Breast cancer risk factors by mode of detection among screened women in the Cancer Prevention Study-II

Background: Identifying risk factors for women at high risk of symptom-detected breast cancers that were missed by screening would enable targeting of enhanced screening regimens. To this end, we examined associations of breast cancer risk factors by mode of detection in screened women from the Cancer Prevention Study (CPS)-II Nutrition Cohort. Methods: Among 77,206 women followed for a median of 14.8 years, 2711 screen-detected and 1281 symptom-detected breast cancer cases were diagnosed. Multivariable-adjusted associations were estimated using joint Cox proportional hazards regression models with person-time calculated contingent on screening. Results: Factors associated with higher risks of symptom-detected and screen-detected breast cancer included current combined hormone therapy (HT) use (HR 2.07, 95% CI 1.72–2.48 and 1.45, 1.27–1.65, respectively) and history of benign breast disease (1.85, 1.64–2.08 and 1.43, 1.31–1.55, respectively). Current estrogen-only HT use was associated with symptom-detected (1.40, 1.15–1.71) but not screen-detected (0.95, 0.83–1.09) breast cancer. Higher risk of screen-detected but not symptom-detected breast cancer was observed for obese vs. normal body mass index (1.22, 1.01–1.48 and 0.76, 0.56–1.01, respectively), per 3 h/day sitting time (1.10, 1.04–1.16 and 0.97, 0.89–1.06, respectively), and ≥ 2 drinks per day vs. nondrinker (1.40, 1.16–1.69 and 1.27, 0.97–1.66, respectively). Conclusions: Differences in risk factors for symptom-detected vs. screen-detected breast cancer were observed and most notably, use of combined and estrogen-only HT and a history of benign breast disease were associated with increased risk of symptomatic detected breast cancer. Impact: If confirmed, these data suggest that such women may benefit from more intensive screening to facilitate early detection.