A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients with Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

Protocol # :
Stage IB Breast Cancer
Stage II Breast Cancer
Disease Sites
Principal Investigator
Nakhlis, Faina
Site Investigator
Ho, Alice
Site Research Nurses
Casella, Allison
Germon, Victoria
Kasparian, Elizabeth
Lehnus, Jaclyn
Marchetti, Kelly
Wong, Christine

Trial Description

This randomized phase III trial studies standard or comprehensive radiation therapy in
treating patients with early-stage breast cancer who have undergone surgery. Radiation
therapy uses high-energy x rays to kill tumor cells. It is not yet known whether
comprehensive radiation therapy is more effective than standard radiation therapy in treating
patients with breast cancer

Eligibility Requirements

Inclusion Criteria:

- The patient must have signed and dated an Institutional Review Board (IRB)-approved
consent form that conforms to federal and institutional guidelines

- The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1

- Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before
neoadjuvant therapy); clinical axillary nodal involvement can be assessed by
palpation, ultrasound, CT scan, magnetic resonance imaging (MRI), positron emission
tomography (PET) scan, or PET/CT scan

- Patient must have had pathologic confirmation of axillary nodal involvement at
presentation (before neoadjuvant therapy) based on either a positive fine needle
aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy
(demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be
performed either by palpation or by image guidance; documentation of axillary nodal
positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted

- Patients must have had estrogen receptor (ER) analysis performed on the primary breast
tumor before neoadjuvant therapy according to current American Society of Clinical
Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for
hormone receptor testing; if negative for ER, assessment of progesterone receptor
(PgR) must also be performed according to current ASCO/CAP guideline recommendations
for hormone receptor testing (http://www.asco.org)

- Patients must have had HER2 testing performed on the primary breast tumor before
neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations
for human epidermal growth factor receptor 2 testing in Breast Cancer
(http://www.asco.org); patients who have a primary tumor that is either HER2-positive
or HER2-negative are eligible

- Patient must have completed a minimum of 8 weeks of standard neoadjuvant chemotherapy
consisting of an anthracycline and/or taxane-based regimen

- For patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks of
intended chemotherapy may be administered but must be completed before randomization;
(if treatment delays occur, chemotherapy must be completed within 14 weeks); the dose
and schedule of the adjuvant chemotherapy are at the investigator's discretion; Note:
It is preferred that all intended chemotherapy be administered in the neoadjuvant

- Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy
(either with all or with a portion of the neoadjuvant chemotherapy regimen), unless
medically contraindicated

- At the time of definitive surgery, all removed axillary nodes must be histologically
free from cancer; acceptable procedures for assessment of axillary nodal status at the
time of surgery include:

- Axillary node dissection

- Sentinel node biopsy alone or

- Sentinel node biopsy followed by axillary node dissection

- Note: Patients are eligible whether there is residual invasive carcinoma in the
surgical breast specimen or whether there is evidence of pathologic complete
response; patients who are found to be pathologically node-positive at the time
of surgery, based on sentinel node biopsy alone, are candidates for A011202, a
study developed by the Alliance in Oncology, an NCI Cooperative Group; if A011202
is open at the investigator's institution, patients should be approached about
participating in the A011202 study

- Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible (Note:
Postneoadjuvant therapy is designated with a "yp" prefix.)

- Patient who have undergone either a total mastectomy or a lumpectomy are eligible

- For patients who undergo lumpectomy, the margins of the resected specimen or
re-excision must be histologically free of invasive tumor and DCIS as determined by
the local pathologist; additional operative procedures may be performed to obtain
clear margins; if tumor is still present at the resected margin after re-excision(s),
the patient must undergo total mastectomy to be eligible; (patients with margins
positive for lobular carcinoma in situ [LCIS] are eligible without additional

- For patients who undergo mastectomy, the margins must be histologically free of
residual (microscopic or gross) tumor

- The interval between the last surgery for breast cancer (including re-excision of
margins) and randomization must be no more than 70 days; also, if adjuvant
chemotherapy was administered, the interval between the last chemotherapy treatment
and randomization must be no more than 70 days

- The patient must have recovered from surgery with the incision completely healed and
no signs of infection

- If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may
interfere with delivery of radiation therapy should have resolved

Exclusion Criteria:

- Definitive clinical or radiologic evidence of metastatic disease

- T4 tumors including inflammatory breast cancer

- Documentation of axillary nodal positivity before neoadjuvant therapy by sentinel node
biopsy alone

- N2 or N3 disease detected clinically or by imaging

- Patients with histologically positive axillary nodes post neoadjuvant therapy

- Patients with microscopic positive margins after definitive surgery

- Synchronous or previous contralateral invasive breast cancer or DCIS; (patients with
synchronous and/or previous contralateral LCIS are eligible)

- Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy; (patients with synchronous
or previous ipsilateral LCIS are eligible)

- History of non-breast malignancies (except for in situ cancers treated only by local
excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior
to randomization

- Any radiation therapy for the currently diagnosed breast cancer prior to randomization

- Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone
replacement therapy; patients are eligible if these medications are discontinued prior
to randomization

- Prior breast or thoracic radiation therapy (RT) for any condition

- Active collagen vascular disease, specifically dermatomyositis with a creatinine
phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus
erythematosus, or scleroderma

- Pregnancy or lactation at the time of study entry; (Note: Pregnancy testing must be
performed within 2 weeks prior to randomization according to institutional standards
for women of childbearing potential)

- Other non-malignant systemic disease that would preclude the patient from receiving
study treatment or would prevent required follow-up

- Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements