Hormone-Replacement Therapy and Its Association with Breast Cancer Subtypes: A Large Retrospective Cohort Study

Abstract

Purpose: The study examined trends in breast cancer incidence, mammography testing rates, hormone-replacement therapy (HRT) use and breast cancer subtypes in a large Israeli health maintenance organization during 2000-2014.

Methods: Annual rates of mammography tests and HRTs use were analyzed in women age ≥45. Annual incidence rates of breast cancer were analyzed in women age ≥20. Estimated annual percentage changes were used to test changes in incidence rates. Invasive breast cancer subtypes were approximated by treatments received. We compared annual rates and duration of HRTs use between women diagnosed with breast cancer and those who were not, as well as HRT use between subtypes of invasive breast cancer.

Results: We identified 14,092 breast cancer cases (88% invasive, 12% in situ). The age-adjusted incidence rate of invasive breast cancer peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use decreased from 13.2% in 2002 to 4.6% in 2014. The subtypes distribution of 7771 patients diagnosed with invasive breast cancer during 2007-2014 was: luminal A and B without HER2 over-expression (HR+/HER2-), 69.7%; Luminal B with HER2 over-expression (HR+/HER2+), 8.9%; Hormone receptor-negative HER2 enriched (HR-/HER2+), 5.4%; triple negative (HR-/HER2-), 10.0%; unknown, 6.0%. Overall, in women age ≥45 diagnosed with invasive breast cancer, 76-86% did not have HRT exposure vs 14-24% who were current (within 1 year before the breast cancer diagnosis), recent (within 2-5 years), or past users (>5 years). Current/recent HRT use was statistically significantly higher in luminal vs non-luminal/unknown breast cancer subtypes (13.9% vs 8.9%, respectively; p < 0.001).

Conclusion: Our results show a decrease in breast cancer incidence that parallels the global and local decrease in HRT use. Yet, our results imply that current/recent HRT exposure may contribute to the incidence of luminal breast cancer tumors in particular. The magnitude of the effect supports findings from population-based studies.

Keywords: breast cancer; epidemiology; hormone-replacement therapy; incidence; mammography.

Figure 1

Study population included in each of the analyses of the study.

Figure 2

Breast cancer incidence 2002–2014. (A) Age-adjusted annual incidence rate of breast cancer by type and overall. (B) Age-specific annual incidence rates of breast cancer overall (invasive and in situ).

Figure 3

Annual proportions of HRT use 2002–2014 among all female MHS members (age ≥ 45 years) by period of use (current users, HRT use in the calendar year/year prior to breast cancer diagnosis; recent users, HRT use in any of the years 2–5 before each calendar year/year of breast cancer diagnosis).

Figure 4

Annual proportions of current use of HRT according to breast cancer status (age ≥ 45 years). Differences in HRT use between breast cancer free women and those diagnosed with any breast cancer were statistically significant (p < 0.05) in 2003 and 2007–2014.

Figure 5

Invasive breast cancer classification and HRT use during 2007–2014 among MHS female members age≥45 years on diagnosis (n =6218). The analysis includes current users (within 1 year prior to the breast cancer diagnosis), recent users (within 2–5 years), past users (>5 years), and non-users.