Evaluation of Homeopathic Treatment for Hot Flashes in Non Metastatic Breast Cancer (HBC)

• Evaluation of BRN01 efficacy in reducing the hot flash score after 8 weeks of treatment [ Time Frame: The patients are instructed to record the number and intensity of hot flashes in a self-evaluation booklet every day during the 2nd week of the first period (run-in period) and during the 8th week of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]

  Treatment efficacy scores will be calculated as follows: (hot flash score on the 8th week of the second period)-(hot flash score on the 2nd week of the first period).

  Then efficiency scores will be compared between the 2 arms (placebo versus BRN01).

• Evaluation of the mean daily intensity of hot flashes during the run-in period and on the 4th and 8th weeks of treatment in both arms. [ Time Frame: The patients are instructed to record the intensity of hot flashes in a self-evaluation booklet, daily, during the 2nd week of the first period (run-in period), and during the 4th and 8th weeks of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]
• Evaluation of the mean daily frequency of hot flashes during the run-in period and on the 4th and 8th weeks of treatment in both arms. [ Time Frame: The patients are instructed to record the number of hot flashes in a self-evaluation booklet, daily, during the 2nd week of the first period (run-in period), and during the 4th and 8th weeks of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]
• Evaluation of quality of life in both arms [ Time Frame: The patients are instructed to complete quality of life items on the 7th day of each evaluation period (2nd week of the run-in period, 4th and 8th weeks of the second period) ] [ Designated as safety issue: No ]
• Evaluation of patient satisfaction with the treatment and with the management of hot flashes. [ Time Frame: The patients are instructed to record all new hot flash treatments started, as well as their satisfaction with their management, on the 7th day of each evaluation period (2nd week of the run-in period, 4th and 8th weeks of the second period). ] [ Designated as safety issue: No ]
• Evaluation of treatment tolerance [ Time Frame: Side effects are registered by the oncologist at each visit (planned during the 3rd week or the 4th week of the run-in period and during the 9th week or the 10th week of the second period) ] [ Designated as safety issue: No ]
• Evaluation of patient compliance [ Time Frame: The number of remaining tablets will be counted at each visit (planned during the 3rd week or the 4th week of the run-in period and during the 9th week or the 10th week of the second period) ] [ Designated as safety issue: No ]

• Evaluation of BRN01 efficacy in reducing the hot flash score after 8 weeks of treatment [ Time Frame: The patients are instructed to record the number and intensity of hot flashes in a self-evaluation booklet every day during the 2nd week of the first period (run-in period) and during the 8th week of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]

  Treatment efficacy scores will be calculated as follows: (hot flash score on the 8th week of the second period)-(hot flash score on the 2nd week of the first period).

  Then efficiency scores will be compared between the 2 arms (placebo versus BRN01).

• Evaluation of the mean daily intensity of hot flashes during the run-in period and on the 4th and 8th weeks of treatment in both arms. [ Time Frame: The patients are instructed to record the intensity of hot flashes in a self-evaluation booklet, daily, during the 2nd week of the first period (run-in period), and during the 4th and 8th weeks of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]
• Evaluation of the mean daily frequency of hot flashes during the run-in period and on the 4th and 8th weeks of treatment in both arms. [ Time Frame: The patients are instructed to record the number of hot flashes in a self-evaluation booklet, daily, during the 2nd week of the first period (run-in period), and during the 4th and 8th weeks of the second period (placebo or BRN01). ] [ Designated as safety issue: No ]
• Evaluation of quality of life in both arms [ Time Frame: The patients are instructed to complete quality of life items on the 7th day of each evaluation period (2nd week of the run-in period, 4th and 8th weeks of the second period) ] [ Designated as safety issue: No ]
• Evaluation of patient satisfaction with the treatment and with the management of hot flashes. [ Time Frame: The patients are instructed to record all new hot flash treatments started, as well as their satisfaction with their management, on the 7th day of each evaluation period. ] [ Designated as safety issue: No ]
• Evaluation of treatment tolerance [ Time Frame: Side effects are registered by the oncologist at the end of the run-in period (the 3rd week or the 4th week after the inclusion) and at the end of the 2nd period (placebo or BRN01-the 9th week or the 10th week after the randomization) ] [ Designated as safety issue: No ]
• Evaluation of patient compliance [ Time Frame: The number of remaining tablets will be counted at the end of the run-in period (the 3rd week or the 4th week after the inclusion) and at the end of the second period (placebo or BRN01-the 9th week or the 10th week after the randomization). ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the efficacy of a homeopathic treatment (BRN01) in reducing hot flash scores after 4 weeks of treatment.

