Metastatic Breast Cancer Reclassified After NTRK Fusion Testing

What happened, in summary

A woman in her 40s was first diagnosed with stage IA microinvasive cancer in her right breast. An excision found ductal carcinoma in situ and 2 small foci of triple-negative invasive ductal carcinoma measuring 2.3 mm and 2.0 mm. Because the margins were close and the lymph nodes had not been sampled, she underwent a total mastectomy and sentinel lymph-node biopsy 1 month later. No residual cancer was found.

Six years later, a 1 cm cancer returned in the chest wall. She received 4 cycles of docetaxel and cyclophosphamide followed by chest-wall radiation. Five years after chemotherapy, scans found several new lung nodules. A biopsy confirmed metastatic breast cancer, with very low estrogen and progesterone receptor expression and negative HER2 results. She declined recommended chemotherapy and instead followed Gerson therapy based on organic foods, vegetable juices and numerous supplements.

The lung disease changed little at first, but over about 3.5 years it gradually progressed. A later scan showed that the lung and pleural disease had doubled, with new hilar, mediastinal and retrocaval lymph-node involvement. Repeat tissue testing found an ETV6-NTRK3 gene fusion. The same fusion was not detected in a circulating tumor DNA test.

Specialist review then showed that the cancer's appearance was consistent with secretory breast carcinoma rather than ordinary invasive ductal carcinoma. This reclassification explained its unusually slow course and created a targeted-treatment option. After starting larotrectinib, she had a rapid clinical and radiological response. Repeat tissue testing had identified an important target that the earlier blood-based test missed.