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

Abstract

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 5 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.Key words: breast cancer; histological type; hormone therapy; progestin; epidemiology Menopausal hormone therapy (HT) has been established as a risk factor for the development of breast cancer, 1 with combined estrogen-progestagen (EP) therapy posing a greater risk than mono-estrogen therapy.2-7 The extent to which this risk difference is in turn affected by duration and recency of use, particularly for past long-term users, requires further clarification. Recent evidence from observational studies has shown that risk varies according to tumor histology, with current use of both mono-estrogen and EP therapy carrying greater risks for invasive lobular and tubular cancers than for invasive ductal cancer. 4,[8][9][10][11][12][13][14][15][16] The higher risk associated with EP therapy compared to mono-estrogen therapy has also been observed across different histological tumor types. 6,17,18 Several studies have investigated differences in risk by regimen, 2,5,18-21 however, a higher risk for continuous than for cyclical EP therapy was found only in Scandinavian studies. 18,20,22 Less information is available on the role of progestagens in EP therapy, specifically regarding the effects of type, dose and the number of days it is administered each month. Wh...

Androgen in postmenopausal women

“…Estrogen has favorable effects on insulin sensitivity, blood pressure and lipid metabolism, but androgenic activities of progestogens have unfavorable effects on these favorable effects of estrogen. In particular, testosterone-derived progestogens, such as levonorgestrel and norethisterone, have been reported to be associated with increase in the risk of breast cancer (82). Therefore, it is necessary to pay attention to lipid metabolism, insulin sensitivity and risk of breast cancer when using a testosterone-derived progestogen.…”

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

“…More detailed information on the study population can be found elsewhere. 24 Face-to-face interviews were carried out by trained interviewers using a standardized questionnaire to collect information on sociodemographic characteristics as well as putative risk factors for breast cancer, including reproductive history, use of hormone replacement therapy (HRT), family history of breast cancer, physical activity, smoking and alcohol consumption.…”

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

“…1 However, we are concerned by several shortcomings of this study. We cannot find an explanation or hypothesis, respectively, why 44.0% of randomly selected controls did not participate and a further 12.6% controls did not respond.…”

“…2,3 It is difficult to understand the nature of both varying and steadily decreasing absolute numbers of study women used for analyses. For example, overall there were 3,464 eligible cases for analyses (Table I) 1 , but how does this correspond to the sum of 4,359 cases (in situ disease excluded) in Figure 1 1 , reflecting absolute and relative numbers of study women with reported ever, current and past use, respectively? Likewise, the numbers of controls do not match.…”

“…Given the fact that substantial numbers of German women start MHT already before the age of 50 [6][7][8] and that hysterectomy rates were calculated to be 25% in women aged 40-69 years in West German, 7 one would have liked to see more details on risk of breast cancer in these subgroups of women in the two study regions. 1 …”