This study aims to utilize a novel biomarker-driven approach to guide neoadjuvant treatment selection. It is the hypothesis that this will improve clinical response for postmenopausal women with clinical stage II/III ER-positive, HER2-negative breast cancer and identify those who may not require neoadjuvant chemotherapy, with a primary focus on outcomes in Black patients.
Histologically or cytologically confirmed newly diagnosed clinical stage II or III (by AJCC 8th edition - at least T2, any N, M0 or if N1+ then any T) ER-positive (ER > 10%), any PR, and HER2-negative breast cancer with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal.
HER2 negative must be assessed by FISH or IHC staining 0 or 1+ according to ASCO/CAP guidelines.
≥2 cm in one dimension by clinical or radiographic examination (WHO criteria), if clinically axillary lymph node negative OR
Measureable (≥10 mm) by modified RECIST v1.1 for breast MRI (see Section 9.0), if histologically confirmed resectable locoregional nodal involvement.
Inflammatory breast cancer (cT4d disease as per AJCC 8th edition).
Locally recurrent or metastatic disease (cM1 disease as per AJCC 8th edition).
Bilateral breast cancer.
Prior systemic therapy for the indexed breast cancer.
Parallel
VENTANA MIB-1 Ki67 assay
DeviceKi67 scoring determination (standard of care) utilizing the Ki67 MIB-1 assay (clone 30-9) (VENTANA) will be performed at baseline, Week 4 (+/- 14 days - high-risk group only), and at time of surgery in accordance with the International Ki67 in Breast Cancer Working Group guidelines.
Oncotype DX® Recurrence Score
DeviceOncotype DX® Recurrence Score (RS) testing - assessing expression of 21 genes including 16 cancer-related genes and 5 reference genes - will be performed as standard of care in a central laboratory (Exact Sciences) on RNA extracted from formalin-fixed paraffin-embedded core-biopsy samples.
PAM50-based Prosigna breast cancer gene signature assay
DeviceThis PAM50-based Prosigna breast cancer gene signature assay for intrinsic molecular subtype determination will be performed on formalin-fixed, paraffin-embedded (FFPE) core-biopsy samples.
Anastrozole
DrugStandard of care. All patients must start on anastrozole at time of enrollment but may switch to another aromatase inhibitor (letrozole or exemestane) due to toxicity or financial/other concerns at discretion of investigator after a discussion with the PI. Every effort to minimize interruption of aromatase inhibitor (AI) therapy is recommended.
Combination anthracycline and/or taxane based treatment
DrugStandard of care
Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)
* ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to RECIST v1.1. * Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions thought to be non-malignant should be further investigated before CR can be accepted. * Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD.
Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment
Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment
Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group
* ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to modified RECIST v1.1. * Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions thought to be non-malignant should be further investigated before CR can be accepted. * Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD.
Objective response rate (ORR) by breast MRI in the high-risk endocrine-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole)
* ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to modified RECIST v1.1. * Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions thought to be non-malignant should be further investigated before CR can be accepted. * Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD.
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Washington University School of Medicine
Lead sponsor
Swim Across America
Collaborator
The Foundation for Barnes-Jewish Hospital
Collaborator
