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
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
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.
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.
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:
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:
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.)
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Vacaville, California 95687, United States
Brownstown, Michigan 48183, United States
New Brunswick, New Jersey 08903, United States
Harrisburg, Pennsylvania 17109, United States
Summit, Wisconsin 53066, United States
Montreal, Quebec H3H 2R9, Canada