Breast Cancer Research and Treatment

, Volume 173, Issue 3, pp 511–520 | Cite as

Quantitative comparison of drug efficacy in treating hot flashes in patients with breast cancer

  • Ting Li
  • Juan Yang
  • Yinghua Lv
  • Fang Yin
  • Ling Xu
  • Hongxia Liu
  • Qingshan ZhengEmail author
  • Lujin LiEmail author



This study aimed to quantitatively evaluate drug efficacy and identify relevant factors that affect the relief of hot flashes in patients with breast cancer.


A comprehensive literature search was performed using public databases. Randomized clinical studies on drug therapy for the treatment of hot flashes in patients with breast cancer were identified. A time-effect model was established, and crucial pharmacodynamic parameters, such as maximal efficacy (Emax) and onset time (ET50), were used to reflect the differences in efficacy among the drugs.


Eighteen studies involving 5178 subjects were included. It was found that the baseline of hot flashes was an important factor for the Emax value of drugs. After correcting the baseline to the level of eight times per day, the Emax values of progesterone, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs), neuroleptic agents, tibolone, phytoestrogen, other types of drugs, and placebo were 8.3(95%CI 6.8, 9.9),5.1(95%CI 4.4, 5.7), 4.4(95%CI 3.6, 5.3), 4.0(95%CI 3.6, 4.3), 3.4(95%CI 2.4, 4.3), 2.5(95%CI 0.8, 4.2), and 2.7(95%CI 2.1, 3.3), respectively. The ET50 of all the drugs were approximately 2–2.5 weeks, which was obviously longer than that of the placebo (1.2 weeks). When compared with the previously reported efficacy characteristics in natural menopausal women, no significant difference was found between the two populations.


Progesterone showed the highest efficacy, followed by SSRIs/SNRIs, neuroleptic agents, and tibolone, while phytoestrogen and other types of drugs showed no efficacy advantages. There is a significant association between the baseline of hot flashes and drug efficacy, while there was no significant difference between breast cancer patients and natural menopausal women.


Hot flashes Breast cancer Medication guidelines Model-based meta-analysis 


Author Contributions

T.L & J.Y selected studies and extracted the data, analyzed and interpreted the data, YH.L & F.Y wrote the manuscript, and revised the manuscript. HX.L and L.X contributed to data extraction and cleaning. LJ.L and QS.Z participated in conception and design of the work and revised the paper critically for important intellectual content. All authors read and approved the final manuscript. All authors have approved the final article.


This study was provided by the project of Shanghai Municipal Health Planning Commission (2018YQ48), Science and Technology Innovation Action Plan of Shanghai (17401970900) and National Major Scientific and Technological Special Project for ‘Significant New Drugs Development’ during the Thirteenth Five-year Plan Period (2018ZX09734005-001-002, 2018ZX09734005-006, 2018ZX09711001-009-001, 2018ZX09731016, 2017ZX09304003).

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors.

Supplementary material

10549_2018_5029_MOESM1_ESM.docx (761 kb)
Supplementary material 1 (DOCX 760 KB)


