Cancer Therapies

Hormone replacement therapy and breast cancer

Hormone replacement therapy (HRT) are  agents derived from outside of the body or artificial hormones that replace natural hormones that are reduced  in menopausal women. The two main artificial  hormones are:

  • Estrogen include estradiol, estrone and estriol
  • Progestin, a synthetic version of the hormone progesterone such as dydrogesterone, medroxyprogesterone, norethisterone, and levonorgesterol

These hormones can be used together (combined HRT) or taken as estrogen alone (estrogen alone HRT).

HRT was widely used as an effective treatment for reducing the symptoms of menopause such as hot flushes, sleeping disturbance, depressive mood, muscle, and joint pain. In addition, the combined HRT was found to reduce the risk of cancer of the uterus. 

The biological mechanisms underlying the effect of synthetic hormones on the breast are complex. Breast cancer is strongly influenced by hormonal factors.

It is thought  that progesterone of the combined HRT regimen may increase new cell formation  and thereby lead to the DNA or genetic damage.

The combined estrogen plus progestin HRT is now an established risk factor for breast cancer. In 2002, the Women’s Health Initiative randomized clinical trial was terminated early owing to findings of an increase in breast cancer incidence and cardiovascular disease among postmenopausal women using the combined regimen.

The same conclusions were found soon after in the observational Million Women’s Study from the United Kingdom.  Breast cancer incidence decline and decreased HRT utilization has shown a high correlation; the decline of breast cancer incidence was found to begin about two years after the HRT decline.

A recently published (2019) important study by the Collaborative Group on Hormonal Factors in Breast Cancer reported that for women of average weight in developed countries, 5 years of menopausal HRT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about:

  • one in every 50 users of estrogen plus daily progestin preparations
  • one in every 70 users of estrogen plus intermittent progestin preparations
  • one in every 200 users of estrogen-only preparations

Increased risk of breast cancer has been positively associated with

  • Length of exposure, time since menopause, and for estrogen receptor (ER)-positive disease
  • Greatest risk for hormonally responsive lobular, mixed ductal-lobular, and tubular cancers
  • Very dense breasts, while no excess risk was found in women with fatty breasts
  • Family history of breast cancer was not associated with a significantly increased incidence of breast cancer but was associated with a significantly reduced total mortality rate

Estrogen alone HRT is advised in women who have already undergone a hysterectomy. Estrogen-only therapy for 5-9 years in women with hysterectomy was found to be associated with a significant 23% reduction in the annual incidence of invasive breast cancer.

Use of any HRT following ovarian removal  was also not associated with an increased risk of developing breast cancer, and interestingly, a possible protective effect was found for such women who used estrogen-containing HRT alone.

Furthermore, HRT benefits young women at menopause and outweigh any small risks associated with HRT. Because of the association between breast cancer and HRT, only the minimal duration of HRT use is recommended for symptom control, and it is not recommended for chronic disease management.

It is recommended that a person should not be a smoker, should have annual mammograms and have cardiac checkup before consulting a gynaecologist for hormone replacement therapy.

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