Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

There has been much conflicting evidence out there on risk factors associated with various cancer types that it is sometimes hard to remember what’s important.

A press release from the American Association of Cancer Research (AACR) on menopausal hormone therapy and the risk of developing breast cancer therefore caught my attention with these highlights:

  • Risk varied according to BMI, with greater risks for thinner women.
  • Longer duration of hormone therapy increased breast cancer risk.

The latter was no surprise at all, but seriously, I thought I had read before that a higher not lower BMI was associated with an increased breast cancer risk, but on reflection, that may have been in pre-menopausal not menopausal women.

The authors of this particular research noted that:

“There is substantial epidemiologic, experimental, and clinical evidence that the risk of breast cancer is elevated with the use of menopausal hormone therapy (HT), with formulations containing estrogen and progestin (EPT) resulting in a substantially higher risk than formulations containing estrogen only (ET).”

Despite this evidence, many physicians (PCP’s and gynaecologists) still prescribe different formulations of hormone therapy for treatment of menopausal symptoms:

“It remains unclear whether the number of days per month of progestin use affects risk, specifically whether the continuous-combined EPT regimens (e.g. Prempro) differ from sequential regimens.  Continuous combined HT was associated with the highest risk of hormone-sensitive breast cancer in some, but not all studies.”

Breast cancer is clearly getting increasingly more complex these days with many subsets to consider based on numerous biomarkers and risk factors:

“Some evidence supports a selective increase in risk of particular breast cancer subtypes associated with EPT use, i.e., the estrogen receptor–positive and progesterone receptor–positive subtypes (ER+/PR+).”

This additive effect with EPT can be explained by an increased mitogenic effect of progesterone in the breast tissue.  There is also a need to understand what happens in poor prognosis subsets such as women with triple negative breast cancer (i.e. ER-/PR-/HER2-).

The authors thus reported on the California Teachers Study, a longitudinal epidemiologic trial, which looked at hormone replacement therapy use among 2,857 women for almost 10 years.

Overall, the AACR press release I received summarised the findings nicely:

  1. Breast cancer risk seemed dependent on body mass index (BMI).
  2. Those with a BMI less than 30 appeared to have an increased risk of breast cancer with combined hormone therapy; the risk was strongest among women with BMI less than 25.
  3. In contrast, obese women (i.e. BMI of 30 or more) had no further increase in risk associated with using combined hormone therapy.
  4. The risk of breast cancer was confined to tumors that were positive for both estrogen and progestin receptors. The risk was somewhat weaker for HER2 negative tumors.

Overall, as we have seen with other studies, the research demonstrates that there is a consistent increased risk of breast cancer from hormone therapy use, but it also underscores the need for individual risk-benefit discussions before women begin such therapy, because some subgroups may have different risk profiles.

{UPDATE: the DOI link is not yet working in research blogging so here is the direct link to the abstract and article for now.  Will edit the link later once it has been processed.}


ResearchBlogging.orgSaxena, T, Lee, E, Henderson, KD, Clarke CA,, West, D, Marshall, SF, Deapen, D, Bernstein, L, & Ursin, G (2010). Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study Cancer Epidemiology, Biomarkers & Prevention, 19 (9) :10.1158/1055-9965.EPI-10-0162

2 Responses to “Menopausal hormone therapy and subsequent risk of invasive breast cancer subtypes”

  1. Susanepi

    Thanks so much for posting your blog on this subject (and a link to the reference as I couldn’t find it in online library yet). I have been trying to assess breast cancer risk from non-genetic risk factors and have been struggling with finding a good summary estimate for both HRT exposure and BMI. It will be interesting to see what AACR concludes on this controversial topic as well. My work at the Coriell Institute assesses personalized risk estimtes from both genetic and non-genetic factors for actionable diseases and I am currently working on breast cancer. This is very timely for our research – much appreciated for pointing it out!

  2. MaverickNY

    Thanks for stopping by, Susan. Yes, the lack of link to the journal article in the mainstream media drives me potty too, which is why I always try to provide a direct link or through the Research Blogging widget to help others.
    The paper provides some useful references on the HRT and BMI exposure, which you may find helpful. What was critical in this study was the addition of P, progestins, which are typically synthetic, and appear to carry more risk.
    The link to the California Teachers site in the above post contains a fascinating wealth of info on the thousands of people who participated. I spent an hour looking at the charts and notes there yesterday 🙂
    By the way, later today I’m posting a blog on epigenetics and breast cancer, so that may be useful to you also.

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