Combined hormone therapy increases lobular breast cancer risk

Combined estrogen and progestagen postmenopausal hormone therapy preferentially increases the risk for estrogen receptor (ER)-positive, lobular breast cancer, study findings indicate.The study also showed that progesterone and dydrogesterone seem to have a more favorable risk profile than other progestagens, a finding which could have "major public health implications," say Françoise Clavel-Chapelon (Institut Gustave Roussy, Villejuif Cedex, France) and colleagues.The results of many epidemiological studies suggest that combined postmenopausal hormone therapy increases the risk for breast cancer.However, breast cancer is not a single entity, and tumors with different histologic or hormone receptor profiles are etiologically distinct, observe the researchers.Also, combined hormone therapy varies in dose, routes of administration, and regimens and may, therefore, differentially affect breast cancer risk."Knowing how different hormone therapies affect the risk of different types of breast cancer would provide a useful insight into the mechanisms by which hormone therapies act in the carcinogenic process," Clavel-Chapelon et al comment in the Journal of Clinical Oncology.The researchers analyzed data on 80,391 postmenopausal women aged a median of 53 years who were interviewed and monitored between 1990 and 2002.Information on lifetime use of hormonal treatments including start date, brands, and duration of each episode was requested.Hormone therapies were subsequently classified as estrogen plus progesterone, estrogen plus dydrogesterone, or estrogen plus other progestagens.Overall 70% of women in the cohort had ever used hormone therapy, while the remaining 30% were never users.After an average of 8.1 years of follow up, 2355 women developed primary invasive breast cancer.Use of estrogen plus progesterone therapy did not significantly increase the risk for breast cancer as a single entity compared with never use.However, women who used estrogen plus progesterone had a 1.7-fold increased risk for lobular and ER-positive/progesterone receptor (PR)-negative breast cancer compared with never users.Notably, women who used estrogen plus other progestagens faced an increased risk for ductal (1.6-fold) and lobular (2.0-fold) carcinomas as well as ER-positive/PR-positive (1.8-fold) and ER-positive/PR-negative carcinomas (2.6-fold).Progestagens are thought to act on breast tissue through their interactions with steroid receptors, growth factors, and oncogenes, and with the cell-cycle and estrogen-metabolizing enzymes, Clavel-Chapelon et al note.Because progestagens differ in their chemical structure, metabolism, pharmacokinetics, and potency, it is reasonable to expect them to induce different responses in the breast, they speculate.Clavel-Chapelon and colleagues conclude: "Further research is needed on combined hormone therapies containing progesterone or dydrogesterone, which might be less harmful regarding breast cancer risk than those containing other progestagens."