Skip to main content

Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial

Supportive Care in Cancer volume 27, pages 1879–1889 (2019)Cite this article

Abstract

Purpose

Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF).

Methods

In this multicenter randomized double-blind placebo-controlled phase III study (ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization.

Results

Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, − 2.9; P, − 2.5 points, p = 0.756) and relative decrease (A, − 17%; P, − 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470).

Conclusions

The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

ET:

Endocrine therapy

QoL:

Quality of life

HF:

Hot flushes.

HFS:

HF score

HFRDIS:

Hot Flash Related Daily Interference Scale

References

  1. Hammond ME (2010) Commentary: improving breast cancer testing for patients-the secret sauce is collaboration. J Oncol Pract 6:198

    Article  PubMed  PubMed Central  Google Scholar 

  2. Guastalla JP (2005) Hormonothérapie adjuvante après la ménopause : dogmes et doutes. 27es journées de la SFSPM. Deauville:469–490

  3. Jones SE, Cantrell J, Vukelja S, Pippen J, O'Shaughnessy J, Blum JL, Brooks R, Hartung NL, Negron AG, Richards DA, Rivera R, Holmes FA, Chittoor S, Whittaker TL, Bordelon JH, Ketchel SJ, Davis JC, Ilegbodu D, Kochis J, Asmar L (2007) Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: report of a tamoxifen Exemestane adjuvant multicenter trial substudy. J Clin Oncol 25:4765–4771

    Article  CAS  PubMed  Google Scholar 

  4. Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  PubMed  Google Scholar 

  5. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, Kwan M, Gomez SL, Neugut AI (2011) Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat 126:529–537

    Article  CAS  PubMed  Google Scholar 

  6. Morgan A, Fenlon DR (2013) Is it me or is it hot in here? A plea for more research into hot flushes. Clin Oncol (R Coll Radiol) 25:681–683

    Article  CAS  Google Scholar 

  7. Complementary, Alternative, or Integrative Health: What’s In a Name? https://nccih.nih.gov/health/integrative-health Accessed 09 Aug 2018

  8. Arthur K, Belliard JC, Hardin SB, Knecht K, Chen CS, Montgomery S (2013) Reasons to use and disclose use of complementary medicine use - an insight from cancer patients. Cancer Clin Oncol 2:81–92

    PubMed  PubMed Central  Google Scholar 

  9. Arthur K, Belliard JC, Hardin SB, Knecht K, Chen CS, Montgomery S (2012) Practices, attitudes, and beliefs associated with complementary and alternative medicine (CAM) use among cancer patients. Integr Cancer Ther 11:232–242

    Article  PubMed  Google Scholar 

  10. Mao JJ, Palmer CS, Healy KE, Desai K, Amsterdam J (2011) Complementary and alternative medicine use among cancer survivors: a population-based study. J Cancer Surviv 5:8–17

    Article  PubMed  Google Scholar 

  11. Demarque D, Jouanny J, Poitevin B, et al. (2003) Pharmacologie et matière médicale homéopathique. In Editions CEDH (Centre d’Enseignement et de Développement de l’Homéopathie), 3rd Edition Paris, eds

  12. Bordet MF, Colas A, Marijnen P, Masson J, Trichard M (2008) Treating hot flushes in menopausal women with homeopathic treatment--results of an observational study. Homeopathy 97:10–15

    Article  CAS  PubMed  Google Scholar 

  13. Colau JC, Vincent S, Marijnen P, Allaert FA (2012) Efficacy of a non-hormonal treatment, BRN-01, on menopausal hot flushes: a multicenter, randomized, double-blind, placebo-controlled trial. Drugs R D 12:107–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sloan JA, Loprinzi CL, Novotny PJ, Barton DL, LaVasseur BI, Windschitl H (2001) Methodologic lessons learned from hot flash studies. J Clin Oncol 19:4280–4290

    Article  CAS  PubMed  Google Scholar 

  15. Carpenter JS (2001) The hot flash related daily interference scale: a tool for assessing the impact of hot flushes on quality of life following breast cancer. J Pain Symptom Manag 22(6):979–989

  16. Chien TJ, Hsu CH, Liu CY, Fang CJ (2017) Effect of acupuncture on hot flush and menopause symptoms in breast cancer- a systematic review and meta-analysis. PLoS One 12(8):e0180918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Spathis A, Fife K, Blackhall F, Bahadori R, Wharton R et al (2014) Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. J Clin Oncol 32:1882–1888

    Article  CAS  PubMed  Google Scholar 

  18. Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ (2010) Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 363:733–742

