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Relationship Between Long Durations and Different Regimens of Hormone Therapy, Menopause, and Risk of Breast Cancer

Review on November 24, 2009

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More and more observational studies, combined with information from the Women's Health Initiative (WHI) show that after menopause, women using combined estrogen and progestin hormones therapy (CHRT) are at greater risk of breast cancer. Yet, very few studies have focused on the impact of longer-term use of hormones therapy (HRT) (more than 15 years) after menopause and its effect on breast cancer risk. One study found that using hormones therapy for 5 years or more was linked to an increased risk, while another stated that only using hormones therapy for 10 years or longer increases breast cancer risk. The objective of this investigation is to analyze relationships between the duration of hormones therapy after menopause and risk of breast cancer.

Very little data is available on links between hormones therapy use post-menopause and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status. In this evaluation various factors were taken into consideration as potential contributors to breast cancer risk, including family history of breast cancer, type of menopause, and age at menopause. It was only adjustment for type of menopause that changed the risk estimates of the odds ratios (ORs), by more than 10%. Type of menopause was perhaps a confounder because estrogen hormones therapy (ERT) is associated with an increased risk of endometrial cancer but combined estrogen and progestin hormones therapy (CHRT) is not. Hence, estrogen hormones therapy is more likely to be a choice for females who have had a hysterectomy, and combined estrogen and progestin hormones therapy for women with an intact uterus.

Few investigations have examined the possible influence of hormones therapy use after menopause on rate of breast cancer by ER/PR status. One analysis reported that these associations were comparable regardless of ER/PR status, but another found that women using hormones therapy (HRT) after menopause were more likely to have hormone receptor-positive tumors. Yet, such studies did not distinguish between types of hormones therapy used after menopause.

Breast

 It was observed that use of estrogen hormones therapy after menopause was not related to risk of breast cancer of any ER/PR profile, but combined estrogen and progestin hormones therapy was associated with increases in risks of ER+/PR+ tumors, and that the scale of these risks increased the longer combined hormones therapy was used post- menopause. Even though such findings need to be confirmed, they indicate that the progestin component of combined estrogen and progestin hormones therapy is considerable in terms of altering the risk of breast cancer. Observations imply that combined hormones therapy after menopause may advance breast cancer by stimulating both ERs and PRs, and not through the ER alone, given that use of this combined hormones therapy was related to an increased risk of ER+/PR+ tumors, but not with a greater risk of ER+/PR- tumors.

Findings suggest that use of estrogen hormones therapy post-menopause does not increase the risk of breast cancer in women aged between 65 and 79 years, even among those using estrogen hormones therapy for 25 years or longer. A meta-analysis by the Collaborative Group on Hormonal Factors in Breast Cancer reported that current use of estrogen hormones therapy for 5 years or longer after menopause was linked to a 1.34-fold increased probability of breast cancer.

Data continues to be gathered about the adverse impact on breast cancer risk of adding progestin to hormones therapy (HRT). This adverse impact is evident within several years of starting hormones therapy after menopause. The data outlined above indicates that combined estrogen and progestin hormones therapy use after menopause is related to an increased risk of breast cancer, especially invasive lobular tumors.