Although it is agreed that long-term HT slightly increases the risk of breast cancer, the definition of long-term risk is still unclear, particularly in view of data showing that it may vary significantly by type of HT (estrogen alone vs estrogen-progestin, brand of progestin, dosage).The Kaiser Permanente health plan questions whether trends in breast cancer incidence and use of HT over the past 25 years may be directly linked.

The Women’s Health Initiative (WHI) trial provided information based on the best available study methodology. By adopting its results as the ultimate source of information, many organizations, medical societies and health authorities actually declared that data derived from observations in the postmenopausal population are less valuable. Nevertheless, recently, several studies have used databases on the incidence of breast cancer, on the one hand, and sales of HRT on the other hand, in order to suggest a direct link between trends of hormone use and the number of newly diagnosed breast cancer patients. Such information is very important and interesting, but conclusions must be drawn with great caution. It is tempting to simplify the observed year-by-year figures on HT use and breast cancer incidence and establish a “mirror glass” equation: the more postmenopausal hormone use, the more breast cancer, and vice-versa. This mechanistic approach is too simplistic.

A third important player, i.e. the rate of mammography screening, has been proved to have similar fluctuations as HT use and breast cancer incidence. In the Kaiser Permanente registry, the rate of women aged 45-59 undergoing screening mammography in 2002-2004 (post WHI period) decreased from 48% to 44%. Thus, awareness of the need for periodic breast examinations may ease, and the likelihood of women coming to be examined may decrease in a population that uses HT less frequently, which could lead to under-diagnosis of breast cancer.

The 28% increase in breast cancer incidence between the early 1980s and the early 1990s observed in the Kaiser Permanente cohort probably reflects the outcome of implementation of the mammography screening program during that period.

The largest group among HT users in most countries (excluding USA) has always been women younger than 60 years. The Kaiser Permanente data show that, for women aged 45-59, the 70% drop in HT use in year 2006 was associated with a non-significant decrease of 4.9% in breast cancer incidence, which translates into a reduction of less than one case of breast cancer per 10,000 women per year. Furthermore, in younger women (age groups <45 years and 45-59 years ), the incidence of invasive breast cancer started to decrease before the year 2000.This is similar for the incidence of localized cancers, and the age-adjusted annual incidence rate of both estrogen receptor-positive and receptor-negative breast cancers. Therefore, the decrease of breast cancer incidence analysed from different angles cannot be attributed simply to the drop in HT use, which started after the publication of the WHI study. There must be another, non-hormonal and still yet unknown factor explaining, at least in part, these changes in incidence since 1998.

The new epidemiological data coming from the Kaiser Permanente study do have scientific merits, but may be confusing when interpreted for the lay public. Health-care providers should stay with the first-grade information coming from the WHI study when discussing this issue with their patients: breast wise, in women younger than 60, HT (particularly estrogen alone) is safe. Long-term use may be associated with a small increased risk, in the order of one extra case per 1000 women per year. Weighing the overall benefits and risks of HT in younger postmenopausal women clearly favours the use of HT for symptomatic women.

Public release date: 24 July 2007 International Menopause Society