Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy

• Published in: International journal of cancer Vol. 123; no. 4; pp. 933 - 941
• Main Authors: Flesch‐Janys, Dieter, Slanger, Tracy, Mutschelknauss, Elke, Kropp, Silke, Obi, Nadia, Vettorazzi, Eik, Braendle, Wilhelm, Bastert, Gunter, Hentschel, Stefan, Berger, Jürgen, Chang‐Claude, Jenny
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2008; Wiley-Liss
• Subjects: Biological and medical sciences; breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - pathology; Case-Control Studies; epidemiology; Estrogen Replacement Therapy; Female; Germany - epidemiology; Gynecology. Andrology. Obstetrics; histological type; hormone therapy; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Postmenopause; progestin; Tumors; Germany; Breast disease; progestin; Hormone therapy; Breast cancer; Malignant tumor; Epidemiology; Ovarian hormone; Progestagen; Mammary gland diseases; Cancerology; Risk factor; Histological type; Postmenopause; Progesterone; Sex steroid hormone; Therapeutic protocol; Cancer
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.23655

In a large population‐based case–control study in Germany, including 3,464 breast cancer cases aged 50–74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face‐to‐face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%‐confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55–1.94) and heterogeneous by histological type (p < 0.01), being more than 2‐fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04–1.06) for continuous combined estrogen–progestagen, 1.03 (95% CI, 1.02–1.04) for cyclical EP and 1.01 (95% CI, 1.00–1.03) for estrogen‐only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone‐ or levonorgestrel‐derived progestagens than for continuously administered progesterone‐derived progestagens (OR, 2.27, 95% CI, 1.98–2.62 vs. 1.47, 95% CI, 1.12–1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose. © 2008 Wiley‐Liss, Inc.