Chemotherapy is used as an adjuvant treatment for breast cancer, like hormone therapy in patients with hormone-sensitive breast cancer or immunotherapy in those with Human Epidermal growth factor Receptor 2 (HER2)-overexpressing cancer.

These adjuvant treatments reduce the risk of recurrence and metastasis. The side effects of hormone therapy are known and depend on the therapeutic strategy and the drugs used. The side effects of Tamoxifen are similar to menopausal symptoms: hot flashes (half of the female population), vaginal dryness or leukorrhea, nausea, irregular menstruation, benign ovarian cyst and, less frequently, weight gain. Aromatase inhibitors have the same side effects, though with lesser frequency and intensity. The incidence rate of hot flashes after adjuvant treatment in menopausal women with localized breast cancer is 60 to 65 %, and these reactions are very severe in one third of these women. Despite this fact, the management of hot flashes is not systematic and there is currently no therapeutic strategy with proven efficiency. BRN01 (Boiron laboratory) is a homeopathic remedy whose active ingredient is already present in other homeopathic drugs indicated for the management of menopausal hot flashes. BRN01 could reduce the intensity of the reaction in women with breast cancer receiving adjuvant hormonal treatment.

• Drug: BRN01
  2 tablets every morning and every evening during 8 to 10 weeks. Each patient will receive 1 set of 5 treatment boxes (60 tablets/box).
• Drug: Placebo
  2 tablets every morning and every evening during 8 to 10 weeks. Each patient will receive 1 set of 5 treatment boxes (60 tablets/box).

• Experimental: BRN01

  A 2 to 4 weeks run-in period is planned, during which all patients receive single blinded "hot flash evaluation treatment" which is actually a placebo (2 tablets every morning and every evening during 2 to 4 weeks). At the end of this period, the hot flash score is calculated. If the score is ≥10, the patient can be randomized to one of the 2 arms:

  • Experimental: BRN01
  • Placebo Comparator: Placebo
  Intervention: Drug: BRN01
• Placebo Comparator: Placebo

  A 2 to 4 weeks run-in period is planned, during which all patients receive single blinded "hot flash evaluation treatment" which is actually a placebo (2 tablets every morning and every evening during 2 to 4 weeks). At the end of this period, the hot flash score is calculated. If the score is ≥10, the patient can be randomized to one of the 2 arms:

