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.
Risk category is defined as follows: * Low risk: * Baseline Ki67 ≤ 10% (OR) * Luminal A molecular intrinsic subtype by PAM50 * High risk: * Non-Luminal A molecular intrinsic subtype by PAM50 (OR) * In cases of non-diagnostic PAM50 molecular intrinsic subtype, patients will enroll in the high-risk group and undergo Week 4 tumor biopsy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
81
Ki67 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 (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.
This 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.
Standard 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.
Standard of care
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGObjective 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.
Time frame: Through completion of treatment (estimated to be 6 months)
Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment
Time frame: Through completion of surgery (estimated to be 6 months)
Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment
Time frame: Through completion of surgery (estimated to be 6 months)
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.
Time frame: Through completion of treatment (estimated to be 6 months)
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.
Time frame: Through completion of treatment (estimated to be 6 months)
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