Use of hormone therapy and risk of breast cancer detected at screening and between mammographic screens

Abstract

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer, but in women undergoing breast cancer screening it is not clear whether use of HT is associated with increased risk of breast cancer detected at screening or between screens (interval cancer). Further, it is unclear whether the use of the HTs that have been common in Scandinavia is associated with higher risk of breast cancer than the HTs used in other countries. Our study was based on data from 296,651 women aged 50-69 years, who participated in the Norwegian Breast Cancer Screening Program during 1995-2004. After a mean enrollment time of 3.8 years, 1,512 women were diagnosed with invasive screen detected breast cancer, and 814 with invasive interval breast cancer. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer associated with HT use, after adjusting for confounders. Ever users of HT had a 58% increased risk of breast cancer, compared to never users. The HRs associated with HT use were 1.45 (95% confidence interval (CI) = 1.29-1.63) for screen detected and 1.89 (95% CI = 1.61-2.23) for interval cancer. The difference between screen detected and interval cancer was statistically significant (p = 0.011). The HR of breast cancer increased with duration of HT use, but significantly more so for interval than for screen detected cancer (use of HT for 5 or more years compared to never use; HR = 2.91, 95% CI = 2.10-4.04 and HR = 1.94, 95% CI = 1.51-2.50, respectively; p = 0.002). The population attributable fraction of breast cancer due to HT use was 19.8% overall. Ever users of HT tended to develop a cancer of lower grade. No other differences in histological tumor characteristics were observed between ever and never users of HT among screen detected or interval cancers. The estimated risks of either breast cancer overall with HT use are higher in Norway than reported in similar studies from the U.S. HT-use is a stronger risk factor for interval cancer than for screen detected cancer. The increased risk of interval cancer, which may partly be due to decreased sensitivity of mammograms in HT users, remains a challenge in breast cancer screening programs.