Seminars in Oncology
Volume 33, Issue 6 , Pages 696-707 , December 2006

Management of Postmenopausal Symptoms in Breast Cancer Survivors

  • Debora Bruno

      Affiliations

    • Current address for D.B.: Nebraska Cancer Care, 815 N Kansas Ave, Suite 100, Hastings, NE 68901.
  • ,
  • Kendra J. Feeney

      Affiliations

    • Corresponding Author InformationAddress correspondence to Kendra Feeney, MD, Division of Medical Oncology, Thomas Jefferson University Hospital, 125 S 9th St, Sheridan Building, Suite 801, Philadelphia, PA, 19107.

References 

  1. In:  Ries LAG,  Eisner MP,  Kosary CL, et al. editor. SEER Cancer Statistics Review, 1975-2002. Bethesda, MD: National Cancer Institute; 2005;
  2. Ganz PA, Greendale GA, Petersen L, et al. Breast cancer in young women: Reproductive and late health effects of treatment. J Clin Oncol. 2003;21:4184–4193
  3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333
  4. Holmberg L, Anderson H, Steering H. HABITS (hormonal replacement therapy after breast cancer: is it safe?), a randomized comparison: Trial stopped. Lancet. 2004;363:453–455
  5. Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of WHO: Technical report Series 670: Research on the Menopause. Geneva, Switzerland: WHO; 1991;
  6. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996;14:1718–1729
  7. Molina JR, Barton DL, Loprinzi CL. Chemotherapy-induced ovarian failure: Manifestations and management. Drug Safety. 2005;28:401–416
  8. Warne GL, Fairley KF, Hobbs JB, et al. Cyclophosphamide-induced ovarian failure. N Engl J Med. 1973;289:1159–1162
  9. Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol. 1997;17:2365–2370
  10. Fornier MN, Modi S, Hudis CA, et al. MHSHC: Incidence of amenorrhea (A) in breast cancer patients (pts) < 40 years of age after paclitaxel (T)-based adjuvant chemotherapy (CT). Breast Cancer Res Treat. 2002;76:A645;(suppl 1, abstr)
  11. Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: A hypothesis of flush mechanism. Clin Endocrinol. 1985;22:293–312
  12. Keenan NL, Mark S, Fugh-Berman , et al. Severity of menopausal symptoms and use of both conventional and complementary alternatives. Menopause. 2003;10:507–515
  13. Li C, Samsioe G, Borgfeldt C, et al. Menopause-related symptoms; what are the background factors? (A prospective population-based cohort study of Swedish women (The Women’s Health in Lund Area Study)). Am J Obstet Gynecol. 2003;189:1646–1653
  14. Haimov-Kochman R, Hochner-Celnikier D. Hot flashes revisited: Pharmacological and herbal options for hot flashes management (What does the evidence tell us?). Acta Obstet Gynecol Scan. 2005;84:972–979
  15. MacLennan AH, Broadbent JL, Lester S, et al. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flashes. Cochrane Database Syst Rev. 2005;(Issue 4):CD 002978
  16. Tham DM, Gardner CD, Haskell W. Potential health benefits of dietary phytoestrogens: A review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223–2235
  17. Quella SK, Loprinzi CL, Barton D, et al. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol. 2000;18:1068–1074
  18. Tice JA, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: The Isoflavone Clover Extract (ICE) study—A randomized controlled trial. JAMA. 2003;290:207–214
  19. Krebs E, Ensrud K, Macdonald R, et al. Phytoestrogens for treatment of menopausal symptoms; a systematic review. Obstet Gynecol. 2004;104:824–836
  20. Barton DL, Loprinzi CL, Quella SK, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer patients. J Clin Oncol. 1998;16:495–500
  21. Miller ER, Pasrot-Barriuso R, Dalal D, et al. Meta-analysis: High-dose vitamin E supplementation may increase all cause mortality. Ann Intern Med. 2005;142:37–46
  22. Viereck V, Emons G, Wuttke W. Black cohosh: Just another phytoestrogen?. Trends Endocr Metabol. 2005;16:214–221
  23. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol. 2001;19:2739–2745
  24. Osmers R, Friede M, Liske E, et al. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol. 2005;105:1074–1083
  25. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust. 2002;177:440–443
  26. Lontos S, Jones RM, Angus PW, et al. Acute liver failure associated with the use of herbal preparations containing black cohosh. MJA. 2003;179:390–391
  27. Levitsky J, Alli TA, Wisecarver J, et al. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci. 2005;50:538–539
