What is the role of HRT in the incidence of breast cancer in the US?

Updated: Feb 04, 2021
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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The reason for the decline has been extensively debated. Breast cancer rates decreased significantly after the reports from the Million Women Study [72] and the Women’s Health Initiative showing higher numbers of breast cancers in women using combination HRT with estrogen and progestin for menopausal symptoms. The near-immediate decrease in the use of combination HRT for that purpose has been widely accepted as a primary explanation for the decrease in breast cancer rates. [70]

However, Jemal and Li argued that the decline in breast cancer incidence started earlier than the reduction in combination HRT use and that the decline is due in part to a “saturation” in mammographic screening mammography that produced a plateau in incidence when such screening stabilized in the late 1990s. [66, 69] Saturation of the population would be predicted to reduce the pool of undiagnosed or prevalent cases.

For women aged 69 years or older, breast cancer rates started to decline as early as 1998, when screening first showed a plateau. This observation is consistent with the prediction that if widespread screening and earlier detection are effective, they should result in a peak incidence among women during the sixth and seventh decades of life, followed by a decline. This is exactly the pattern now being reported for screened populations. [73]

The second observation noted by Jemal et al was that despite evidence for a plateau effect, screening saturation alone could not explain the dramatic declines or the pattern of decline. The decline in incidence was observed only for ER-positive tumors and not for ER-negative ones; these findings support the competing hypothesis that exposure to HRT as estrogen in combination with synthetic progesterone promoted the growth of undetected tumors.

Under this scenario, withdrawal of combination HRT at the population level may have resulted in regression or a slowing of tumor growth. The latter, it has been argued, would result in a delay in detection. Overall, incidence figures from 2005-2009, for which the most recent data are currently available, suggest that overall new breast cancer case rates have remained fairly stable since the initial drop.

It is notable, however, that the annual percentage change from 2005 to 2009 increased in women aged 65-74 years by 2.7% during this period, rates that parallel 2001 incidence figures for this age group. [6] This rise occurred in spite of very low use of HRT by this population [74] and suggests that the drop in combination HRT use immediately after 2002 may not have resulted in a sustained decrease in new breast cancer cases.

At present, it is unclear whether decreased use of combination HRT has resulted in a sustained reduction in the incidence of breast cancer at the population level or has shifted the age at which preexisting disease would become detectable. Longer-term follow-up of post-2002 trends in relation to combination HRT use are needed to address this question.

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