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

 -  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.)