The utility of using genomic testing on needle core biopsies during the COVID-19 pandemic: Molecular characterization, risk stratification, neoadjuvant outcome, and future implications

ABSTRACT

Introduction: The COVID-19 pandemic has caused an extraordinary challenge for global health. New guidelines were implemented, including postponing non-essential surgical procedures to conserve resources. In response, the COVID19 Pandemic Breast Cancer Consortium expert opinion suggested the use of core biopsies for genomic testing to help triage patients for surgical vs. systemic treatment. To better understand how expedited genomic results could impact peri-operative care, we performed a pre-operative quality project to assess testing Mammaprint (MP), a 70-gene risk of recurrence assay, and Blueprint (BP), an 80-gene molecular subtyping assay, on core biopsies. Here we report our experience with MP and BP testing on core biopsies, and the correlation between test results and response to neoadjuvant therapy.Design: From April to December 2020, all core biopsies with a breast carcinoma diagnosis from our clinic (300 patients) were routinely sent for MP and BP testing as part of a rapid result program that was initiated to see whether test results could be obtained in time and whether they would lead to more informed pre-operative treatment decisions. Unstained slides were sent for genomic and receptor testing concurrently. When genomic results differed from IHC/FISH results or suggested a different S treatment plan vs. clinical factors alone, we referred to this as "reclassification." For those patients who completed their neoadjuvant chemotherapy, we grouped them by their genomic results and by their conventional IHC/FISH/Clinical classification, and compared the outcome. Results: MP and BP results from core biopsy were available for 96.6% of patients (n=290/300). The average time from biopsy to test results was 10 days, and the average lab turnaround time was 5 days. Results were available for tumor conference discussions 100% of the time. MP and BP re-classified 84 of 300 patients (28%) from conventional IHC/FISH subtyping, and reclassified 42 of 195 patients (22%) of patients from their risk category based on traditional clinical factors (Table-1). Of the 38 patients with available post-neoadjuvant therapy outcome, 13 patients (34%) achieved pathologic complete response (pCR). 16 patients were classified as Her-2 enriched by IHC/FISH of which 9 (56%) achieved pCR. MP/BP aligned with the IHC/FISH Her-2 enriched classification in 11/16 patients, while 5 patients were reclassified to Luminal B by MP/BP. Of the 11 patients with concordant IHC/FISH and MP/BP results, 8 achieved pCR (73%), while one of the 5 cases reclassified to Luminal B achieved pCR (20%). Of the patients who were classified Luminal by IHC (9 patients), one patient achieved pCR (11%), and of the patients classified luminal (A or B) by MP/BP (12 patients) two achieved pCR (16%). Of the IHC-triple negative patients and genomic basal patients, three patients achieved pCR in each group (23% and 20%, respectively). Conclusion: Performing MP/BP tests on core needle biopsies hold a high success rate. Incorporating test results into peri-operative discussions may result in better-informed decisions about treatment planning and timing of surgery versus systemic therapy. A higher rate of pCR was seen in the MP/BP Her-2 enriched group compared to the IHC/FISH Her-2 enriched group. Although this workflow was designed to triage patients during the COVID pandemic, this approach has great potential beyond the pandemic.