Supportive Care in Cancer

, Volume 21, Issue 5, pp 1461–1474 | Cite as

Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations

  • Sylvain L’Espérance
  • Suzanne FrenetteEmail author
  • Anne Dionne
  • Jean-Yves Dionne
  • Comité de l’évolution des pratiques en oncologie (CEPO)
Review Article



Breast cancer patients frequently report hot flashes. Given that conventional hormone replacement therapy is generally contraindicated for them, other therapeutic modalities must be considered. The purpose of this review was to develop evidence-based recommendations on non-hormonal pharmacological interventions, including natural health products, for managing hot flashes in women undergoing treatment for breast cancer or with a history of breast cancer.


A review of the scientific literature published between January 2000 and December 2011 was performed. A total of 26 randomized trials were identified.


Studies showed that serotonin–norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, antihypertensives and anticonvulsants significantly reduced the frequency and severity of hot flashes in breast cancer patients.


Considering the evidence available to date, the CEPO recommends the following: (1) for breast cancer patients being treated with tamoxifen: (a) the use of venlafaxine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) the use of paroxetine and fluoxetine be avoided, given that they may reduce the efficacy of tamoxifen; (2) for breast cancer patients not being treated with tamoxifen: (a) the use of venlafaxine, paroxetine, citalopram, clonidine, gabapentin and pregabalin be considered effective in treating hot flashes and (b) fluoxetine not be used to treat hot flashes, given that there is insufficient evidence for its therapeutic efficacy and (3) for breast cancer survivors, sertraline, phytoestrogens, black cohosh and St. John’s wort not be used to treat hot flashes.


Hot flashes Breast cancer Antidepressants Antihypertensives Anticonvulsants Natural health products 



The CEPO is a group of oncology specialists that reports to the Direction québécoise de cancérologie du ministère de la Santé et des Services sociaux du Québec. La Direction québécoise de cancérologie provided funding for the work reported in this article, which is an adaptation of CEPO’s original clinical practice guideline published in June 2012, available in French at The CEPO would like to thank Jamil Asselah MD, Montreal General Hospital (MUHC); Amélie Chartier B.Pharm./M.Sc./BCOP, Montreal General Hospital (MUHC); Renée Simon MD, Hôpital Charles LeMoyne; Dominique Synnott MD, Hôpital du Sacré-Cœur de Montréal and Lucie Vaillancourt MD, Hôpital du St-Sacrement (CHU de Québec) for their contribution as external reviewers for the original clinical practice guideline.


The authors have no financial conflicts of interest to declare.


