Hormone Therapy

Menopausal Hormone Therapy and Underlying Breast Cancer Risk

The 2015 Endocrine Society guideline for the treatment of menopausal symptoms provided recommendations regarding the use of menopausal hormone therapy among women with different degrees of breast cancer risk.1 However, the guideline did not provide instructions on how to calculate actual risk of patients on an individual level.

Recently, the Journal of Clinical Endocrinology and Metabolism published a paper on consideration of underlying breast cancer risk and its effect on actual breast cancer risk among women interested in receiving menopausal hormone therapy.2 Consultant360 discussed this work further with lead author Richard J. Santen, MD, professor of medicine in the Division of Endocrinology and Metabolism at the University of Virginia, and former president of the Endocrine Society.

Consultant360: What misconceptions are common among patients regarding excess risk of breast cancer associated with menopausal hormone therapy?

Richard Santen: When the lay press disseminates information about the risk of breast cancer associated with menopausal hormone therapy, it often overestimates this risk in many patients. Among women whose underlying risk of breast cancer is low, their excess risk of breast cancer from menopausal hormone therapy is also low. Many patients become concerned when they hear of the risk of breast cancer associated with menopausal hormone therapy among women with average risk of breast cancer, but this category really does not apply to patients who are at low risk of breast cancer, which approximates 70% of the population.

CON360: Could you discuss the importance of your paper when it comes to proper risk stratification for breast cancer among women with menopause who are interested in taking hormone therapy?

RS: When most publications publish information about the risk of breast cancer associated with hormonal therapy, the authors of these publications take the average risk and do not consider the underlying risk. In the past, many publications have never emphasized the need to determine underlying risk in calculating actual risk individually for each patient. This is an important issue. If a patient has a very low underlying risk of breast cancer, the increased or excess risk due to menopausal hormone therapy is very low. On the other hand, if a patient has a high underlying risk of breast cancer, the excess risk due to hormonal therapy can be high.

CON360: How might the findings from your analysis inform future guidelines, especially since recent guidelines such as those from the Endocrine Society did not calculate the magnitude of the effect of underlying or attributable risk of breast cancer on actual risk?

RS: My colleagues and I wrote the most recent Endocrine Society guidelines for the treatment of the symptoms of menopause. In those guidelines, we recommended not prescribing hormone therapy to people with high risk of breast cancer, exercising caution in prescribing hormone therapy to women with intermediate risk, and that it is safe to prescribe hormone therapy to women with low risk.1 However, in those guidelines, we did not calculate or explain how physicians can calculate this risk.

Going forward, I think future guidelines should actually instruct physicians on how to calculate each patient’s individual risk by taking into account their underlying risk in combination with the excess risk from menopausal hormone therapy. Even though this concept may seem very simple, it has not been done previously. This change in the guidelines may not happen because most guidelines issued by other organizations have not cautioned physicians to take into account the underlying risk in each patient, but instead to use the average risk alone.

CON360: What clinical takeaway do you hope to leave with endocrinologists, obstetrician-gynecologists, and related practitioners through this work?

RS: The major message from this manuscript is that physicians should find out what the underlying risk is for breast cancer when considering hormonal therapy in each individual patient, and then multiply that underlying risk by the excess risk associated with hormonal therapy. If a woman is at low risk of breast cancer, she has a very small excess risk of breast cancer if she takes menopausal hormone therapy. Physicians can reassure patients with low underlying risk of breast cancer that menopausal hormone therapy is safe for them.

CON360: What is the next step in terms of future research in this area?

RS: The next step in future research would be to prospectively look at subgroups of women at low, intermediate, and high risk of breast cancer with and without hormone therapy, and to determine prospectively whether this excess risk calculation is valid using that methodology. Current methodology is retrospective, but we need prospective data on this.



  1. Santen RJ, Heitjan DF, Gompel A, et al. Underlying breast cancer risk and menopausal hormone therapy [Published online February 13, 2020]. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa073
  2. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011. https://doi.org/10.1210/jc.2015-2236