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Postmenopausal Hormone Therapy and Breast Cancer Prognostic Characteristics: A Linkage between Nationwide Registries

Background: The effects of use of different types of hormone therapy on breast cancer risk according to prognostic factors are largely unknown. Methods: We linked data from the Norwegian Prescription Database and the Cancer Registry of Norway during 2004 to 2009 on all women ages 45 to 79 years (N = 686,614). We estimated rate ratios and 95% confidence intervals for breast cancer in relation to hormone therapy using Poisson regression. Results: During an average 4.8 years of follow-up, 7,910 invasive breast cancers were diagnosed. Compared with nonusers of hormone therapy, users of estradiol and tibolone were more likely to be diagnosed with grade I, lymph node–negative, and estrogen receptor–positive (ER+)/progesterone receptor–positive (PR+) tumors. However, compared with nonusers, users of the most common estrogen and progestin combinations [estradiol–norethisterone acetate (NETA) preparations (Kliogest, Activelle or Trisekvens)] were at a 4- to 5-fold elevated risk of grade I tumors, 3-fold elevated risk of lymph node–negative tumors, and 3- to 4-fold elevated risk of ER+/PR+ tumors. Importantly, estradiol–NETA users were also at a 2- to 3-fold increased risk of medium differentiated (grade II) tumors and tumors with lymph node involvement. Conclusions: Use of oral estradiol, tibolone, and estradiol–NETA predominantly increases the risk of breast cancer with favorable prognosis characteristics. However, use of estradiol–NETA preparations also increases the risk of breast cancers with less favorable characteristics. Impact: The hormone therapy preparations most commonly used in the Nordic countries are associated with both breast cancers with good and less favorable prognosis characteristics. Cancer Epidemiol Biomarkers Prev; 25(11); 1464–73. ©2016 AACR.