This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide 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. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.
STEP 1: REGISTRATION (SCREENING): Participants must have histologically confirmed estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (hormone receptor positive) and HER2 negative breast cancer, as per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines
NOTE: Participants with HER2 positive disease by ASCO CAP guidelines are ineligible. HER2 negative and HER2 low or equivocal cases as per ASCO CAP guidelines that do not receive HER2 targeted therapy are eligible
STEP 1: REGISTRATION (SCREENING): Participants must have clinical stage II or III breast cancer
NOTE: Participants with inflammatory breast cancer are eligible
None
Sequential
Biospecimen Collection
Procedure/SurgeryUndergo optional collection of tissue and/or blood
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven IV
Durvalumab
Biological/VaccineGiven IV
Genetic Testing
Other interventionUndergo MammaPrint testing
Mammography
Procedure/SurgeryUndergo mammography
Paclitaxel
DrugGiven IV
Quality-of-Life Assessment
Other interventionAncillary studies
Breast cancer event-free survival (BC-EFS)
Defined as the earliest occurrence of any of the following events: Local-regional or distant progression during neoadjuvant therapy or local/regional, or distant invasive breast tumor recurrence post-surgery, invasive ipsilateral breast tumor recurrence, new invasive contralateral breast cancer, or death from any cause. The primary analysis of BC-EFS is a log-rank test between the treatment arms with stratification by the three stratification factors. Additionally, Cox regression will be used to estimate the treatment hazard ratio and 95% confidence interval including the three stratification variables as terms in the model. Kaplan-Meier graphs will show BC-EFS descriptively over time and provide 5-year estimates and 95% confidence intervals. A forest plot will show whether the treatment effect varies over the stratification variables and other selected factors.
Pathologic complete response (pCR) rates
Defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast and specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/Tis ypN0). At the completion of all treatment and surgery for all enrolled participants, there will be a comparison of pCR rates between the treatment arms. pCR rates will be compared by a test of two proportions followed by logistic regression to estimate the odds ratio after adjustment for the stratification factors.
Residual cancer burden (RCB)
Defined as a continuous measure of the extent of residual cancer after neoadjuvant chemotherapy that combines the largest diameter of the cancer in the breast, the tumor cell cellularity of the cancer, and the largest diameter and number of involved axillary lymph nodes into a single RCB score. RCB will be analyzed by comparing RCB 2-3 to RCB 0-1.
Distant relapse-free survival (DRFS)
Analyses will be performed using log-rank testing, Cox regression, and Kaplan-Meier estimation.
Overall survival (OS)
Analyses will be performed using log-rank testing, Cox regression, and Kaplan-Meier estimation. Will also be conducted at alpha = 0.05 (2-sided).
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