Can Some Cancer Patients Take Hormone Replacement Therapy?

When someone receives the diagnosis of cancer, life changes forever. Just one minute before, that individual and her family led normal lives. Never more. They suddenly are flooded with questions. “What does this mean? What can be done? Do I need a second opinion? Do I need surgery, chemotherapy, radiation therapy, and/or immunotherapy? Am I going to die? And again, what did you just say?”

Our fear of cancer drives much of our preventive health care. Mammograms, Pap smears, annual examinations, colonoscopies, all are targeted at ruling out cancer. As affirmation of these efforts, however, the National Cancer Institute reports that the number of people living after a cancer diagnosis was almost 14.5 million in 2014 and is expected to rise to almost 19 million by 2024. How we follow these people and improve their quality of life is a work in progress.

For many women, the aftermath of several treatments for cancer involves the loss of reproductive capabilities and cessation of hormone production. Because of radiation, chemotherapy, and/or surgery to remove the uterus and ovaries, many women find themselves thrust into menopause. With the loss of ovarian estradiol, these women are likely to experience menopausal symptoms including hot flashes, mood swings, sleep disorders, bone loss, and vaginal atrophy. For some, the symptoms may be so acute as to lead them to consider whether the benefits of hormone replacement therapy (HRT) are more desirable than the possibility that hormone supplementation may enhance the risks of cancer recurrence or the occurrence of a new cancer.

Absent cancer, those same women at some stage of their lives may benefit from hormone replacement therapy. A common response from many care providers is, “No hormones for you, because of your cancer.” That common response is not exactly true as newer research demonstrates. Nonetheless, accepting conclusions of most cancer studies must be tempered by whether the hormones used were estrogen replacement therapy (ERT) only (women with hysterectomy) or estrogen plus progesterone (HRT), as well as differences in age of study participants, type and degree of cancer stage, length of observation, confounding health issues, and changing treatments over time. Still, a trend seems to be developing that underscores possible differences in a variety of cancers for women who receive estrogen alone versus those who are given estrogen and progesterone.

Breast cancer is the most common cancer in women of all races. In the 1940s and 1950s, women with advanced or metastatic breast cancer were treated with high-dose estrogen (diethylstilbestrol-DES) with one-third of women responding favorably. Many years later, while women from the Women’s Health Initiative (WHI) given HRT with Premarin® and medroxyprogesterone (PremPro®) showed a small increase in breast cancer over non-treated women, those with a hysterectomy receiving estrogen replacement therapy (ERT) only (Premarin®) showed a reduced incidence of breast cancer. Young women who carry BRCA mutations who elect to remove their fallopian tubes and ovaries prophylactically after childbearing and who choose to take ERT have not been found to have an increased risk in breast cancer in small studies.

Lung cancer is the second most frequent cancer among white and black women and third among Hispanic women. In a meta-analysis of 14 cohort studies, no increased risk was found for developing lung cancer if HRT (not defined) was used. When a prospective cohort of 36,588 women with lung cancer was studied, the combination of estrogen plus progesterone (HRT) increased the risk of incident lung cancer, but estrogen alone (ERT) produced no such association.

Colorectal cancer is the second most common cancer among Hispanic women and third among white and black women. From a cohort of 7,701 women who were initially free of cancer but were placed on estrogen only replacement therapy, ERT was associated with a reduced cancer risk when compared with non-users.

Endometrial cancer is the most treatable of women’s cancers. Standard treatment consists of removal of the uterus and ovaries, along with a sampling of lymph nodes. In one study of 1,236 endometrial cancer survivors, of which 618 were placed on ERT versus those on placebo after surgery and followed for 35.7 months, the recurrence rate was very low, 3.1% in the placebo group and 0.6% in the ERT group.

Ovarian cancer recurrence risk with ERT was examined in the Adjuvant Hormone Therapy trial initiated in 1990. One hundred and fifty women were studied, with 75 using ERT and 75 as non-users. Estrogen replacement therapy users exhibited fewer recurrences, longer disease-free intervals, and improved survival.

Cervical cancer recurrences and HRT was studied in 120 survivors after surgery and/or radiotherapy for stage 1 and 2 cancers. No significant increase in recurrences or survival was observed for HRT users (N=80) compared with non–users (N=40).

The safety of HRT versus ERT to treat menopausal symptoms in cancer survivors will never be absolute until our understanding of what causes cancer is complete. Why ERT only, as opposed to HRT, would seem to offer some protection against cancer of most types remains an enigma. One could postulate that the anti-inflammatory properties of estrogen reduce the incidence of mutation-derived cell change. Despite lacking a clear explanation, the emotional trauma of learning one has cancer should not, de facto, prevent a discussion of available studies of hormone therapy for menopausal symptoms. All a cancer survivor wants is to live a life of quality. Care providers should use that as a guide.

By James Woods, M.D., and Elizabeth Warner, M.D.

James Woods | 4/7/2017

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