  1. 1.
    Comité Directeur de la Société Canadienne du Cancer. Statistiques Canadiennes sur le Cancer 2012. Société Canadienne du Cancer, TorontoGoogle Scholar
  2. 2.
    Boekhout AH, Beijnen JH, Schellens JH (2006) Symptoms and treatment in cancer therapy-induced early menopause. Oncologist 11(6):641–654. doi: 10.1634/theoncologist.11-6-641 PubMedCrossRefGoogle Scholar
  3. 3.
    Debourdeau P, Bachelot T, Zammit C, Aletti M, Gallineau C, Gligorov J (2004) Treatment of hot flashes in women with a previous diagnosis of breast cancer. Bull Cancer 91(4):339–349PubMedGoogle Scholar
  4. 4.
    Dalal S, Zhukovsky DS (2006) Pathophysiology and management of hot flashes. J Support Oncol 4(7):315–320, 325PubMedGoogle Scholar
  5. 5.
    Carpenter JS (2001) The hot flash related daily interference scale: a tool for assessing the impact of hot flashes on quality of life following breast cancer. J Pain Symptom Manag 22(6):979–989CrossRefGoogle Scholar
  6. 6.
    Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E (1996) A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 24(3):161–175PubMedCrossRefGoogle Scholar
  7. 7.
    Thirlaway K, Fallowfield L, Cuzick J (1996) The sexual activity questionnaire: a measure of women’s sexual functioning. Qual Life Res 5(1):81–90PubMedCrossRefGoogle Scholar
  8. 8.
    Wiklund I, Holst J, Karlberg J, Mattsson LA, Samsioe G, Sandin K, Uvebrant M, von Schoultz B (1992) A new methodological approach to the evaluation of quality of life in postmenopausal women. Maturitas 14(3):211–224PubMedCrossRefGoogle Scholar
  9. 9.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333PubMedCrossRefGoogle Scholar
  10. 10.
    Beral V (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362(9382):419–427PubMedCrossRefGoogle Scholar
  11. 11.
    Col NF, Hirota LK, Orr RK, Erban JK, Wong JB, Lau J (2001) Hormone replacement therapy after breast cancer: a systematic review and quantitative assessment of risk. J Clin Oncol 19(8):2357–2363PubMedGoogle Scholar
  12. 12.
    von Schoultz E, Rutqvist LE (2005) Menopausal hormone therapy after breast cancer: the Stockholm randomized trial. J Natl Cancer Inst 97(7):533–535. doi: 10.1093/jnci/dji071 CrossRefGoogle Scholar
  13. 13.
    Holmberg L, Anderson H (2004) HABITS (hormonal replacement therapy after breast cancer—is it safe?), a randomised comparison: trial stopped. Lancet 363(9407):453–455. doi: 10.1016/S0140-6736(04)15493-7 PubMedCrossRefGoogle Scholar
  14. 14.
    Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, Jassem J, Dobaczewska D, Fjosne HE, Peralta O, Arriagada R, Holmqvist M, Maenpaa J (2008) Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst 100(7):475–482. doi: 10.1093/jnci/djn058 PubMedCrossRefGoogle Scholar
  15. 15.
    Carpenter JS, Storniolo AM, Johns S, Monahan PO, Azzouz F, Elam JL, Johnson CS, Shelton RC (2007) Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist 12(1):124–135. doi: 10.1634/theoncologist.12-1-124 PubMedCrossRefGoogle Scholar
  16. 16.
    Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ (2000) Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 356(9247):2059–2063. doi: 10.1016/S0140-6736(00)03403-6 PubMedCrossRefGoogle Scholar
  17. 17.
    Boekhout AH, Vincent AD, Dalesio OB, van den Bosch J, Foekema-Tons JH, Adriaansz S, Sprangers S, Nuijen B, Beijnen JH, Schellens JH (2011) Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. doi: 10.1200/JCO.2010.33.1298
  18. 18.
    Buijs C, Mom CH, Willemse PH, Marike Boezen H, Maurer JM, Wymenga AN, de Jong RS, Nieboer P, de Vries EG, Mourits MJ (2009) Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study. Breast Cancer Res Treat 115(3):573–580. doi: 10.1007/s10549-008-0138-7 PubMedCrossRefGoogle Scholar
  19. 19.
    Loibl S, Schwedler K, von Minckwitz G, Strohmeier R, Mehta KM, Kaufmann M (2007) Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients—a double-blind, randomized study. Ann Oncol 18(4):689–693. doi: 10.1093/annonc/mdl478 PubMedCrossRefGoogle Scholar
  20. 20.
    Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, Ullmer L, Gallagher A, Cullen J, Gehan E, Hayes DF, Isaacs C (2005) Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 23(28):6919–6930. doi: 10.1200/JCO.2005.10.081 PubMedCrossRefGoogle Scholar
  21. 21.
    Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA, Halyard MY, Pruthi S, Novotny PJ, Rummans TA (2002) Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 20(6):1578–1583PubMedCrossRefGoogle Scholar
  22. 22.
    Wu MF, Hilsenbeck SG, Tham YL, Kramer R, Elledge RM, Chang JC, Friedman LC (2009) The efficacy of sertraline for controlling hot flashes in women with or at high risk of developing breast cancer. Breast Cancer Res Treat 118(2):369–375. doi: 10.1007/s10549-009-0425-y PubMedCrossRefGoogle Scholar
  23. 23.
    Kimmick GG, Lovato J, McQuellon R, Robinson E, Muss HB (2006) Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J 12(2):114–122. doi: 10.1111/j.1075-122X.2006.00218.x PubMedCrossRefGoogle Scholar
  24. 24.
    Barton DL, LaVasseur BI, Sloan JA, Stawis AN, Flynn KA, Dyar M, Johnson DB, Atherton PJ, Diekmann B, Loprinzi CL (2010) Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9. J Clin Oncol 28(20):3278–3283. doi: 10.1200/JCO.2009.26.6379 PubMedCrossRefGoogle Scholar
  25. 25.
    Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O (2007) Efficacy of citalopram on climacteric symptoms. Menopause 14(2):223–229. doi: 10.1097/01.gme.0000243571.55699.4a PubMedCrossRefGoogle Scholar
  26. 26.
    Pandya KJ, Raubertas RF, Flynn PJ, Hynes HE, Rosenbluth RJ, Kirshner JJ, Pierce HI, Dragalin V, Morrow GR (2000) 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 132(10):788–793PubMedGoogle Scholar
  27. 27.
    Bordeleau L, Pritchard KI, Loprinzi CL, Ennis M, Jugovic O, Warr D, Haq R, Goodwin PJ (2010) Multicenter, randomized, cross-over clinical trial of venlafaxine versus gabapentin for the management of hot flashes in breast cancer survivors. J Clin Oncol 28(35):5147–5152. doi: 10.1200/JCO.2010.29.9230 PubMedCrossRefGoogle Scholar
  28. 28.
    Biglia N, Sgandurra P, Peano E, Marenco D, Moggio G, Bounous V, Tomasi Cont N, Ponzone R, Sismondi P (2009) Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E. Climacteric 12(4):310–318. doi: 10.1080/13697130902736921 PubMedCrossRefGoogle Scholar
  29. 29.
    Loprinzi CL, Kugler JW, Barton DL, Dueck AC, Tschetter LK, Nelimark RA, Balcueva EP, Burger KN, Novotny PJ, Carlson MD, Duane SF, Corso SW, Johnson DB, Jaslowski AJ (2007) Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. J Clin Oncol 25(3):308–312. doi: 10.1200/JCO.2006.07.5390 PubMedCrossRefGoogle Scholar
  30. 30.
    Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, Sweeney TJ, Banerjee TK, Flynn PJ (2005) Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 366(9488):818–824. doi: 10.1016/S0140-6736(05)67215-7 PubMedCrossRefGoogle Scholar
  31. 31.
    Loprinzi CL, Qin R, Balcueva EP, Flynn KA, Rowland KM Jr, Graham DL, Erwin NK, Dakhil SR, Jurgens DJ, Burger KN (2010) Phase III, randomized, double-blind, placebo-controlled evaluation of pregabalin for alleviating hot flashes, N07C1. J Clin Oncol 28(4):641–647. doi: 10.1200/JCO.2009.24.5647 PubMedCrossRefGoogle Scholar
  32. 32.
    Pruthi S, Qin R, Terstreip SA, Liu H, Loprinzi CL, Shah TR, Tucker KF, Dakhil SR, Bury MJ, Carolla RL, Steen PD, Vuky J, Barton DL (2012) A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause 19(1):48–53Google Scholar
  33. 33.
    MacGregor CA, Canney PA, Patterson G, McDonald R, Paul J (2005) A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer 41(5):708–714. doi: 10.1016/j.ejca.2005.01.005 PubMedCrossRefGoogle Scholar
  34. 34.
    Nikander E, Kilkkinen A, Metsa-Heikkila M, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O (2003) A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol 101(6):1213–1220PubMedCrossRefGoogle Scholar
  35. 35.
    Van Patten CL, Olivotto IA, Chambers GK, Gelmon KA, Hislop TG, Templeton E, Wattie A, Prior JC (2002) Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 20(6):1449–1455PubMedCrossRefGoogle Scholar
  36. 36.
    Quella SK, Loprinzi CL, Barton DL, Knost JA, Sloan JA, LaVasseur BI, Swan D, Krupp KR, Miller KD, Novotny PJ (2000) Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: a North Central Cancer Treatment Group Trial. J Clin Oncol 18(5):1068–1074PubMedGoogle Scholar
  37. 37.
    Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, Barton DL, Sloan JA, Lavasseur BI, Rao RM, Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, Richelson E, Fauq AH (2006) Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1. J Clin Oncol 24(18):2836–2841. doi: 10.1200/JCO.2005.05.4296 PubMedCrossRefGoogle Scholar
  38. 38.
    Jacobson JS, Troxel AB, Evans J, Klaus L, Vahdat L, Kinne D, Lo KM, Moore A, Rosenman PJ, Kaufman EL, Neugut AI, Grann VR (2001) Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 19(10):2739–2745PubMedGoogle Scholar
  39. 39.
    Hernandez Munoz G, Pluchino S (2003) Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas 44(Suppl 1):S59–S65PubMedCrossRefGoogle Scholar
  40. 40.
    Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S (2009) Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 16(2):307–314. doi: 10.1097/gme.0b013e31818572a0 PubMedCrossRefGoogle Scholar
  41. 41.
    Loibl S, Lintermans A, Dieudonne AS, Neven P (2011) Management of menopausal symptoms in breast cancer patients. Maturitas 68(2):148–154. doi: 10.1016/j.maturitas.2010.11.013 PubMedCrossRefGoogle Scholar
  42. 42.
