This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in treating patients with previously untreated breast cancer. Drugs used in chemotherapy, such as paclitaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, may block tumor growth in different ways by targeting certain cells. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVES: I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed by maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage T1cN0 and II-III breast cancer patients. II. To determine the pathological complete response rate (pCR) of this treatment regimen. III. To identify possible gene expression profile signatures from whole genome array analysis that correlate with clinical response/resistance to chemotherapy as measured by pathologic complete response rate (pCR). OUTLINE: NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without metastasis undergo mastectomy or breast conserving surgery 4-8 weeks later. POST-SURGERY/SYSTEMIC THERAPY: HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy. STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy. STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard radiation therapy. After completion of study treatment, patients are followed up every 3 months for 2 years, and then annually thereafter for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Given IV
Given IV
Correlative studies
Given IV
Undergo RT
Undergo mastectomy or breast conserving surgery
Given IV
Nebraska Medicine-Bellevue
Bellevue, Nebraska, United States
CHI Health Saint Francis
Grand Island, Nebraska, United States
Nebraska Medicine-Village Pointe Cancer Center
Omaha, Nebraska, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Overall Incidence of Toxicities, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Number of participants in each subset (Her2 positive and Her2 negative) who experience at least one adverse event \[overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\].
Time frame: Up to 30 days after completion of study treatment, maximum of 114 days
Overall Severity of Toxicities, Graded According to the NCI CTCAE Version 4.0
Results reported as total events per grade for human epidermal growth factor receptor 2 (HER2)negative and HER2 positive (Overall severity of toxicities, graded according to the NCI CTCAE version 4.0).
Time frame: Up to 30 days after completion of study treatment, maximum of 114 days
Number of Participants in the Subgroups Who Had a Pathologic Complete Response (pCR)
The number of participants in the subgroups who had a pathologic complete response (pCR) determined from the surgical specimen and defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ.
Time frame: Up to 12 weeks (after the first 6 courses of treatment), maximum of 168 days
Clinical Complete Response
The absence of all detectable cancer after treatment is complete.
Time frame: Up to 2 years
Failure-free Survival (FFS)
The analysis will be based on Kaplan-Meier estimates. FFS will be summarized overall and for human epidermal growth factor receptor 2 (HER2)+ and HER- subsets.
Time frame: The time from the date of administration of study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 2 years
Identification of Gene Expression Profile Signatures That Correlate With Clinical Response as Measured by pCR
The number of the identified mutated genes, the frequency of each gene being validated by reverse transcriptase-polymerase chain reaction (RT-PCR)/Sanger sequencing method, and the functions of these identified genes will be descriptively summarized.
Time frame: Up to 2 years
Overall Survival (OAS)
The analysis will be based on Kaplan-Meier estimates. OAS will be summarized overall and for HER+ and HER- subsets.
Time frame: The time from the date of the date of administration of study drug to the date of death from any cause, assessed up to 2 years
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