Managing Menopausal Symptoms in Breast Cancer Survivors

With an estimated 5-year survival rate of 90%, most breast cancer cases have a very favorable prognosis.¹ In developed countries, the 5-year survival rate for patients with localized disease is approximately 99%.² It is not surprising then that approximately 6 million women worldwide live with a past breast cancer diagnosis and are focused on managing the long-term consequences of their treatment.³

Additionally, many women face menopausal symptoms or symptoms associated with estrogen deficiency during or on completion of breast cancer treatment.⁴ These include sleep disturbances, hot flashes, vulvovaginal atrophy, depressive symptoms, mood swings, bone loss, and cardiovascular disease. In certain women, menopausal symptoms after treatment are more severe than the symptoms of natural menopause in women who never had breast cancer.^3,5 

Complicating things further, many clinicians advise the discontinuation of hormone treatment in breast cancer survivors for fear of its mitogenic effects and the risk for triggering recurrent disease,^4,6 which one trial estimated to be threefold in women receiving hormone replacement therapy.⁷

In an interview with Endocrinology Advisor, Susan R. Davis, MBBS, PhD, FRACP, chair of Women’s Health Program at the School of Public Health and Preventive Medicine, Monash University, in Melbourne, Australia, and Richard J. Santen, MD, professor of medicine at the University of Virginia in Charlottesville, discussed the effects of breast cancer treatment on menopausal symptoms in women and available treatment options for their management.

Endocrinology Advisor: What is the incidence of breast cancer in menopause-age women vs premenopausal and postmenopausal women?

Susan Davis, MBBS, PhD, FRACP: Breast cancer incidence increases with age, and the statistics for Australia are available online. Natural menopause occurs anywhere between age 40 and 58 years and breast cancer incidence increases during these years associated with age, not menopause.

Endocrinology Advisor: How does chemotherapy for breast cancer affect the onset and severity of menopausal symptoms in these 3 age groups?

Dr Davis: The effects of chemotherapy on ovarian function vary with the type of treatment used and a woman’s age. A woman in her 30s may experience loss of ovarian function but may recover ovarian function after the treatment is over. However, in such a young person, it is often recommended that treatment be used to switch off ovarian function to improve the prognosis. Chemotherapy for breast cancer is likely to cause acute ovarian failure in a woman who is approaching menopause, and this is commonly associated with acute and severe menopausal symptoms. In women who are perimenopausal or postmenopausal, chemotherapy may exacerbate menopausal symptoms. Postmenopausal women who are taking hormone therapy for menopausal symptoms are advised to stop when breast cancer is diagnosed and this in itself often results in recurrent symptoms that were the reason for hormone therapy in the first place.

Endocrinology Advisor: Are menopausal symptoms more prevalent and/or severe in women with a past diagnosis of breast cancer who are not taking adjuvant endocrine therapy? In your study of menopausal symptoms in breast cancer survivors published in Menopause,⁸ which symptoms were the most pronounced in this population of women?

Dr Davis: We have found menopausal symptoms to be highly prevalent in breast cancer survivors and cannot be predicted by whether or not a woman has had chemotherapy or been treated with endocrine therapy. Seventy-two percent of women age 50 to 59 years not on endocrine therapy had hot flashes and night sweats. Compared with age-matched community controls, women who had been treated for breast cancer previously had more severe hot flashes and night sweats and more severe sexual symptoms, mostly as a result of vaginal dryness.

Endocrinology Advisor: What are some considerations that need to be taken into account when selecting the optimal management approach for menopausal symptoms in women with a past breast cancer diagnosis?

Richard J. Santen, MD: The first consideration is that menopausal hormone therapy is considered to be relatively contraindicated in women with a past breast cancer diagnosis. The next is to determine whether the symptoms are mild and not very bothersome; or moderate or severe and bothersome. Lifestyle modifications are suggested if symptoms are mild, and if severe, the precise symptoms are identified and specific treatment suggested. In each woman, the treatment is tailored to her own specific needs.

Endocrinology Advisor: What are some of the non-hormone treatment modalities available for treatment of menopausal symptoms, such as the commonly experienced hot flashes, in breast cancer survivors?

Dr Santen: In women with mild symptoms of hot flashes, avoidance of hot rooms, dressing in layers to allow removal of a sweater during hot flashes, for example, carrying a portable fan, and avoiding stress and spicy foods are suggested. If the symptoms are moderate or severe, it is determined whether the hot flashes are primarily at night and cause frequent awakening. If so, gabapentin is a very useful agent. If the hot flashes occur primarily during the daytime, drugs such as brisdelle or Effexor^® are useful. For vulvovaginal atrophy, chronic use of a vaginal moisturizer such as Replens™ and acute use of a vaginal lubricant just prior to intimacy are suggested. In women with a very low risk for breast cancer recurrence, ultra-low dose vaginal estrogen can be used after consultation with the patient’s oncologist.

Endocrinology Advisor: Can you identify any promising new therapies suitable for management of menopausal symptoms in this population?

Dr Santen: One of the drugs used for vulvovaginal atrophy, ospemiphene, is useful and is an approved drug for women without breast cancer. When studies show the safety of this agent in women with breast cancer, we expect it to also become a treatment option for this population. It is very exciting that drugs are being developed that act at the specific site of the brain which initiates hot flashes — the hypothalamus. The temperature-regulating system is controlled there by KNDy neurons. Two agents, Fezolinetant (ESN 363) and MLE 4901, appear to be very effective in clinical trials for blocking hot flashes without major side effects and will be considered a breakthrough for treating hot flashes if approved by the FDA. Descriptions of these agents can be found in abstracts of ENDO 2016 – The Endocrine Society 98th Annual Meeting and Expo. 

References

1. American Cancer Society. Cancer Treatment & Survivorship Facts and Figures: 2014-2015. Atlanta, Georgia: American Cancer Society; 2014.
2. American Cancer Society. Cancer Facts & Figures 2017. Atlanta, Georgia: American Cancer Society; 2017.
3. Cohen PA, Brennan A, Marino JL, Saunders CM, Hickey M. Managing menopausal symptoms after breast cancer – a multidisciplinary approach [published online April 22, 2017]. Maturitas. doi:10.1016/j.maturitas.2017.04.013
4. Santen RJ, Stuenkel CA, Davis SR, et al. Managing menopausal symptoms and associated clinical issues in breast cancer survivors [published online August 2, 2017]. J Clin Endocrinol Metab. doi:10.1210/jc.2017-01138
5. Mortimer J, Behrendt CE. Severe menopausal symptoms are widespread among survivors of breast cancer treatment regardless of time since diagnosis. J Palliat Med. 2013;16:1130-1134.
6. Oyarzún MFG, Castelo-Branco C. Use of hormone therapy for menopausal symptoms and quality of life in breast cancer survivors. Safe and ethical? Gynecol Endocrinol. 2017;33:10-15.
7. Holmberg L, Iversen O-E, Rudenstam CM, et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J. Natl Cancer Inst. 2008;100:475-482.
8. Davis SR, Panjari M, Robinson PJ, Fradkin P, Bell RJ. Menopausal symptoms in breast cancer survivors nearly 6 years after diagnosis. Menopause. 2014;21:1075-1081.