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

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.)