e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.
Neuropilin1, a novel independent prognostic factor and therapeutic target in triple-negative breast cancer
