Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women

Abstract

REAST CANCER IS THE MOST common invasive cancer in US women and its etiology is not fully defined. 1,2 Despite observational studies suggesting increased breast cancer risk with estrogen 3 and especially long-duration combined hormone use, 4,5 the magnitude of breast cancer risk associated with menopausal hormone therapy is controversial. 6,7 On July 9, 2002, the Women's Health Initiative (WHI) reported results from the randomized controlled trial of 16 608 postmenopausal women comparing effects of estrogen plus progestin with placebo on chronic disease risk and confirmed that combined estro

Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors

“…9 The Women's Health Initiative Study firmly established that treatment with progestin in combination with estrogen (E2) for attenuating postmenopausal symptoms increases the risk of breast cancer, particularly TNBC. 10 This finding is corroborated to some extent in mice, in which progesterone (P4) promotes 7,12-dimethylbenz[a]anthracene-induced mammary tumors. 11,12 Breast cancer cells and tumors respond to progestins through an unknown mechanism, which generally act as pro-survival and proliferative factors.…”

Is HRT still indicated for the primary prevention of osteoporosis?

“…by EMEA in December 2003, is largely the consequence of the believe that HRT should increase the risk of breast cancer, mainly deduced again from the first publications of the WHI data [26,27]. However, newer publications from the WHI are showing a quite different picture.…”

Hormone replacement therapy and female malignancy: what has the Million Women Study added to our knowledge?

“…Level I evidence) suggests the MWS probably overestimated the degree of risk attributable to HRT and underestimated the duration of exposure associated with an increase in incidence. [13][14][15] The latter is accounted for in that risk estimates were based on information about duration of HRT use at recruitment only. Adding an average of 1.2 years (i.e.…”

“…This evidence has shown that it is probably only combined therapy that results in an increase in mammographic breast density and hence a potential impact on interval cancer rates due to a reduction in sensitivity (increasing the chance of a cancer being missed at a previous screen). 13,15,21 Only about 25% of women who use combined therapy actually develop any density increase and when it occurs it is of the order of about a 5% increase. 21 This effect of combined HRT occurs regardless of the class of progestogen or prescription pattern (i.e.…”

“…5 years) if allocated to receive combined therapy, compared with those allocated to receive placebo. 13,22 However, the WHI study reported that density change with combined therapy was not predictive of an abnormal mammogram. 22 Whilst an increased breast density could lead to an increase in interval cancers due to 'missed' abnormalities at screening, there are no data from randomised trials to provide more reliable estimates of interval cancer rates and the prognostic features of screen-detected versus interval cancers to determine whether this has any impact on breast cancer mortality.…”