Breast biopsies after neoadjuvant chemotherapy accurately predict presence of residual breast cancer

Protocol identifies breast cancer patients for study in which surgery may be eliminated

Abstract: GS5-04

Researchers from The University of Texas MD Anderson Cancer Center have identified a standardized protocol that uses image-guided breast biopsies to reliably predict residual disease in breast cancer patients and that potentially identifies exceptional responders who may not require surgery. Utilizing this technique, a multicenter clinical trial led by Henry Kuerer, M.D., Ph.D., professor of Breast Surgical Oncology, is studying the elimination of surgery in exceptional responders after neoadjuvant chemotherapy (NAC).

Pooled analysis results of this technique derived from patient data at the Royal Marsden Hospital, Seoul National University Hospital and MD Anderson were presented today at the 2019 San Antonio Breast Cancer Symposium.

Data analyzed from 166 women in the study showed that the cancer could be completely eradicated with NAC given first, also called overall pathologic complete response (pCR) in 51.2%. This high rate of pCR suggests that many patients may not benefit from surgery if the cancer already is eradicated. When the image-guided biopsy was representative, the false negative rate (FNR) across the whole cohort was 18.7%.

However, when using MD Anderson criteria for selection of patients to study the safety of eliminating breast cancer surgery, the analysis of accuracy of vacuum assisted biopsies in cases with a residual imaging abnormality of < 2 centimeters to allow adequate sampling and at least six representative biopsies taken (n=76) showed an FNR of 3.2%, a negative predictive value (NPV) of 97.4% and an overall accuracy of 89.5%. These findings suggest an optimal post-NAC biopsy protocol to support omitting surgery and the ability to accurately predict residual cancer.

“For many breast cancer patients who need chemotherapy to increase survival, giving it first can completely kill the cancer. This finding motivated us to find an accurate way to identify these patients to study the safety of eliminating surgery in our ongoing clinical trial. The key finding from this multicenter trial illustrates that we must be super selective regarding the specific patient population to study this new paradigm,” said Kuerer. “This research suggests a standardized protocol may be able to eventually eliminate surgery in a select group of patients, while also closely and accurately monitoring their cancer for recurrence.”

The majority (n=160) of patients in the analysis had invasive ductal carcinoma (IDC) with phenotype distribution of 18.7% (n=31) hormone receptor (HR) positive/human epidermal growth factor receptor (HER) 2 negative, 28.3% (n=47) HR and HER2 positive, 17.5% (n=29) HR negative/HER2 positive and 35.5% (n=59) triple negative (TN) breast cancer.

A subgroup analysis in patients with HER2 positive or TN cancer (n=66) who are most likely to be exceptional responders and achieve pCR showed similar accuracy of the technique with an FNR of 4.2%, an NPV of 97.2% and an overall accuracy of 87.9%.

Median tumor size on pre-treatment imaging was 33.5 mm (range: 12 – 100) and median number of samples was 6 (range: 2 – 18). The biopsy was performed under ultrasound (n=129) or stereo guidance (n=37) and in 159 cases was representative of the tumor bed.

“This data shows that through image-guided vacuum assisted biopsies on patients who achieve a complete pathologic response to chemotherapy, accurate predictions of residual disease can be made, opening the door for potential avoidance of surgery,” said Kuerer. “This would be a major step toward improving quality of life for patients with breast cancer.”

Future additional studies will be designed to deescalate treatment in NAC-exceptional responders and study the safety of eliminating surgery for this select patient population.

The study was supported by the National Cancer Institute and the PH and Fay Eta Robinson Distinguished Professorship Endowment.

Kuerer reports disclosures of royalties from McGraw-Hill Professional Inc. and UpToDate Inc., employment by the NEJM Group, Inc., and consultancy for Genomic Health Inc.

A full list of collaborating researchers is included in the abstract.