Assessing the Accuracy of Tumor Biopsies After Chemotherapy to Determine if Patients Can Avoid Breast Surgery

Study Overview
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Brief Summary
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This phase II trial studies how well biopsy of breast after chemotherapy works in predicting pathologic response in patients with stage II-IIIA breast cancer undergoing breast conserving surgery. Tumor tissue collected from biopsy before surgery may help to check if chemotherapy destroyed the breast cancer cells and may be compared to the tumor removed during surgery to check if they are the same.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the accuracy of post-neoadjuvant systemic therapy (NST) image-directed tumor bed biopsy for pathologic complete response (pCR), defined as resolution of both invasive disease and ductal carcinoma in situ (DCIS), in cases of clinical and radiologic complete response with trimodality imaging. SECONDARY OBJECTIVES: I. To collect axillary pathology results, surgical staging methods (sentinel lymph node biopsy and/or axillary lymph node dissection), and management (surgery and/or radiation) in order to determine axillary nodal response to neoadjuvant chemotherapy and its relationship to breast pCR. II. To correlate imaging results with pathologic nodal status following neoadjuvant chemotherapy for future planning of axillary management in the next study. III. To retrospectively assess the negative predictive value (NPV) of a trimodality imaging algorithm in combination with the tumor bed biopsy for predicting pCR. IV. To collect all trimodality imaging data to determine which combination of the trimodality imaging best identifies the group achieving pCR. V. To correlate the number of needle cores and tumor bed clip retrieval with the NPV of the tumor site biopsy. VI. To determine the clinical, imaging, pathologic, and molecular tumor factors associated with the highest NPVs of post-NST tumor bed biopsies. VII. To improve identification and selection of patients with breast and possible axillary pCR for future trial planning, routine biomarkers (estrogen receptor [ER], progesterone receptor [PR], HER2 neu, and Ki67) will be collected to allow comparison to image/clinical complete response (CR), and tumor bed biopsies. OUTLINE: After completion of neoadjuvant therapy, patients undergo stereotactic biopsy of breast tumor any time prior to breast conserving surgery. Patients then undergo breast conserving surgery as per standard of care. Patients may also undergo postoperative radiation therapy per standard of care or adjuvant therapy at the investigator's discretion.

Official Title
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A Phase II Trial Assessing the Accuracy of Tumor Bed Biopsies in Predicting Pathologic Response in Patients With Clinical/Radiologic Complete Response After Neoadjuvant Chemotherapy in Order to Explore the Feasibility of Breast Conserving Treatment Without Surgery

Conditions
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Invasive Breast Carcinoma, Stage II Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer

Intervention / Treatment
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* Procedure: Biopsy of Breast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients must have had ER analysis performed on the primary breast tumor collected prior to neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients who have a primary tumor that is hormone receptor-positive or hormone receptor-negative are eligible. Patients must have had HER2 testing performed on the primary breast tumor collected prior to neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer; patients who have a primary tumor that is HER2-positive, HER2-equivocal, or HER2-negative are eligible Patients must have had a biopsy marker placed within the tumor bed with imaging confirmation (preferably mammogram but ultrasound or magnetic resonance imaging [MRI] is acceptable) of marker placement prior to neoadjuvant chemotherapy Patients with operable focal or multifocal (T1-T3, stage II or III invasive ductal carcinoma [all receptor phenotypes]), and who have completed neoadjuvant chemotherapy with a clinical complete response (by clinical examination) Patients with synchronous bilateral breast cancer are eligible if at least one of the synchronous breast cancers has a cCR, and the side with a cCR meets criteria. (Patients with previous contralateral invasive breast cancer treated with anti-cancer therapy are eligible.) Patients must have achieved a complete or near complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI during or after completion of appropriate neoadjuvant chemotherapy defined as: Mammogram with malignant appearing calcification or mass ≤ 1 cm; or Ultrasound with a hypoechoic area ≤ 2 cm; or Breast MRI not demonstrating a residual mass with rapid rise and washout type III kinetics. At the time of consent, the patient's intent must be to undergo breast conserving therapy. Patient must be able to undergo stereotactic-vacuum-assisted breast biopsy with clip placement after completion of neoadjuvant chemotherapy. (The patient must be enrolled on the study before performing the post-neoadjuvant stereotactic-vacuum-assisted breast biopsy.) Patient must have completed neoadjuvant chemotherapy. Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated. Patients treated with PD-1 or PD-L1 inhibitors, CDK 4/6 inhibitors, or other immune-based therapy are eligible. Exclusion Criteria: T4 tumors including inflammatory breast cancer Patients with distant metastatic disease Lumpectomy performed prior to study entry Patients with any history of prior radiation therapy in the affected breast Patients with a prior history of ipsilateral invasive breast cancer; (patients with previous ipsilateral/contralateral DCIS or previous contralateral invasive breast cancer treated with anti-cancer therapy are eligible) Patients with invasive lobular carcinoma Patients who have multicentric disease Patients treated with neoadjuvant hormonal therapy only are not eligible Patients who are medically unfit to undergo surgical resection Patients without breast biopsy marker documented by imaging at tumor bed site prior to initiation of neoadjuvant therapy Patients with one or more of the following imaging criteria from any of the 3 imaging modalities after completion of NCT demonstrating incomplete radiologic response are not eligible: Mammogram with malignant appearing calcifications or mass > 1 cm; or Ultrasound with a hypoechoic area > 2 cm; or Breast MRI demonstrating a residual mass with rapid rise and washout type III kinetics. Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results Pregnancy or lactation at the time of study registration; (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study registration.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (biopsy of breast)<br>After completion of neoadjuvant therapy, patients undergo stereotactic biopsy of breast tumor any time prior to breast conserving surgery. Patients then undergo breast conserving surgery as per standard of care. Patients may also undergo postoperative radiation therapy per standard of care or adjuvant therapy at the investigator's discretion. | Procedure: Biopsy of Breast<br>* Undergo stereotactic biopsy<br>* Other names: Breast Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with pCR | The proportion of tumor bed biopsies that are negative among those who are shown to have pCR at surgery will be determined. The point estimate and 95% confidence interval will be calculated. | Up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of negative predictive value | Analysis will be performed to assess the improvement in the negative predictive value of the trimodality imaging algorithm when the results of tumor bed biopsy are added. | Up to 18 months | 
| Incidence of adverse events associated with tumor bed biopsy | Descriptive analysis will be performed to determine the frequencies of adverse events associated with tumor bed biopsy. | Up to 18 months | 
| Number of needle cores performed | Descriptive analysis will be performed to determine the distribution of the number of needle cores performed and the proportion of clips retrieved. | Up to 18 months | 
| Proportion of clips retrieved | Descriptive analysis will be performed. | Up to 18 months | 
| Residual cancer burden score | Descriptive analysis will be performed to determine the distribution of residual cancer burden score. | Up to 18 months | 
| Trimodality imaging algorithm +/- biopsy as a predictor of pCR | Analysis will be performed to assess the improvement in the negative predictive value of the trimodality imaging algorithm when the results of tumor bed biopsy are added. | Up to18 months |