    Article  CAS  PubMed  Google Scholar 

  19. Denis F, Yossi S, Septans AL, Charron A, Voog E, Dupuis O et al (2015) Improving survival in patients treated for a lung cancer using self-evaluated symptoms reported through a web application. Am J Clin Oncol 40(5):464–469

  20. Mathie RT (2015) Controlled clinical studies of homeopathy. Homeopathy 104:328–332

    Article  PubMed  Google Scholar 

  21. Mathie RT, Wassenhoven MV, Jacobs J, Oberbaum M, Frye J, Manchanda RK, Roniger H, Dantas F, Legg LA, Clausen J, Moss S, Davidson JRT, Lloyd SM, Ford I, Fisher P (2016) Model validity and risk of bias in randomized placebo-controlled trials of individualised homeopathic treatment. Complement Ther Med 25:120–125

    Article  PubMed  Google Scholar 

  22. Bann CM, Sirois FM, Walsh EG (2010) Provider support in complementary and alternative medicine: exploring the role of patient empowerment. J Altern Complement Med 16:745–752

    Article  PubMed  Google Scholar 

  23. Pérol D, Provençal J, Hardy-Bessard AC, Coeffic D, Jacquin JP, Agostini C, Bachelot T, Guastalla JP, Pivot X, Martin JP, Bajard A, Ray-Coquard I (2012 Dec 17) Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial. BMC Cancer 12:603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the patients, staff at each study site, and all active investigators for their participation in the study (Online resource 1). We thank Sophie Darnis for medical editorial assistance with this report.

Funding

Laboratoires Boiron provided the study drug Actheane® and its matching placebo, and funds to the sponsor to conduct this study. Laboratoires Boiron had no role in study design, data collection, data analysis, data interpretation, nor writing of the report.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex 08, France

    Pierre-Etienne Heudel, Jean-Paul Guastalla & David Pérol

  2. Centre Léon Bérard, 28 rue Laennec, 69008, Lyon, France

    Pierre-Etienne Heudel

  3. Centre Jean Perrin, 58, Rue Montalembert, 63011, Clermont-Ferrand, France

    Isabelle Van Praagh-Doreau

  4. Centre Hospitalier, 3 Rue Adhémar, 26200, Montélimar, France

    Bernard Duvert

  5. Centre Hospitalier, BP1125, 73011, Chambéry, France

    Isabelle Cauvin

  6. Clinique Armoricaine de Radiologie, 21 rue du Vieux Séminaire, 22000, Saint Brieuc, France

    Anne-Claire Hardy-Bessard

  7. Institut de Cancérologie Lucien Neuwirth, 108, avenue Albert-Raimond, 42270, Saint-Priest-en-Jarez, France

    Jean-Philippe Jacquin

  8. Centre hospitalier de la région d’Annecy, 1 avenue de l’hôpital, BP90074, 74374, Annecy, France

    Laetitia Stefani

  9. Centre hospitalier de Roanne, 28, Rue de Charlieu, 42300, Roanne, France

    Lionel Vincent

  10. Centre hospitalier, 179, Boulevard Maréchal Juin, 26000, Valence, France

    Dominique Dramais

  11. Department of Clinical Research and Innovation, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex 08, France

    Ellen Blanc, Aurélie Belleville & Emilie Lavergne

Authors
  1. Pierre-Etienne Heudel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabelle Van Praagh-Doreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard Duvert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Isabelle Cauvin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne-Claire Hardy-Bessard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean-Philippe Jacquin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laetitia Stefani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lionel Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dominique Dramais
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jean-Paul Guastalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ellen Blanc
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Aurélie Belleville
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Emilie Lavergne
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. David Pérol
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PEH, JPG, DP contributed to the trial conception and design. PEH, IVPD, BV, IC, ACHB, JPJ, LS, LV, DD, and JPG contributed to data collection. EL did the statistical analysis and contributed together with EB, PEH, JPG, and DP to data analysis and interpretation. AB and EB were involved in quality control of data and algorithms. PEH, JPG, and DP supervised the study. All authors reviewed the report for intellectual content, provided comments, and gave final approval for publication.

Corresponding author

Correspondence to Pierre-Etienne Heudel.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

An informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Online resource 1

(DOCX 21 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Heudel, PE., Van Praagh-Doreau, I., Duvert, B. et al. Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial. Support Care Cancer 27, 1879–1889 (2019). https://doi.org/10.1007/s00520-018-4449-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-018-4449-x

Keywords

  • Early breast cancer
  • Hot flushes
  • Homeopathy
  • Quality of life