Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14–1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11–1.65), 1.26 (95% CI: 1.00–1.60), and 1.40 (95% CI: 1.01–1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04–2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78–2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13–1.53) (p_interaction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.     

Effects of Variant Histology on the Oncologic Outcomes of Patients With Upper Urinary Tract Carcinoma After Radical Nephroureterectomy: A Propensity Score–Matched Analysis

PurposeTo determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU).Patients and MethodsThe data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes.ResultsUTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P = .011, P = .002, P = .006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR) = 1.92; 95% confidence interval (CI), 1.27-2.89; P = .002], CSS (HR = 4.47; 95% CI, 1.99-10.1; P = .001), and OS (HR = 3.00; 95% CI, 1.55-5.78; P = .001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P = .562, P = .060, P = .153, respectively).ConclusionUTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients.