Correction of climacteric disorders in patients with breast cancer: current methods and prospects
Treatment of menopausal syndrome in patients with breast cancer is aimed not only at maintaining the quality of life, but also at increasing life expectancy, including by reducing refusal rates of anti-recurrence therapy. The most effective treatment option is menopausal hormone therapy, which, with some exceptions, is contraindicated in patients with breast cancer. Phytoestrogens and serotonin-norepinephrine reuptake inhibitors are an alternative to relieve vasomotor symptoms. If non-hormonal treatment of genitourinary menopausal syndrome has no effect, estrogens should be considered for vaginal treatment. Promising treatment modalities include a tissue-selective estrogen complex, estetrol, ospemifene and vaginal dehydroepiandrosterone. Loss of bone mineral density and fractures in breast cancer patients has many causes. Effective treatments include bisphosphonates and denosumab.Smetnik A.A., Rodionov V.V., Kometova V.V.
Keywords
menopausal syndrome
breast cancer
genitourinary menopausal syndrome
vulvovaginal atrophy
osteoporosis
menopausal hormone therapy
phytoestrogens
antidepressants
References
- Fahlen M., Fornander T., Johansson H. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur. J. Cancer. 2013; 49(1): 52–9. https://dx.doi.org/10.1016/j.ejca.2012.07.003.
- Eden J. ENDOCRINE DILEMMA: Managing menopausal symptoms after breast cancer. Eur. J. Endocrinol. 2016; 174(3): R71–7. https://dx.doi.org/10.1530/EJE-15-0814.
- Wis´niewska I., Jochymek B., Lenart-Lipińska M., Chabowski M. The pharmacological and hormonal therapy of hot flushes in breast cancer survivors. Breast Cancer. 2016; 23(2): 178–82. https://dx.doi.org/10.1007/s12282-015-0655-2.
- Leon-Ferre R.A., Majithia N., Loprinzi C.L. Management of hot flashes in women with breast cancer receiving ovarian function suppression. Cancer Treat. Rev. 2017; 52: 82–90. https://dx.doi.org/10.1016/j.ctrv.2016.11.012.
- Vincent A.J. Management of menopause in women with breast cancer. Climacteric. 2015; 18(5): 690–701. https://dx.doi.org/10.3109/13697137.2014.996749.
- Hervik J.B., StubT. Adverse effects of non-hormonal pharmacological interventions in breast cancer survivors, suffering from hot flashes: A systematic review and meta-analysis. Breast Cancer Res. Treat. 2016; 160(2): 223–36. https://dx.doi.org/10.1007/s10549-016-4002-x.
- Fenlon D., Morgan A., Khambaita P., Mistry P., Dunn J., Ah-See M.L. et al. Management of hot flushes in UK breast cancer patients: clinician and patient perspectives. J. Psychosom. Obstet. Gynaecol. 2017; 38(4): 276–83. https://dx.doi.org/10.1080/0167482X.2017.1350163.
- Johns C., Seav S.M., Dominick S.A., Gorman J.R., Li H., Natarajan L. et al. Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions. Breast Cancer Res. Treat. 2016; 156(3): 415–26. https://dx.doi.org/10.1007/s10549-016-3765-4.
- Alipour S., Jafari-Adli S., Eskandari A. Benefits and harms of phytoestrogen consumption in breast cancer survivors. Asian Pac. J. Cancer Prev. 2015; 16(8): 3091–6. https://dx.doi.org/10.7314/apjcp.2015.16.8.3091.
- Einbond L.S., Wen-Cai Y., He K., Wu H.A., Cruz E., Roller M. et al. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. 2008; 15(6-7): 504–11. https://dx.doi.org/10.1016/j.phymed.2007.09.017.
- Fritz H., Seely D., McGowan J., Skidmore B., Fernandes R., Kennedy D.A. et al. Black cohosh and breast cancer: a systematic review. Integr. Cancer Ther. 2014; 13(1): 12–29. https://dx.doi.org/10.1177/1534735413477191.
- Leach M.J., Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst. Rev. 2012; (9): CD007244. https://dx.doi.org/10.1002/14651858.CD007244.pub2.
- Nikander E., Kilkkinen A., Metsä-Heikkilä M., Adlercreutz H., Pietinen P., Tiitinen A. et al. A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet. Gynecol. 2003; 101(6): 1213–20. https://dx.doi.org/10.1016/s0029-7844(03)00232-1.
- Сухих Г.Т., Сметник В.П., Юренева С.В., Ермакова Е.И., Чернуха Г.Е., Якушевская О.В. Клинические рекомендации «Менопауза и климактерическое состояние у женщины». М.; 2016. 45 с. [Sukhikh G.T., Smetnik V.P., Yureneva S.V., Ermakova E.I., Chernukha G.E., Yakushevskaya O.V. Klinicheskie rekomendatsii «Menopauza i klimaktericheskoe sostoyanie uzhenshchiny». Moscow; 2016. 45 p. (in Russian)].
- Dodin S., Blanchet C., Marc I., Ernst E., Wu T., Vaillancourt C. et al. Acupuncture for menopausal hot flushes. Cochrane Database Syst. Rev. 2013; (7): CD007410. https://dx.doi.org/10.1002/14651858.CD007410.pub2.
- Mann E., Smith M.J., Hellier J., Balabanovic J.A., Hamed H., Grunfeld E.A. et al. Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomized controlled trial. Lancet Oncol. 2012; 13(3): 309-18. https://dx.doi.org/10.1016/S1470-2045(11)70364-3.
- Ульрих Е.А., Урманчеева А.Ф. Онкологические аспекты заместительной менопаузальной гормональной терапии. Практическая онкология. 2009; 10(2): 76–83. [Ul’rikh E.A., Urmancheeva A.F. Onkologicheskie aspekty zamestitel’noi menopauzal’noi gormonal’noi terapii. Prakticheskaya onkologiya. 2009; 10(2): 76-83. (in Russian)].
- Harris B.S., Bishop K.C., Kuller J.A., Ford A.C., Muasher L.C., Cantrell S.E., Price T.M. Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy. Menopause. 2019; Oct. 31. https://dx.doi.org/10.1097/GME.0000000000001447.
- Cobleigh M.A., Berris R.F., Bush T., Davidson N.E., Robert N.J., Sparano J.A. et al. Estrogen replacement therapy in breast cancer survivors. A time for change. Breast Cancer Committees of the Eastern Cooperative Oncology Group. JAMA. 1994; 272(7): 540-5.
- DiSaia P.J., Grosen E.A., Kurosaki T., Gildea M., Cowan B., Anton-Culver H. Hormone replacement therapy in breast cancer survivors: a cohort study. Am. J. Obstet. Gynecol. 1996; 174(5): 1494–8.
- Vassilopoulou-Sellin R., Asmar L., Hortobagyi G.N., Klein M.J., McNeese M., Singletary S.E. et al. Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively. J. Clin. Oncol. 1999; 17(5): 1482–7. https://dx.doi.org/10.1200/JCO.1999.17.5.1482.
- O’Meara E.S., Rossing M.A., Daling J.R., Elmore J.G., Barlow W.E., Weiss N.S. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J. Natl. Cancer Inst. 2001; 93(10): 754-62. https://dx.doi.org/10.1093/jnci/93.10.754.
- Col N.F., Hirota L.K., Orr R.K., Erban J.K., Wong J.B., Lau J. Hormone replacement therapy after breast cancer: a systematic review and quantitative assessment of risk. J. Clin. Oncol. 2001; 19(8): 2357–63. https://dx.doi.org/10.1200/JCO.2001.19.8.2357.
- Holmberg L., Iversen O.E., Rudenstam C.M., Hammar M., Kumpulainen E., Jaskiewicz J. et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J. Natl. Cancer Inst. 2008; 100(7): 475–82. https://dx.doi.org/10.1093/jnci/djn058.
- Lupo M., Dains J.E., Madsen L.T. Hormone replacement therapy: an increased risk of recurrence and mortality for breast cancer patients? J. Adv. Pract. Oncol. 2015; 6(4): 322–30. https://dx.doi.org/10.6004/jadpro.2015.6.4.3.
- Kenemans P., Bundred N.J., Foidart J.M., Kubista E., von Schoultz B., Sismondi P. et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009; 10(2): 135–46. https://dx.doi.org/10.1016/S1470-2045(08)70341-3.
- The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017; 24(7): 728–53. https://dx.doi.org/10.1097/GME.0000000000000921.
- Kuhle C.L., Kapoor E., Sood R., Thielen J.M., Jatoi A., Faubion S.S. Menopausal hormone therapy in cancer survivors: A narrative review of the literature. Maturitas. 2016; 92: 86–96. https://dx.doi.org/10.1016/j.maturitas.2016.07.018.
- Gérard C., Mestdagt M., Tskitishvili E., Communal L., Gompel A., Silva E. et al. Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms. Oncotarget. 2015; 6(19): 17621–36. https://dx.doi.org/10.18632/oncotarget.4184.
- Pinkerton J.V., Conner E.A. Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators. Climacteric. 2019; 22(2): 140–7. https://dx.doi.org/10.1080/13697137.2019.1568403.
- Baumgart J., Nilsson K., Stavreus-Evers A., Kask K., Villman K., Lindman H. et al. Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer. Am. J. Obstet. Gynecol. 2011; 204(1): 26. e1–7. https://dx.doi.org/10.1016/j.ajog.2010.08.035.
- Gupta P., Sturdee D.W., Palin S.L., Majumder K., Fear R., Marshall T. et al. Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life. Climacteric. 2006; 9(1): 49–58. https://dx.doi.org/10.1080/13697130500487224.
- Fallowfield L.J., Kilburn L.S., Langridge C., Snowdon C.F., Bliss J.M., Coombes R.C. et al. Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation. Br. J. Cancer. 2012; 106(6): 1062–7. 10.1038/bjc.2012.43.
- Ganz P.A., Desmond K.A., Leedham B., Rowland J.H., Meyerowitz B.E., Belin T.R. et al. Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study. J. Natl. Cancer Inst. 2002; 94(1): 39–49. https://dx.doi.org/10.1093/jnci/94.1.39.
- Runowicz C.D., Leach C.R., Henry N.L., Henry K.S., Mackey H.T., Cowens-Alvarado R.L. et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. CA Cancer J. Clin. 2016; 66(1): 43–73. https://dx.doi.org/10.3322/caac.21319.
- Mazzarello S., Hutton B., Ibrahim M.F., Jacobs C., Shorr R., Smith S. et al. Management of urogenital atrophy in breast cancer patients: a systematic review of available evidence from randomized trials. Breast Cancer Res. Treat. 2015; 152(1): 1–8. https://dx.doi.org/10.1007/s10549-015-3434-z.
- Hickey M., Marino J.L., Braat S., Wong S. A randomized, double-blind, crossover trial comparing a silicone- versus water-based lubricant for sexual discomfort after breast cancer. Breast Cancer Res. Treat. 2016; 158(1): 79–90. https://dx.doi.org/10.1007/s10549-016-3865-1.
- Lee Y., Chung H., Kim J., Park N., Song Y., Kang S. Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial. Obstet. Gynecol. 2011; 117(4): 922–7. https://dx.doi.org/10.1097/AOG.0b013e3182118790.
- Goetsch M.F., Lim J.Y., Caughey A.B. A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial. J. Clin. Oncol. 2015; 33(30): 3394–400. https://dx.doi.org/10.1200/JCO.2014.60.7366.
- Salvatore S., Nappi R.E., Parma M., Chionna R., Lagona F., Zerbinati N. et al. Sexual function after fractional microablative CO₂ laser in women with vulvovaginal atrophy. Climacteric. 2015; 18(2): 219–25. https://dx.doi.org/10.3109/13697137.2014.899347.
- Donders G., Bellen G., Neven P., Grob P., Prasauskas V., Buchholz S. et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor ®) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res. Treat. 2014; 145(2): 371–9. https://dx.doi.org/10.1007/s10549-014-2930-x.
- Pfeiler G., Glatz C., Konigsberg R., Geisendorfer T., Fink-Retter A., Kubista E. et al. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric. 2011; 14(3): 339–44. https://dx.doi.org/10.3109/13697137.2010.529967.
- Ibe C., Simon J.A. Vulvovaginal atrophy: current and future therapies (CME). J. Sex. Med. 2010; 7(3): 1042–50. https://dx.doi.org/10.1111/j.1743-6109.2009.01692.x.
- Labrie F., Archer D.F., Koltun W., Vachon A., Young D., Frenette L. et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate-to-severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016; 23(3): 243–56. https://dx.doi.org/10.1097/GME.0000000000000571.
- Wurz G.T., Soe L.H., DeGregorio M.W. Ospemifene, vulvovaginal atrophy, and breast cancer. Maturitas. 2013; 74(3): 220–5. https://dx.doi.org/10.1016/j.maturitas.2012.12.002.
- Kagan R., Williams R., Pan K., Mirkin S., Pickar J. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate-to-severe vulvar/vaginal atrophy in postmenopausal women. Menopause. 2010; 17(2): 281–9. https://dx.doi.org/10.1097/GME.0b013e3181b7c65f.
- Sousa M.S., Peate M., Jarvis S., Hickey M., Friedlander M. A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy. Ther. Adv. Med. Oncol. 2017; 9(4): 269–85. https://dx.doi.org/10.1177/1758834016687260.
- Hadji P., Body J.J., Aapro M.S., Brufsky A., Coleman R.E., Guise T. et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann. Oncol. 2008; 19(8): 1407–16. https://dx.doi.org/10.1093/annonc/mdn164.
- Neuhouser M.L., Sorensen B., Hollis B.W., Ambs A., Ulrich C.M., McTiernan A. et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am. J. Clin. Nutr. 2008; 88(1): 133–9. https://dx.doi.org/10.1093/ajcn/88.1.133.
- Багрова С.Г., Копп М.В., Кутукова С.И., Манзюк Л.В., Семиглазова Т.Ю. Использование остеомодифицирующих агентов (ОМА) для профилактики и лечения патологии костной ткани при злокачественных новообразованиях. Злокачественные опухоли. Практические рекомендации RUSSCO. 2019; 9(3, Прил. 2): 576–84. [Bagrova S.G., Kopp M.V., Kutukova S.I., Manzyuk L.V., Semiglazova T.Yu. Ispol’zovanie osteomodifitsiruyushchikh agentov (OMA) dlya profilaktiki i lecheniya patologii kostnoi tkani pri zlokachestvennykh novoobrazovaniyakh. Zlokachestvennye opukholi. Prakticheskie rekomendatsii RUSSCO. 2019; 9(3, Suppl. 2): 576–84. (in Russian)]. https://dx.doi.org/10.18027 / 2224-5057-2019-9-3s2-576-584.
Received 27.12.2019
Accepted 30.12.2019
About the Authors
Antonina A. Smetnik, PhD, Senior Researcher, Department of Gynecological Endocrinology, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.. Tel.: +74955314444, ext. 1543. E-mail: a_smetnik@oparina4.ru117997, Russia, Moscow, Ac. Oparina str. 4
Valeriy V. Rodionov, MD, Head of the Department of Breast Pathology, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
Tel.: +79265626590. E-mail: V_Rodionov@oparina4.ru
117997, Russia, Moscow, Ac. Oparina str. 4.
Vlada V. Kometova, MD, Senior Researcher of Department of Pathological Anatomy, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +79265626590. E-mail: v_kometova@oparina4.ru
117997, Russia, Moscow, Ac. Oparina str. 4.
For citation: Smetnik A.A., Rodionov V.V., Kometova V.V. Correction of climacteric disorders in patients with breast cancer: current methods and prospects.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 1(Suppl): 26-33. (in Russian)
https://dx.doi.org/10.18565/aig.2020.1suppl.26-33