This randomized phase III trial studies docetaxel, carboplatin, trastuzumab, and pertuzumab with estrogen deprivation to see how they work compared to docetaxel, carboplatin, trastuzumab, and pertuzumab without estrogen deprivation in treating patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that is operable or has spread from where it started to nearby tissue or lymph nodes (locally advanced). Drugs used in chemotherapy, such as docetaxel, carboplatin, trastuzumab, and pertuzumab, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using goserelin acetate and aromatase inhibition therapy may fight breast cancer by blocking the use of estrogen by the tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. Giving combination chemotherapy and radiation therapy with or without hormone therapy may be an effective treatment for hormone receptor-positive, HER2-positive, operable or locally advanced breast cancer.
PRIMARY OBJECTIVES: I. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of therapy of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) yields a greater rate of pathologic complete response (pCR) (breast and nodes) than TCHP alone when administered to women with operable, hormone receptor-positive, HER2-positive breast cancer. SECONDARY OBJECTIVES: I. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP will increase the pCR rate in the breast compared to TCHP alone when administered to women with operable, hormone receptor-positive, HER2-positive breast cancer. II. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP improves recurrence-free interval (RFI) in women with operable, hormone receptor-positive, HER2-positive breast cancer. III. To determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of TCHP improves overall survival (OS) in women with operable, hormone receptor-positive, HER2-positive breast cancer. IV. To compare the rates of second primary invasive cancer by treatment arm. V. Assessment of patterns of pCR, RFI, and OS by menopausal status. VI. To evaluate the cardiac toxicity associated with each of the regimens. VII. To compare the effect of adding estrogen deprivation to neoadjuvant therapy on endocrine-related symptoms in all patients by treatment arm. VIII. To compare the effect of adding estrogen deprivation to neoadjuvant therapy on vasomotor symptoms, musculoskeletal, and vaginal complaints as well as quality of life. IX. To determine a relationship between pCR and a potential mechanism of resistance/sensitivity in hormone receptor-positive, HER2-positive tumors. X. To evaluate tumor infiltrating lymphocytes (TILs) and immune biomarkers as predictors of pCR. XI. To study early changes in TILs and other immune biomarkers in response to TCHP. OUTLINE: Patients are randomized to 1 of 2 treatments arms. NEOADJUVANT: ARM I: Patients receive docetaxel intravenously (IV) over 60 minutes, carboplatin IV over 30-60 minutes, trastuzumab IV over 30-90 minutes, and pertuzumab IV over 30-60 on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. ARM II: All patients receive docetaxel, carboplatin, trastuzumab, and pertuzumab as in arm I. Premenopausal patients also receive goserelin acetate subcutaneously (SC) every 28 days until surgery and aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Postmenopausal patients receive aromatase inhibition therapy at the investigator's discretion daily until 1 day before surgery. Patients enrolled after Amendment #4 undergo 2 core biopsies prior to course 3 of treatment. SURGERY: Patients undergo lumpectomy or mastectomy. RADIATION: Patients undergo whole breast irradiation within 8 weeks following surgery. ADJUVANT: Patients receive trastuzumab IV over 30-60 minutes every 21 days for up to 1 year. After completion of study treatment, patients are followed up every 6, 9, 12, and 18 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
315
Given at the investigator's discretion
Given IV
Undergo 2 core biopsies
Given IV
Given SC
Correlative studies
Given IV
Ancillary studies
Undergo lumpectomy or mastectomy
Given IV
Undergo whole breast irradiation
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, United States
PCR Oncology
Arroyo Grande, California, United States
Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes
Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy.
Time frame: Up to 2.8 years (when all patients completed primary breast surgery)
Percent of Patients With Pathologic Complete Response (pCR) in the Breast
Proportion of patients with pCR in the breast, defined as the absence of any invasive component in the resected breast specimen.
Time frame: Up to 2.8 years (when all patients completed primary breast surgery)
Recurrence Free Interval (RFI)
Kaplan-Meier estimates of the percentages of patients free from recurrence.
Time frame: Time from surgery to invasive local, regional or distant recurrence, or death from breast cancer for patients with operable disease and for patients with inoperable progressive disease, assessed up to 8.4 years
Overall Survival (OS)
Kaplan-Meier estimates of the percentages of patients surviving.
Time frame: Time from randomization until death from any cause, assessed up to 8.4 years
Rate of Second Primary Invasive Cancer of Any Type
The cumulative incidence rates of second primary cancers for the two treatment groups.
Time frame: Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 8.4 years
Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes by Menopausal Status
Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy calculated separately for premenopausal and postmenopausal women.
Time frame: Up to 2.8 years (when all patients completed primary breast surgery)
Patterns of Recurrence Free Interval (RFI) by Menopausal Status
Kaplan -Meier estimates of the percentages of patients free from recurrence by menopausal status.
Time frame: Up to 5 years
Patterns of Overall Survival (OS) by Menopausal Status
Kaplan-Meier estimates of the percentages of patients surviving by menopausal status.
Time frame: Up to 5 years
Percentage of Participants With Cardiac Toxicity Categorized According to National Cancer Institute CTCAE Version 4.0
Percentage of patients with grade 1 or higher toxicity from the Cardiac Disorders System Organ Class.
Time frame: Up to 6 weeks post surgery
Median Percentage of Tumor-infiltrating Lymphocytes (sTILS)
Percentage of Tumor-infiltrating lymphocytes present in the stroma in tissue specimen.
Time frame: 2.8 years
Change in Endocrine-related Symptoms Using Breast Cancer Prevention Trial (BCPT) Symptom Checklist
Mean total score from the BCPT symptom checklist calculated as the average severity score across all items at each timepoint.
Time frame: Baseline to up to 4 weeks after the last dose of chemotherapy
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Sutter Auburn Faith Hospital
Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California, United States
Kaiser Permanente-Bellflower
Bellflower, California, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
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