Biomarker NTRK Coverage from Every Angle

Rare Case of Recurrent Secretory Carcinoma of the Breast With NTRK3 Gene Fusion

By: Julia Fiederlein
Posted: Tuesday, September 14, 2021

Most secretory carcinomas of the breast represent slow-growing tumors with favorable outcomes. A rare case of such a tumor with NTRK3 gene fusion, which was described in The Oncologist, recurred within 1 year of surgery. Aditya Bardia, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues reviewed the molecular findings and potential clinical significance.

“Approval of TRK inhibitors necessitates optimization of NTRK [gene] fusion detection assays,” the investigators commented. “Anchored multiplex polymerase chain reaction [AMP] uniquely assesses for possible [gene] fusions by targeting one commonly involved fusion partner regardless of the identity of the other fusion partner and was used to identify the ETV6-NTRK3 [gene] fusion in the case…reported here.”

A 46-year-old premenopausal woman was diagnosed with an invasive ductal carcinoma of the left breast. A multigene germline panel test did not identify any mutations. After experiencing minimal response to neoadjuvant chemotherapy, she underwent left lumpectomy; invasive secretory carcinoma of the breast and secretory and nonsecretory ductal carcinoma in situ were found. After re-excision, a completion left mastectomy revealed residual invasive secretory carcinoma and secretory ductal carcinoma in situ. Adjuvant tamoxifen was initiated; however, the patient discontinued this treatment after 1 month.

Nearly 12 months after mastectomy, core biopsies revealed triple-negative invasive ductal carcinoma. The patient underwent excision of the mass and axillary lymph node dissection; triple-negative secretory carcinoma of the breast and a single small focus of ductal carcinoma in situ were found. Next-generation sequencing–based AMP using RNA input detected an ETV6-NTRK3 gene fusion in the initial surgical and recurrence specimens.

“Each fusion pair can have different breakpoints, and the NTRK genes contain large intronic regions that may not be covered by DNA-based next-generation sequencing panels,” the investigators explained. “As a whole, analyzing and detecting NTRK [gene] fusions require foresight and acknowledgment of the relative strengths and weaknesses of the various assays available.”

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