Targeted Next-Generation Sequencing Reveals Clinically Actionable BRAF and ESR1 Mutations in Low-Grade Serous Ovarian Carcinoma

Low-grade serous ovarian cancer (LGSOC) is a rare (< 5%) subset of epithelial ovarian cancer with unique biologic, clinical, and genetic features.1 Compared with those with high-grade SOC (HGSOC), the most common histologic subtype of ovarian cancer, patients with LGSOC are diagnosed at a younger age and have a better prognosis.2,3 Standard-of-care treatment of advanced-stage LGSOC and HGSOC is similar: surgical cytoreduction plus platinum and taxane chemotherapy.4 However, LGSOC is less responsive to platinum-based chemotherapy compared with HGSOC,5,6 possibly because of slower proliferation and fewer abnormalities in the homologous recombination repair pathway (including BRCA1 or BRCA2 mutations) in LGSOC.7 In contrast, LGSOC may benefit more from endocrine or hormonal therapy (aromatase inhibitors [AIs] or tamoxifen), because a greater proportion of LGSOCs express estrogen and progesterone receptors.8 Endocrine therapy is a common treatment of recurrent LGSOC,9 and in retrospective studies, it provided benefit as maintenance therapy in the adjuvant setting.10 Although recurrent LGSOC can follow a chronic, indolent course, it is incurable with current treatments, and patients often die as a result of their disease, highlighting the need for novel therapies.