  1. 1.
    Harris PF, Remington PL, Trentham-Dietz A, Allen CI, Newcomb PA (2002) Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manag 23:501–509CrossRefGoogle Scholar
  2. 2.
    Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62CrossRefPubMedGoogle Scholar
  3. 3.
    Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107:167–180CrossRefPubMedGoogle Scholar
  4. 4.
    Lash TL, Fox MP, Westrup JL, Fink AK, Silliman RA (2006) Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat 99:215–220CrossRefPubMedGoogle Scholar
  5. 5.
    Chang HY, Jotwani AC, Lai YH, Jensen MP, Syrjala KL, Fann JR et al (2016) Hot flashes in breast cancer survivors: Frequency, severity and impact. Breast 27:116–121CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bordeleau L, Pritchard K, Goodwin P, Loprinzi C (2007) Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review. Clin Ther 29:230–241CrossRefPubMedGoogle Scholar
  7. 7.
    Leon-Ferre RA, Majithia N, Loprinzi CL (2017) Management of hot flashes in women with breast cancer receiving ovarian function suppression. Cancer Treat Rev 52:82–90CrossRefPubMedGoogle Scholar
  8. 8.
    Garrido Oyarzun MF, Castelo-Branco C (2017) Use of hormone therapy for menopausal symptoms and quality of life in breast cancer survivors. Safe ethical? Gynecol Endocrinol 33:10–15CrossRefPubMedGoogle Scholar
  9. 9.
    Hervik JB, Stub T (2016) 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 160:223–236CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Johns C, Seav SM, Dominick SA, Gorman JR, Li H, Natarajan L et al (2016) Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions. Breast Cancer Res Treat 156:415–426CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Loprinzi CL, Barton DL, Rhodes D (2001) Management of hot flashes in breast-cancer survivors. Lancet Oncol 2:199–204CrossRefPubMedGoogle Scholar
  12. 12.
    Gupta P, Sturdee DW, Palin SL, Majumder K, Fear R, Marshall T et al (2006) Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life. Climacteric 9:49–58CrossRefPubMedGoogle Scholar
  13. 13.
    Hunter MS, Grunfeld EA, Mittal S, Sikka P, Ramirez AJ, Fentiman I et al (2004) Menopausal symptoms in women with breast cancer: prevalence and treatment preferences. Psychooncology 13:769–778CrossRefPubMedGoogle Scholar
  14. 14.
    CHMP E (2005) Guideline on clinical investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in postmenopausal women. European Medicines Agency, LondonGoogle Scholar
  15. 15.
    Li L, Xu L, Wu J, Dong L, Zhao S, Zheng Q (2016) Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Eur J Clin Pharmacol 72:1051–1058CrossRefPubMedGoogle Scholar
  16. 16.
    Li L, Xu L, Wu J, Dong L, Lv Y, Zheng Q (2017) Quantitative analysis of placebo response and factors associated with menopausal hot flashes. Menopause 24:932–937CrossRefPubMedGoogle Scholar
  17. 17.
    Fenlon D, Morgan A, Khambaita P, Mistry P, Dunn J, Ah-See ML et al (2017) Management of hot flushes in UK breast cancer patients: clinician and patient perspectives. J Psychosom Obstetr Gynaecol 38:276–283CrossRefGoogle Scholar
  18. 18.
    Makubate B, Donnan PT, Dewar JA, Thompson AM, McCowan C (2013) Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer 108:1515–1524CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Santen RJ, Stuenkel CA, Davis SR, Pinkerton JV, Gompel A, Lumsden MA (2017) Managing menopausal symptoms and associated clinical issues in breast cancer survivors. J Clin Endocrinol Metab 102:3647–3661CrossRefPubMedGoogle Scholar
  20. 20.
    Joffe H, Partridge A, Giobbie-Hurder A, Li X, Habin K, Goss P et al (2010) Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. Menopause 17:908–916CrossRefPubMedGoogle Scholar
  21. 21.
    Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C et al (2005) Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 23:6919–6930CrossRefPubMedGoogle Scholar
  22. 22.
    Irarrazaval OM, Gaete GL (2016) [Antidepressants agents in breast cancer patients using tamoxifen: review of basic and clinical evidence]. Revista medica de Chile 144:1326–1335CrossRefGoogle Scholar
  23. 23.
    Boekhout AH, Vincent AD, Dalesio OB, van den Bosch J, Foekema-Tons JH, Adriaansz S et al (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 29:3862–3868CrossRefPubMedGoogle Scholar
  24. 24.
    Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P et al (2009) Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 10:135–146CrossRefPubMedGoogle Scholar
  25. 25.
    Bardia A, Novotny P, Sloan J, Barton D, Loprinzi C (2009) Efficacy of nonestrogenic hot flash therapies among women stratified by breast cancer history and tamoxifen use: a pooled analysis. Menopause 16:477–483CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center for Drug Clinical ResearchShanghai University of Traditional Chinese MedicineShanghaiChina

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