NeoTAILOR: ABiomarker-directed Approach to Guide Neoadjuvant Therapy for Patients With Stage II/III ER-positive, HER2-negative Breast Cancer

NeoTAILOR: A Phase II Biomarker-directed Approach to Guide Neoadjuvant Therapy for Patients With Stage II/III ER-positive, HER2-negative Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Cancer of the Breast
• Intervention / Treatment: Device: VENTANA MIB-1 Ki67 assay; Device: Oncotype DX® Recurrence Score; Device: PAM50-based Prosigna breast cancer gene signature assay; Drug: Combination anthracycline and/or taxane based treatment; Drug: Anastrozole

Detailed Description

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
• Enrollment (Estimated): 81
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nusayba A Bagegni, M.D.; Phone Number: 314-273-3022; Email: nbagegni@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Cynthia X Ma, M.D., Ph.D.
      • Sub-Investigator: Ian Hagemann, M.D., Ph.D.
      • Contact: Nusayba A Bagegni, M.D.; Phone Number: 314-273-3022; Email: nbagegni@wustl.edu
      • Principal Investigator: Nusayba A Bagegni, M.D.
      • Sub-Investigator: Emily L Podany, M.D.
      • Sub-Investigator: Debbie L Bennett, M.D.
      • Sub-Investigator: John Olson, M.D., Ph.D.
      • Sub-Investigator: Katherine Glover-Collins, M.D., Ph.D.
      • Sub-Investigator: Fouad Boulos, M.D.
      • Sub-Investigator: Carolina Salvador, M.D.
      • Sub-Investigator: Jingqin (Rosy) Luo, Ph.D.
      • Sub-Investigator: Katherine Weilbaecher, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

• A palpable mass is not required; however, tumor size must be either:

  • ≥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.
• ECOG performance status 0 or 1.
• Eligible to receive neoadjuvant aromatase inhibitor, as per treating physician.
• Eligible to receive neoadjuvant standard of care anthracycline- and/or taxane-based chemotherapy regimen, as per treating physician.
• Able to tolerate breast MRI with intravenous contrast administration. Must be able to complete the applicable MRI screening evaluation form.
• Adequate bone marrow and organ function, as determined by the treating physician.
• Known history of hepatitis C virus (HCV) infection is permissible provided the patient has been treated and cured.
• At least 18 years of age.

• Postmenopausal status, defined as one of the following:

  • Age ≥ 60 years
  • Age < 60 with intact uterus and amenorrhea for 12 consecutive months or more
  • Status post bilateral oophorectomy, total hysterectomy
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable), and willing and able to comply with scheduled visits and treatment schedule.

Exclusion Criteria:

• 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.
• Pre-existing Grade ≥2 neuropathy.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.

• A history of other malignancy ≤5 years prior to the indexed breast cancer diagnosis with the following exceptions:

  • Basal cell or squamous cell carcinoma of the skin which were treated with local resection only
  • Adequately treated carcinoma in situ of the cervix.
  • Prior or concurrent malignancy whose natural history or treatment will not interfere with the safety or efficacy assessments of the indexed breast cancer. In this event, review and approval by the study PI is required.
• Concurrent participation in any investigational therapeutic trial for treatment of breast cancer.
• Known HIV positivity that in the judgement of the treating physician would impact safety of chemotherapy receipt.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to anastrozole, taxanes (paclitaxel or nab-paclitaxel), anthracyclines (doxorubicin or epirubicin) or cyclophosphamide.
• Evidence of uncontrolled ongoing or active infection, requiring parenteral anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to administration of study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• Any uncontrolled medical condition that in the opinion of the Investigator would pose a risk to participant safety or interfere with study participation or interpretation of individual participant results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-risk group; Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.; An additional blood draw for research purposes at Week 4 (no breast tumor biopsy at this time point) and continue to receive 5 additional 28-day cycles of anastrozole.; After completion of ~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.	Device: VENTANA MIB-1 Ki67 assay; 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.; Device: Oncotype DX® Recurrence Score; 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.; Device: PAM50-based Prosigna breast cancer gene signature assay; 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.; Drug: Anastrozole; 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.
Experimental: High-risk endocrine-sensitive group; Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.; An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 ≤10% (the high-risk endocrine-sensitive group) will continue to receive 5 additional 28-day cycles of anastrozole.; After completion of ~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.	Device: VENTANA MIB-1 Ki67 assay; 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.; Device: Oncotype DX® Recurrence Score; 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.; Device: PAM50-based Prosigna breast cancer gene signature assay; 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.; Drug: Anastrozole; 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.
Experimental: High-risk endocrine-resistant group; Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50.; An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 >10% (the high-risk endocrine-resistant group) will receive escalated therapy with ~5-6 additional months of standard of care chemotherapy (combination anthracycline- and/or taxane-based at the discretion of their physician).; After completion of ~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.	Device: VENTANA MIB-1 Ki67 assay; 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.; Device: Oncotype DX® Recurrence Score; 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.; Device: PAM50-based Prosigna breast cancer gene signature assay; 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.; Drug: Combination anthracycline and/or taxane based treatment; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through completion of treatment (estimated to be 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment		Through completion of surgery (estimated to be 6 months)
Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment		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.	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.	Through completion of treatment (estimated to be 6 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Foundation for Barnes-Jewish Hospital; Swim Across America
• Investigators: Principal Investigator: Nusayba Bagegni, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; postmenopausal women; Ki67; PAM50 subtype; breast cancer disparities
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nitriles; Triazoles; Anastrozole
• Other Study ID Numbers: 202305007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No