What is the correlation between trends in breast cancer incidence and postmenopausal hormone use?

Updated: Dec 26, 2019
  • Author: Graham A Colditz, MD, DrPH; Chief Editor: Chandandeep Nagi, MD  more...
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Numerous studies in the United States and internationally have reported on the decline in breast cancer incidence after 2002. [50] Based on data from the San Francisco mammography registry, prescribing of estrogen and progestin peaked in 1999. Before publication of the Heart and Estrogen/Progestin Replacement Study (HERS), the use of hormone therapy was increasing at 1% per quarter but declined by 1% per quarter after the publication. This decline in prescribing continued until the publication of the WHI in 2002, at which point a more substantial decline of 18% per quarter was observed. The peak and decline through 1999 to 2002 is concordant with the HERS report in 1998 showing a significant increase in coronary heart disease (CHD) in the first year of therapy among women with prevalent coronary disease, as well as no long-term benefit in reducing CHD.

The growing epidemiologic evidence published since 2000 on the adverse effects of combination therapy on breast cancer added further evidence against the use of this therapy. Based on the prevalence of use of estrogen and progestin in California, Clarke et al estimate a population attributable risk (PAR, or the proportion of cases caused by estrogen and progestin) of up to 11% based on a prevalence of use of 30% and a RR of 1.4. [51] Given that substantially higher RRs of 2 or more have been reported, this estimate of the PAR is conservative. Assuming a prevalence of use of 17.5%, the average reported for California in 2001, a RR of 1.49 gives a PAR of 7.9%, and a RR of 2.0 gives a PAR of 14.9%.

Evidence for breast cancer incidence rates now clearly shows a parallel drop in breast cancer consistent with the pattern of decreased prescribing. The rigorous, state-of-the-art analysis using joint point analysis and drawing on SEER incidence data from 1975-2003 shows a significant decrease in the incidence of invasive breast cancer from 1999-2003 in all 5-year age groups from 45 years and older and a sharp decrease largely limited to ER-positive tumors in those aged 50-69 years between 2002 and 2003. If screening were to account for a drop in incidence, rates of in situ disease would also need to drop, as they are detected almost only with mammography.

Follow-up of women in routine screening shows a similar drop in incidence, further ruling out changes in screening patters as the explanation. Data from the WHI add further support to this decrease in risk after cessation and the late promoter effect of combination therapy. [52]

Others have analyzed SEER data over a shorter period or draw on the unique resources of the California tumor registry and the HMO datasets [12] to show similar relationships between change in hormone therapy and a decrease in breast cancer incidence. Most recently, Robbins and Clarke evaluated the change in prescribing as estimated from the California Health Interview Survey (CHIS) for almost 3 million non-Hispanic white women aged 45-74 years against the change in breast cancer incidence across 58 counties in California. This thoughtful analysis shows that, from 2001-2004, incidence declined by 8.8% in the counties with the smallest estrogen and progestin reductions, by 13.9% in those with intermediate reductions, and by 22.6% in counties with the largest reductions in combination postmenopausal hormone therapy. [53]

Between 2001 and 2003, CHIS data did not show any significant change in the proportion of women who reported having a mammogram in the previous 2 years, adding further evidence against this as a plausible major explanatory factor in the observed declines in incidence. Even more evidence in support of this relationship between decrease in estrogen and progestin and breast cancer comes from declines in incidence that parallel those in the United States as reported in New Zealand and Germany. Based on these data and the IARC classification of estrogen plus progestin as a carcinogen, it can be concluded that removal of estrogen plus progestin acting as a promoter accounts for this rapid drop in incidence.

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