  28. Rockwell S, Yanfeng L, Higgins S. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat. 2005;90:233–239
  29. Mahady GB. Black cohosh (Actaea/Cimicifuga racemosa): Review of the clinical data for safety and efficacy in menopausal symptoms. Treat Endocrinol. 2005;4:177–184
  30. Pandya KJ, Raubertas RF, Flynn PJ, et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: A University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med. 2000;132:788–793
  31. Goldberg RM, Loprinzi CL, O’Fallon JR. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol. 1994;12:155–158
  32. Klaiber EL, Kobayashi Y, Broverman DM. Plasma monoamine oxidase activity in regularly menstruating women and in amenorheic women receiving cyclic treatment with estrogens and progestins. J Clin Endocrinol Metab. 1971;33:603–638
  33. Gonzalez GF, Carrillo C. Blood serotonin levels in postmenopausal women: Effects of age and serum oestradiol levels. Maturitas. 1993;17:23–29
  34. Sherwin BB. Hormones, mood, and cognitive functioning in menopausal women. Obstet Gynecol. 1996;87:20S–26S
  35. Loprinzi CL, Pisansky TM, Fonseca R, et al. Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. J Clin Oncol. 1998;16:2377–2381
  36. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: A randomized controlled trial. Lancet. 2000;356:2059–2063
  37. Stearns V, Isaacs C, Rowland J, et al. A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer patients. Ann Oncol. 2000;11:17–22
  38. Weitzner MA, Moncello J, Jacobsen PB, et al. A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. J Pain Symptom Manage. 2002;23:337–345
  39. Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002;20:1578–1583
  40. Furr BJ, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacol Ther. 1984;25:127–205
  41. Stearns V, Johnson MD, Rae JM, et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003;95:1758–1764
  42. Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: A randomized double-blind placebo-controlled trial. Lancet. 2005;366:818–824
  43. Guttuso TJ, Kurlan R, McDermott MP, et al. Gabapentin’s effects on hot flashes in post-menopausal women: A randomized controlled trial. Obstet Gynecol. 2003;101:337–345
  44. Struble EJ, Dice Y, Ornstein DL, et al. Gabapentin versus venlafexine for the treatment of menopausal symptoms: A preliminary report. Breast Cancer Res Treat. 2004;88(suppl 1):240–241
  45. Loprinzi CL, Michalak JC, Quella SK, et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med. 1994;331:347–352
  46. Quella SK, Loprinzi CL, Sloan JA, et al. Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes. Cancer. 1998;82:1784–1788
  47. Bertelli G, Venturini M, del Mastro L, et al. Intramuscular depot of medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: A randomized study. Ann Oncol. 2002;13:883–888
  48. Barton D, Loprinzi CL, Sloan JA, et al. Depomedroxyprogesterone acetate for hot flashes. J Pain Symptom Manage. 2002;24:603–607
  49. Wingo PA, Tong T, Bolden S. Cancer statistics. CA Cancer J Clin. 1995;45:8–30
  50. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–1767
  51. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy. Osteoporosis prevention, diagnosis and therapy. JAMA. 2001;285:785–795
  52. Raisz LG, Kream BE, Lorenzo JA. Metabolic bone disease. In:  Larsen PR editors. Williams Textbook of Endocrinology. (ed 10).. Philadelphia, PA: Saunders; 2003;p. 1373–1402
  53. Kanis JA WHO Study Group. Assessment of fracture risk and its application to screening for post-menopausal osteoporosis: Synopsis of a WHO report. Osteoporos Int. 1994;4:368–381
  54. In:  Favus MJ editors. Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism. (ed 4).. Philadelphia, PA: Lippincott; 1999;
  55. Ramaswamy B, Shapiro CL. Osteopenia and osteoporosis in women with breast cancer. Semin Oncol. 2003;30:763–775
  56. Bord S, Ireland DC, Beavan SR, et al. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone. 2003;32:136–141
  57. Prince RL. Counterpoint: estrogen effects on calcitotropic hormones and calcium homeostasis. Endocrine Rev. 1994;15:301–309
  58. Cummings SR, Browner WS, Bauer D, et al. Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med. 1998;339:733–738
  59. Van Poznak C, Sauter NP. Clinical management of osteoporosis in women with a history of breast carcinoma. Cancer. 2005;104:443–456
  60. Shapiro CL, Manola J, Leboth M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol. 2001;19:3306–3311
  61. Turner RT, Wakley GK, Hannon KS, et al. Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats. Endocrinology. 1998;122:1146–1150
  62. Love RR, Mazess BB, Bauden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992;326:852–856
  63. Kristensen B, Ejlertsen B, Mouridsen HT, et al. Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: A randomized study. J Clin Oncol. 1994;12:992–997
  64. Powles TJ, Hickish T, Kanis JA, et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996;14:78–84
  65. Fisher B, Constantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. JNCI Cancer Spectrum. 1998;90:1371–1388
  66. Clement D, Spencer CM. Raloxifene: A review of its use in postmenopausal osteoporosis. Drugs. 2000;60:379–411
  67. Delmas PD, Ensrud KE, Adachi JD, et al. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: Four-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2002;87:3609–3617
  68. O’Regan RM, Jordan VC. Tamoxifen to raloxifene and beyond. Semin Oncol. 2001;28:260–273
  69. Baum M, Budzar AV, Cuzick L, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomized trial. Lancet. 2002;359:2131–2139
  70. ATAC Trialists’ Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of post-menopausal women with early-stage breast cancer: Results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analysis. Cancer. 2003;98:1802–1810
  71. Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med. 2003;348:2431–2442
  72. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327:1637–1642
  73. Reid IR, Ames RW, Evans MC, et al. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: A randomized controlled trial. Am J Med. 1995;98:331–335
  74. Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670–676
  75. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669–683
  76. Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003;21:4042–4047
  77. Delmas PD, Balena R, Confravreux E, et al. Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: A double-blind, placebo-controlled study. J Clin Oncol. 1997;15:955–962
  78. Gnant M, Hausmaninger H, Samonigg H, et al. Changes in bone mineral density caused by anastrozole or tamoxifen in combination with goserelin (+/− zoledronate) as adjuvant treatment for hormone receptor-positive breast cancer: Results of a randomized multicenter trial. Breast Cancer Res Treat. 2002;76:531;(suppl 1, abstr)
  79. Brufsky A, Harker G, Beck T, et al: Zoledronic acid for prevention of cancer treatment-induced bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Preliminary reports of the Z-FAST trial. Presented at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, CA, December 8-11, 2004
  80. Iosif CS, Batra S, Ek A, et al. Estrogen receptors in the female urinary tract. Am J Obstet Gynecol. 1981;141:817–820
  81. Smith P, Heimer GM, Norgren A, et al. Steroid hormone receptors in pelvic muscles and ligaments in women. Gynecol Obstet Invest. 1990;30:27–30
  82. Bachman GA. Diagnosis and treatment of atrophic vaginits. Am Fam Phys. 2003;61:3090–3096
  83. SOGC Clinical Practice Guidelines. The detection and management of vaginal atrophy. Int J Gynecol Obstet. 2005;88:222–228
  84. Cardozo L, Bachmann G, McClish D, et al. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: Second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998;92:722–727
  85. Ganz PA, Desmond KA, Belin TR, et al. Predictors of sexual health in women after a breast cancer diagnosis. J Clin Oncol. 1999;17:2371–2380
  86. Loprinzi CL, Abu-Ghazaleh S, Sloan JA, et al. Phase III randomized double-blind study to evaluate the efficacy of a polucarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol. 1997;15:969–973
  87. Mandel FP, Geola FL, Meldrum DR, et al. Biological effects of various doses of vaginally administered conjugated equine estrogens in postmenopausal women. J Clin Endocrinol Metab. 1983;57:133–139
  88. Handa VL, Bachus KE, Johnston WW, et al. Vaginal administration of low-dose conjugated estrogens: Systemic absorption and effects on endometrium. Obstet Gynecol. 1994;84:215–218
  89. Notelovitz M, Funk S, Nanavati N, et al. Estradiol absorption from vaginal tablets in postmenopausal women. Obstet Gynecol. 2002;99:556–562
  90. Rioux JE, Devlin C, Gelfand MM, et al. 17-Beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7:156–161