  • Experimental: BRN01
  • Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Remontet L, Estève J, Bouvier AM, Grosclaude P, Launoy G, Menegoz F, Exbrayat C, Tretare B, Carli PM, Guizard AV, Troussard X, Bercelli P, Colonna M, Halna JM, Hedelin G, Macé-Lesec'h J, Peng J, Buemi A, Velten M, Jougla E, Arveux P, Le Bodic L, Michel E, Sauvage M, Schvartz C, Faivre J. Cancer incidence and mortality in France over the period 1978-2000. Rev Epidemiol Sante Publique. 2003 Feb;51(1 Pt 1):3-30.
• Ménégoz F, Black RJ, Arveux P, Magne V, Ferlay J, Buémi A, Carli PM, Chapelain G, Faivre J, Gignoux M, Grosclaude P, Mace-Lesec'h J, Raverdy N, Schaffer P. Cancer incidence and mortality in France in 1975-95. Eur J Cancer Prev. 1997 Oct;6(5):442-66.
• Coleman MP. Trends in breast cancer incidence, survival, and mortality. Lancet. 2000 Aug 12;356(9229):590-1; author reply 593. No abstract available. Erratum in: Lancet 2000 Aug 26;356(9231):774.
• Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardly A, Price KN, Goldhirsch A; Breast International Group (BIG) 1-98 Collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57.
• Finck G, Barton DL, Loprinzi CL, Quella SK, Sloan JA. Definitions of hot flashes in breast cancer survivors. J Pain Symptom Manage. 1998 Nov;16(5):327-33.
• Stearns V, Ullmer L, López JF, Smith Y, Isaacs C, Hayes D. Hot flushes. Lancet. 2002 Dec 7;360(9348):1851-61. Review.
• Couzi RJ, Helzlsouer KJ, Fetting JH. Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol. 1995 Nov;13(11):2737-44.
• Fellowes D, Fallowfield LJ, Saunders CM, Houghton J. Tolerability of hormone therapies for breast cancer: how informative are documented symptom profiles in medical notes for 'well-tolerated' treatments? Breast Cancer Res Treat. 2001 Mar;66(1):73-81.
• Lower EE, Blau R, Gazder P, Tummala R. The risk of premature menopause induced by chemotherapy for early breast cancer. J Womens Health Gend Based Med. 1999 Sep;8(7):949-54.
• McPhail G, Smith LN. Acute menopause symptoms during adjuvant systemic treatment for breast cancer: a case-control study. Cancer Nurs. 2000 Dec;23(6):430-43.
• Loprinzi CL, Zahasky KM, Sloan JA, Novotny PJ, Quella SK. Tamoxifen-induced hot flashes. Clin Breast Cancer. 2000 Apr;1(1):52-6.
• Love RR, Cameron L, Connell BL, Leventhal H. Symptoms associated with tamoxifen treatment in postmenopausal women. Arch Intern Med. 1991 Sep;151(9):1842-7.
• Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, Jonas WB. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997 Sep 20;350(9081):834-43. Erratum in: Lancet 1998 Jan 17;351(9097):220.
• Jonas WB, Kaptchuk TJ, Linde K. A critical overview of homeopathy. Ann Intern Med. 2003 Mar 4;138(5):393-9. Review.
• Cucherat M, Haugh MC, Gooch M, Boissel JP. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic Medicines Research Advisory Group. Eur J Clin Pharmacol. 2000 Apr;56(1):27-33.
• Jonas WB. Researching alternative medicine. Nat Med. 1997 Aug;3(8):824-7. No abstract available.
• Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA. 1993 Dec 1;270(21):2598-601. No abstract available.
• Grol R, Grimshaw J. Evidence-based implementation of evidence-based medicine. Jt Comm J Qual Improv. 1999 Oct;25(10):503-13.
• Barnes J, Ernst E. Complementary medicine. Br J Gen Pract. 1997 May;47(418):329. No abstract available.
• Clover A, Ratsey D. Homeopathic treatment of hot flushes: a pilot study. Homeopathy. 2002 Apr;91(2):75-9.
• Thompson EA, Reilly D. The homeopathic approach to the treatment of symptoms of oestrogen withdrawal in breast cancer patients. A prospective observational study. Homeopathy. 2003 Jul;92(3):131-4.
• Thompson EA, Montgomery A, Douglas D, Reilly D. A pilot, randomized, double-blinded, placebo-controlled trial of individualized homeopathy for symptoms of estrogen withdrawal in breast-cancer survivors. J Altern Complement Med. 2005 Feb;11(1):13-20.
• Relton C, Weatherley-Jones E. Homeopathy service in a National Health Service community menopause clinic: audit of clinical outcomes. J Br Menopause Soc. 2005 Jun;11(2):72-3.
• Bordet MF, Colas A, Marijnen P, Masson J, Trichard M. Treating hot flushes in menopausal women with homeopathic treatment--results of an observational study. Homeopathy. 2008 Jan;97(1):10-5.
• Sloan JA, Loprinzi CL, Novotny PJ, Barton DL, Lavasseur BI, Windschitl H. Methodologic lessons learned from hot flash studies. J Clin Oncol. 2001 Dec 1;19(23):4280-90.

Inclusion Criteria:

• Female patient aged ≥ 18 years
• Women with histologically proven non metastatic breast cancer
• ECOG PS ≤ 1
• Patient receiving adjuvant hormonal therapy for at least 1 month (aromatase inhibitor or Tamoxifen ± ovarian function suppression (Luteinizing Hormone Releasing Hormone agonist (LH-RH agonist), ovariectomy...))
• Patient complaining of hot flashes with moderate to severe intensity, affecting quality of life, for at least 1 month before inclusion
• Patient agreement not to start another hot flash treatment during the study (allopathic treatment, E vitamin, dietary supplement, phytotherapy, acupuncture...)
• Patient able to understand, read and write French
• Mandatory affiliation with a health insurance system
• Signed, written informed consent

Exclusion Criteria:

• Ongoing chemotherapy or radiotherapy, or treatment planned to begin during the study
• Patient with a condition known to induce hot flashes such as hyperthyroidism, diabetes, adrenal tumor, enteric carcinoid tumor, mastocytosis...
• Patient with severe renal failure, severe hepatic failure, or cardiovascular disease

• Patient with one of the following contraindications:

  • known hypersensitivity to one of the components of the study drug
  • galactose, fructose intolerance
  • Lapp lactase deficiency, isomaltase invertase deficiency
  • Glucose or galactose malabsorption syndrome
• Follow up impossible because of social, familial, geographical or psychological reasons
• Patient suspected of poor compliance with protocol or treatment
• Participation in another biomedical research trial in the same indication, or administration of an experimental drug in the same indication in the 30 days before inclusion