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

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 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 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 and IIIA invasive ductal
carcinoma [all receptor phenotypes]), and who have completed neoadjuvant chemotherapy
with a clinical complete response (by clinical examination)

- Patients must have achieved a complete or near complete radiologic tumor response on
breast imaging with mammogram, ultrasound, and MRI

- Patients must be undergoing breast conserving therapy

- Patient must be able to undergo stereotactic-vacuum-assisted breast biopsy with clip
placement after completion of neoadjuvant chemotherapy

- Patient must have completed a minimum of 8 weeks of standard neoadjuvant chemotherapy
consisting of an anthracycline and/or taxane-based regimen

- 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

- Patients with previous contralateral invasive breast cancer treated with anti-cancer
therapy are eligible

Exclusion Criteria:

- T4 tumors including inflammatory breast cancer

- Patients with metastatic disease

- Lumpectomy performed prior to study entry

- Patients with any history of prior radiation therapy in the affected breast

- Patients with synchronous ipsilateral invasive breast cancer or any 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 who did not undergo trimodality imaging after completion of neoadjuvant
chemotherapy (breast ultrasound, MRI, and mammography)

- Patients with one or more of the following imaging criteria from any of the 3 imaging
modalities after completion of neoadjuvant chemotherapy (NCT) 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)