Breast cancer risk with postmenopausal hormonal treatment

Abstract

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall br...

Breast tumours following combined hormone replacement therapy express favourable prognostic factors

“…This potential explanation is supported by findings showing that the risk of breast cancer decreases as time to last HRT-use increases and seems to vanish after 5 years. 24 In contrast to estrogen-only therapy, combined regimens increase the risk of several types of breast cancer, suggesting that estrogen and progesterone may act synergistically in the promotion and growth of breast tumours. 25 CHRT influenced the risk of breast cancer according to the histological subtype.…”

Use of exogenous hormones and the risk of breast cancer: results from self-reported survey data with validity assessment

“…With respect to use of hormone replacement therapy (HRT), several studies have indicated that HRT use increases the risk of BC. The risk is even higher with longer duration of use and most specifically with the use of estrogen-progestin combination [19][20][21][22].…”

A Principal Stratification Approach to Assess the Differences in Prognosis between Cancers Caused by Hormone Replacement Therapy and by Other Factors

“…An association between HRT and prognosis is likely to be, in part, but not completely, explained by measurable tumor characteristics. Estrogen usage is, for example, associated with the hormone receptor status of primary breast cancer (Collins et al, 2005;Lower et al, 1999) -breast cancers in HRT users are significantly more likely to be estrogen receptor (ER) positive than they are in non-users. Moreover, ER-positive breast cancer is known to have a significantly better prognosis than its ERnegative counterpart (in part due to the fact that ER-positive cancers respond to anti-estrogen therapies).…”