisburg, Pennsylvania 17109, United States
Lancaster, South Carolina 29720, United States
American Fork, Utah 84003, United States
Berlin Corners, Vermont 05602, United States
Spokane, Washington 99204, United States
Spokane, Washington 99218, United States
Spokane Valley, Washington 99216, United States
Yakima, Washington 98902, United States
Milwaukee, Wisconsin 53210, United States
Summit, Wisconsin 53066, United States
Saint John, New Brunswick E2L 4L2, Canada
Montreal, Quebec H3H 2R9, Canada