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. ©2016 American Association for Cancer Research.