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More analysis from the Women’s Health Initiative on Hormones and Breast Cancer

16 April 2015 

A study published in JAMA Oncology looks at a new analysis of the longer-term influence of  menopausal hormonal therapy (MHT)  breast cancer risk in two Women’s Health Initiative (WHI) clinical trials. The analysis suggests that over time, a pattern of changing influences can affect breast cancer incidence.

The study examined early and late post-intervention effects on breast cancer involving a total of 16,608 women with an intact  uterus, who received combined hormone therapy and 10,739 women with a prior hysterectomy, who received estrogen only therapy, with a current median follow-up of 13 years,  The study authors stated “The ongoing influences on breast cancer after stopping hormone therapy in the WHI trials require recalibration of breast cancer risk and benefit calculation for both regimens, with greater adverse influence for estrogen and progestin use and somewhat greater benefit for use of estrogen alone” 

 IMS President, Dr Rodney Baber (Sydney, Australia) commented:

This latest report from the Women’s Health Initiative (WHI) investigators provides reassuring news for women using estrogen only Menopausal Hormone Therapy as it shows there is no increased risk of breast cancer even with long term use.  This finding is consistent with the findings of large long term observational studies.

For women using combined MHT the report confirms an overall increased risk of breast cancer that appears at about 5 years of therapy. Previous reports from this group have not found an increased breast cancer risk for women who were using MHT for the first time during the trial. Disappointingly, the information on that group of women is not available in this report.

It is now clear that the risk of breast cancer in women using MHT is quite different for those using estrogen only compared to those using estrogen plus a progestogen (combined MHT).  The risk for women using combined MHT will vary with the type of progestogen, the dose and the duration of therapy. It appears that progesterone and possibly progestogens with chemical structures very similar to progesterone offer greater breast (and cardiovascular) benefits than is the case with medroxyprogesterone as used in the WHI study.

MHT options now available to women are much safer than those used during WHI and it is time for us to move on.

Summary of findings: 

  • An increased risk of BRCA with CEE / MPA in WHI is confirmed but is not statistically significant until the end of the intervention stage.
  • For women who had not previously used HRT breast cancer risk was not increased  for users of CEE /MPA during the intervention stage of the trial.
  • For women using CEE / MPA  there was no significant increase in risk of breast cancer during the post intervention stage.
  • For women using estrogen alone there is no increased risk of BRCA during the intervention stage of  the trial.
  • For women using estrogen  there was a reduction in the risk of breast cancer during the early post intervention stage.  This did not persist during the late post intervention stage but the risk was at no time increased.
  • The postulated mechanisms to explain the effect of CEE are likely correct and the changes in SEER data support that proposition
  • The editorialists have confused the differencebetween progesterone, progestogens and progestins but are correct in postulating that progesterone (sic) is the problem 

The IMS believes that women who start MHT near the time of the menopause need have few worries about safety, and that the benefits of MHT use outweigh any risks. The IMS recommends that any decision to take or not to take HRT should be made according to a woman’s individual circumstances, in consultation with her clinician. 


Joshi PA, Goodwin PJ, Khokha R. Progesterone Exposure and Breast Cancer Risk: Understanding the Biological Roots.JAMA Oncol. Published online April 16, 2015. doi:10.1001/jamaoncol.2015.0512.


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