Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries

Abstract

Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.

International Variation in Female Breast Cancer Incidence and Mortality Rates

“…Previous studies have documented a decline in breast cancer incidence in a several highincome countries related to decreased use of menopausal hormone therapy around the early 2000s (22)(23)(24)(25)(26)(27)(28). In the United States, breast cancer incidence rates dropped nearly 7% between 2002 and 2003, coinciding with the publication of the results of Women's Health Initiative trial on the adverse health effects of menopausal hormone therapy use in postmenopausal women (48).…”

“…Increasing trends in breast cancer incidence in high-income countries over the past several decades are thought to reflect increases in the prevalence of known risk factors (e.g., reproductive patterns and obesity) and increased detection through mammography (20,21). Increases in the use of postmenopausal hormone therapy may have also contributed to the increases in breast cancer incidence rates through the early 2000s (22)(23)(24)(25)(26)(27)(28). Although mammography screening is currently the most effective method for detecting breast cancer at an early stage, it also results in the overdiagnosis of some breast cancers.…”

“…In the United States, breast cancer incidence rates dropped nearly 7% between 2002 and 2003, coinciding with the publication of the results of Women's Health Initiative trial on the adverse health effects of menopausal hormone therapy use in postmenopausal women (48). The continued decline or stabilization in some Western countries has also been attributed to plateaus in participation of mammography screening (20,22).…”

Overdiagnosis in Breast Cancer Chemoprevention Trials

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the reduction in the use of hormone replacement therapy, and the immediacy of the effect suggests the disappearance of established subclinical cancers rather than the prevention of new cancers [23][24][25] . The complementary observations concerning the immediate effects of tamoxifen chemoprevention and hormone replacement withdrawal suggest that a slowly growing er-positive cancer might be induced to regress based on the sudden removal of an estrogenic signal.

We question whether that paradigm is relevant for evaluating antiestrogen-based chemoprevention studies-in particular if the cohorts under study were being followed for incident cancers with annual mammography.

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The influence of pregnancy, parity, and sex on melanoma prognosis

“…However, there is heterogeneity among women within each age group mostly due to the variable use of oestroprogestative contraception or hormone replacement therapy (HRT) in peri-menopause. These treatments have not been consistently used among cohorts making it difficult to broadly conclude on the role of hormones through the study of age categories (119)(120)(121)(122)(123).…”