What is the relationship between Hormone Replacement Therapy (HRT) and the risk of developing breast cancer?

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From the Guidelines

Hormone replacement therapy (HRT) is associated with a modest increase in the risk of breast cancer, with 8 more invasive breast cancers expected per 10,000 women taking estrogen and progestin for 1 year. The level of risk varies based on the type of HRT and duration of use, as noted in a study published in the Annals of Internal Medicine 1. Key factors to consider include:

  • The type of HRT: Combined HRT (estrogen plus progestin) carries a higher risk than estrogen-only therapy
  • Duration of use: The risk increases with longer duration of use, becoming more significant after 1 year of treatment, as reported in the study 1
  • Individual risk factors: Women with a personal or strong family history of breast cancer, or known genetic mutations, should generally avoid HRT or consider non-hormonal alternatives The increased risk occurs because estrogen and progestin can stimulate growth of hormone-sensitive breast tissue and potentially promote development of hormone-dependent breast cancers. Women considering HRT should use the lowest effective dose for the shortest time needed to manage menopausal symptoms, as recommended by the USPSTF 1. Each woman should discuss her individual risk factors with her healthcare provider to make an informed decision about whether the benefits of HRT for managing menopausal symptoms outweigh the potential breast cancer risk in her specific situation.

From the Research

Hormone Replacement Therapy and Breast Cancer Risk

  • The relationship between hormone replacement therapy (HRT) and breast cancer risk is complex and has been studied extensively 2, 3, 4, 5, 6.
  • Observational studies suggest that long-term HRT may increase breast cancer development, while estrogen reduction (oophorectomy) significantly reduces recurrence in premenopausal women 2.
  • The influence of HRT on the growth of established breast cancer has not been determined, but current evidence cannot exclude a risk that HRT increases recurrence to the same degree 2.
  • Some studies have found that certain synthetic progestogens, but not progesterone and dydrogesterone, can accelerate the proliferation of breast cancer cells in vitro and in animal studies 4.

Types of Hormone Replacement Therapy and Breast Cancer Risk

  • Conjugated equine estrogen and medroxyprogesterone acetate are associated with decreased risk of breast cancer relative to bioidentical hormone therapy and controls 5.
  • Bioidentical estrogen and progesterone are supplements whose molecular structures are identical to what is made in the human body, but no peer-reviewed articles support their benefits over synthetic supplements 5.
  • A nationwide population-based cohort study found that menopausal hormone therapy (MHT) was associated with an increased risk of breast cancer, but not all MHTs increased the risk 6.
  • Specific combined therapies, such as EH/DRSP, EH/DYD, EH/NETA, and EV/CPA, were associated with higher risk, whereas estrogen alone and tibolone were not 6.

Considerations for Hormone Replacement Therapy in Breast Cancer Survivors

  • Breast cancer survivors should be offered HRT only with caution and with their full participation in the decision-making process 2.
  • Climacteric symptoms in breast cancer survivors should be delineated for type and severity for methodical management, and lifestyle modifications can be effective for mild symptoms 3.
  • Non-hormonal pharmaceutical approaches can be used as second-line therapy for control of hot flashes, vulvo-vaginal atrophy, arthralgia, mood swings, sleep disturbance, and depression 3.
  • Informed consent and shared-decision-making is a reasonable approach for HRT use in symptomatic breast cancer survivors 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Elements of informed consent for hormone replacement therapy in patients with diagnosed breast cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 1999

Research

Hormone replacement therapy after breast cancer: Yes, No or maybe?

Molecular and cellular endocrinology, 2021

Research

The choice of progestogen for HRT in menopausal women: breast cancer risk is a major issue.

Hormone molecular biology and clinical investigation, 2018

Research

Relationship between menopausal hormone therapy and breast cancer: A nationwide population-based cohort study.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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