  91. Simunic V, Banovic I, Ciglar S, et al. Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet. 2003;82:187–197
  92. Dew JE, Wren BG, Eden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric. 2003;6:45–52
  93. Kendall A, Dowsett M, Folkerd E, et al. Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol. 2006;17:584–587
  94. Casper F, Petri E Vaginal Ring Study Group. Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10:171–176
  95. Speroff L. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol. 2003;102:823–834
  96. Phillips NA. Female sexual dysfunction: evaluation and treatment. Am Fam Physician. 2000;62:127–136
  97. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: Prevalence and predictors. JAMA. 1999;281:537–544
  98. Barni S, Mondin R. Sexual dysfunction in treated breast cancer patients. Ann Oncol. 1997;8:149–153
  99. Mortiner JE, Boucher L, Baty J, et al. Effect of tamoxifen on sexual functioning in patients with breast cancer. J Clin Oncol. 1999;17:1488–1492
  100. Shifren JL. The role of androgens in female sexual dysfunction. Mayo Clin Proc. 2004;79(suppl):S19–S24
  101. Lang WR. Vaginal acidity and pH: A review. Obstet Gynecol Surv. 1955;10:546–560
  102. Molander U, Milsom I, Ekelund P, et al. Effect of oral oestriol on vaginal flora and cytology and urogenital symptoms in the post-menopause. Maturitas. 1990;12:113–120
  103. Klebanoff SJ, Hillier SL, Eschenbach DA, et al. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis. 1991;164:94–100
  104. Stamey TA, Sexton CC. The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol. 1975;113:214–217
  105. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993;329:753–756
  106. Eriksen BC. A randomized, open, parallel-group study on the preventive effect of estradiol-releasing vaginal ring on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999;180:1072–1079
  107. Dessole L, Rubattu G, Ambrosini G. Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. Menopause. 2004;11:49–56
  108. Raz R. Hormone replacement therapy or prophylaxis in postmenopausal women with recurrent urinary tract infection. J Infect Dis. 2001;183:S74–S76
  109. Levi F, Randimbison L, Te VC, et al. Long-term mortality of women with a diagnosis of breast cancer. Oncology. 2002;63:266–269
  110. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: A quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63
  111. Gabriel-Sanchez R, Carmona L, Roque M, et al. Hormone replacement therapy for preventing cardiovascular disease in postmenopausal women. Cochrane Database Syst Rev. 2005;Vol 4:
  112. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998;280:605–613
  113. Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation. 2004;109:672–693
  114. Wood AJJ. Selective estrogen-receptor modulators—Mechanism of action and application in clinical practice. N Engl J Med. 2003;348:618–629
  115. Bundred NJ. The effects of aromatase inhibitors on lipids and thrombosis. Br J Cancer. 2005;93(suppl 1):S23–S27
  116. Dewar J, Nabholtz J-MA, Bonneterre J, et al. The effect of anastrozole (Arimidex) on serum lipids—Data from a randomized comparison of anastrozole (AN) versus tamoxifen (TAM) in postmenopausal women (PM) with advanced breast cancer (ABC). Breast Cancer Res Treat. 2000;64:51;(abstr)
  117. Banerjee S, Smith IE, Folkerd L, et al. Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone derived resorption during neoadjuvant therapy in the IMPACT trial. Ann Oncol. 2005;16:1632–1638
  118. Walsan KM, Goss PE, Pritchard PH. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCI CTG MA.17L). Ann Oncol. 2005;16:707–715
  119. Atalay G, Dirix L, Biganzoli L, et al. The effect of exemestane on serum lipid profile on postmenopausal women with metastatic breast cancer: A companion study to EORTC trial 10951, ‘Randomized phase II study in first line hormonal therapy for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients’. Ann Oncol. 2004;12:211–217
  120. Subar M, Goss PE, Thomsen T, et al. Effects of steroidal and non-steroidal aromatase inhibitors (AIs) on markers of bone turnover and lipid metabolism in healthy volunteers. J Clin Oncol. 2004;22:14S;(abstr)

PII: S0093-7754(06)00321-6

doi: 10.1053/j.seminoncol.2006.08.010

Seminars in Oncology
Volume 33, Issue 6 , Pages 696-707 , December 2006