    Boutet G (2012) Management of hot flushes for breast cancer survivors. Gynecol Obstet Fertil 40(4):241–254. doi: 10.1016/j.gyobfe.2012.02.015 PubMedCrossRefGoogle Scholar
  43. 43.
    Clemons M, Clamp A, Anderson B (2002) Management of the menopause in cancer survivors. Cancer Treat Rev 28(6):321–333PubMedCrossRefGoogle Scholar
  44. 44.
    Desmarais JE, Looper KJ (2009) Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. J Clin Psychiatry 70(12):1688–1697. doi: 10.4088/JCP.08r04856blu PubMedCrossRefGoogle Scholar
  45. 45.
    Pal (2010) CYP2D6 testing falls short as predictor of adjuvant tamoxifen efficacy Accessed 30 janvier 2012
  46. 46.
    National Institute for Clinical Excellence (2009) Early and locally advanced breast cancer: diagnosis and treatment. National Collaborating Centre for CancerGoogle Scholar
  47. 47.
    National Comprehensive Cancer Network (2011) NCCN Guidelines Version 2.2011 Breast cancerGoogle Scholar
  48. 48.
    Hickey M, Saunders C, Partridge A, Santoro N, Joffe H, Stearns V (2008) Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer. Ann Oncol 19(10):1669–1680. doi: 10.1093/annonc/mdn353 PubMedCrossRefGoogle Scholar
  49. 49.
    Reid RL, Blake J, Abramson B, Khan A, Senikas V, Fortier M (2009) Menopause and osteoporosis update 2009. J Obstet Gynaecol Can 222:S1–S47Google Scholar
  50. 50.
    American Association of Clinical Endocrinologists (2006) Medical guidelines for clinical practice for the diagnostic and treatment of menopauseGoogle Scholar
  51. 51.
    Chang YC, Parker J, Dooley WC (2006) Hot flash therapies in breast cancer survivors. Support Cancer Ther 4(1):38–48. doi: 10.3816/SCT.2006.n.030 PubMedCrossRefGoogle Scholar
  52. 52.
    Tempfer CB, Froese G, Heinze G, Bentz EK, Hefler LA, Huber JC (2009) Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med 122(10):939–946. doi: 10.1016/j.amjmed.2009.04.018, e939PubMedCrossRefGoogle Scholar
  53. 53.
    Velentzis LS, Woodside JV, Cantwell MM, Leathem AJ, Keshtgar MR (2008) Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know. Eur J Cancer 44(13):1799–1806. doi: 10.1016/j.ejca.2008.05.019 PubMedCrossRefGoogle Scholar
  54. 54.
    Limer JL, Speirs V (2004) Phyto-oestrogens and breast cancer chemoprevention. Breast Cancer Res 6(3):119–127. doi: 10.1186/bcr781bcr781 PubMedCrossRefGoogle Scholar
  55. 55.
    Duffy C, Cyr M (2003) Phytoestrogens: potential benefits and implications for breast cancer survivors. J Womens Health (Larchmt) 12(7):617–631. doi: 10.1089/154099903322404276 CrossRefGoogle Scholar
  56. 56.
    Li J, Godecke T, Chen SN, Imai A, Lankin DC, Farnsworth NR, Pauli GF, van Breemen RB, Nikolic D (2011) In vitro metabolic interactions between black cohosh (Cimicifuga racemosa) and tamoxifen via inhibition of cytochromes P450 2D6 and 3A4. Xenobiotica. doi: 10.3109/00498254.2011.603385
  57. 57.
    Rostock M, Fischer J, Mumm A, Stammwitz U, Saller R, Bartsch HH (2011) Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints—a prospective observational study. Gynecol Endocrinol 27(10):844–848. doi: 10.3109/09513590.2010.538097 PubMedCrossRefGoogle Scholar
  58. 58.
    Al-Akoum M, Dodin S, Akoum A (2007) Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Can J Physiol Pharmacol 85(11):1153–1159. doi: 10.1139/Y07-111 PubMedCrossRefGoogle Scholar
  59. 59.
    Bodinet C, Freudenstein J (2002) Influence of Cimicifuga racemosa on the proliferation of estrogen receptor-positive human breast cancer cells. Breast Cancer Res Treat 76(1):1–10PubMedCrossRefGoogle Scholar
  60. 60.
    Borrelli F, Ernst E (2008) Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy. Pharmacol Res 58(1):8–14. doi: 10.1016/j.phrs.2008.05.008 PubMedCrossRefGoogle Scholar
  61. 61.
    Huntley A (2004) The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa). Expert Opin Drug Saf 3(6):615–623PubMedCrossRefGoogle Scholar
  62. 62.
    Collège des médecins du Québec et Ordre des pharmaciens du Québec (2004) Les produits de santé naturels: Pour mieux conseiller vos patients. document de référence 1–25Google Scholar
  63. 63.
    Cook DJ, Guyatt GH, Laupacis A, Sackett DL (1992) Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest 102(4 Suppl):305S–311SPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sylvain L’Espérance
    • 1
  • Suzanne Frenette
    • 2
    Email author
  • Anne Dionne
    • 3
  • Jean-Yves Dionne
    • 4
  • Comité de l’évolution des pratiques en oncologie (CEPO)
    • 5
  1. 1.Comité de l’évolution des pratiques en oncologieQuébecCanada
  2. 2.Department of PharmacyHôpital Maisonneuve-RosemontMontréalCanada
  3. 3.Department of PharmacyHôpital du St-Sacrement (CHU de Québec)QuébecCanada
  4. 4.Mont-RoyalCanada
  5. 5.Direction québécoise de cancérologieMinistère de la Santé et des Services sociaux du QuébecQuébecCanada

Personalised recommendations