Suzanne Somers, Breast Cancer, and Hormone Therapy: A Reminder About the REAL Data

Recently, I learned that Suzanne Somers has a reoccurrence of her breast cancer, which was originally diagnosed in 2000. Through years of work and personal experiences, Suzanne Somers was instrumental in bringing forward a voice for women to better understand the role of hormones and their bodies, as well as the compounding pharmacy industry, which is vital for the delivery of safe and effective hormone replacement therapies. This is especially true, as women are the victims of extreme gender bias in medicine. Nothing is more evident of this bias than the fact that the commercial industry does not even have a single FDA-approved testosterone product for women, but so many for men that I have lost count.

As news of Ms. Somers reoccurrence spreads, I am 100% confident that many uneducated providers and laypersons are going to attack and blame the hormonal therapies she has taken over the years. This is due to the fact people still believe — based on the falsely reported Women’s Health Initiative Study —that all hormones cause breast cancer. Nothing could be further from the truth!

Let us review the evidence.

• After a close review of the original CEE plus MPA (Prempro) trial results from 2002, as well as subsequent publications for 2006 and 2010, they clearly demonstrate that the hazard ratio (HR) for breast cancer was not properly interpreted for provider or the patients they treat. The increased HR for breast cancer reported from this arm of the trial was not due to an increased incidence rate of breast cancer in the women randomized to Prempro therapy. Instead, it was due to a decreased incidence rate of breast cancer in the women randomized to the placebo group who used hormone therapy prior to randomization to the WHI trial; a previous use of hormones protected patients. Therefore, after decades of study, the preponderance of data showed a null effect on breast cancer when patients are treated with CEE plus MPA.

• Compared to women who received placebo, women in the WHI CEE (Premarin) trial showed a 21% (hazard ratio of 0.79, 95% confidence interval, 0.5-1.02) non-significant reduction in breast cancer after a median of 7.2 years of randomized treatment with 7 fewer breast cancer cases/10,000 women/year of CEE Premarin therapy. Among women who were taking their study pills and were at least 80% compliant with CEE therapy, breast cancer risk was statistically significantly reduced by 32% (HR 0.67; 95% CI, 90.47-0.97) relative to placebo. In addition, across all women regardless of compliance, ductal carcinoma was statistically significantly reduced by 29% (HR 0.71; 95% CI 0.52-0.99) by taking CEE therapy relative to placebo after 7.1 years of follow up.

• After 18 years for cumulative follow up of the WHI CEE cohort, breast cancer mortality was statistically significantly reduced by 45% (HR 0.55, CI 0.33-0.92). This may be the most overlooked finding of the WHI CEE trial. Even the endocrine-targeted agents (Tamoxifen, Raloxifene, aromatase inhibitors) do NOT reduce mortality from breast cancers. A woman’s risk of death from cardiovascular disease went up after 5 years of these agents, which is likely contributed to the lack of hormones, which are highly protective of the cardiovascular system.

• Testosterone is the most abundant hormone during a women’s reproductive lifetime, which is not fully appreciated by the medical community or community at large. Testosterone effects women in the same way as it does men. It aids in mood, energy, endurance and recovery, libido and sexual enhancement, cognition, bone health, glucose metabolism and insulin sensitivity, weight control, to name a few of its positive effects. Another very important role of testosterone is to protect the breast from developing breast cancer. Testosterone decreases inflammation, decreases proliferation/hyperplasia, increases ER-B which inhibits proliferation of the breast cells, increases cell death (Pro-apoptotic), and decreases invasive breast cancer cell growth.

• Testosterone pellets have been used to treat testosterone deficiency in women since 1937. Additionally, testosterone pellets have been used to treat invasive breast cancer. There is mounting evidence to support the use of testosterone (pellets in particular) to lower breast cancer risk, as well as reoccurrence rates in women who have breast cancer; all the while dramatically improving a patient’s quality of life while undergoing treatment for breast cancer.

• Breast cancer risk is often multifactorial and women who are not on hormones still develop breast cancer, and in fact, those patients often have worse outcomes. Risk factors for developing breast cancer include (but not limited to): age, obesity, sedentary lifestyle, alcohol use/abuse, being a flight attendant, BRCA 1 and 2 mutations, family history, dense breasts etc.

After two decades from the release of the WHI dataset, it is alarming that the conventional thinking has not evolved to support the truth. This lack of evolution, only creates confusion and harms the overall health of female patients. My only hope is that Suzanne Somers’ voice in support of hormones isn’t drowned out by her current diagnosis and the likely onslaught of naysayers. Suzanne would not want her voice and message to be in vain. She is a fighter, and I know she will not only survive this, but thrive through adversity as she always does.

Angela DeRosa, DO, MBA, CPE

Founder/CEO of the Hormonal Health Institute

Medical Director, Belmar Pharma Solutions

References:

1. The Womens’ Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The Women’s Health Initiative randomized controlled trail. JAMA 2004; 291-1701-12

2. Hodis HN et al. Climateric 2018; 21 (6); 521-528

3. R. Chlebowski et al. “Breast Cancer Prevention: Time for Change” JCO Oncology Practice, Volume 17, Issue 12 page 709-716

4. Hickey, T. E., Robinson, J. L. L., & Carroll J. S. (2012). Minireview: the androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene. Mol Endocrinol, 26(8)1252-67.

5. ROBERT M. BRYAN, FRCS, RONALD J. MERCER, FRACS, RICHARD C. BENNETT, MS, GEORGE C. RENNIE, MA, TAT H. LIE, BAPPSC, FRANCIS J. MORGAN, MD: Androgen Receptors in Breast Cancer. Cancer 54:2436-2440, 1984

6. Rika Fujii, Toru Hanamura, Takashi Suzuki c, Tatsuyuki Gohno, Yukiko Shibahara, Toshifumi Niwa, Yuri Yamaguchii, Koji Ohnuki g, Yoichiro Kakugawa, Hisashi Hirakawa, Takanori Ishida, Hironobu Sasano, Noriaki Ohuchi, Shin-ichi Hayashi: Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. 2014 Elsevier

7. Sijie Li, Bing Han, Guojin Liu, Songyun Li, Johanne Ouellet, Fernand Labrie, and Georges Pelletier: Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland. Volume 58(6): 509–515, 2010 Journal of Histochemistry & Cytochemistry

8. Keely M. McNamara and Hironobu Sasano: Androgen and breast cancer: an update. Curr Opin Endocrinol Diabetes Obes 2016, 23:249–256

9. Mirco Pistelli, Miriam Caramanti , Tommasina Biscotti, Alfredo Santinelli, Alessandra Pagliacci, Mariagrazia De Lisa, Zelmira Ballatore, Francesca Ridolfi, Elena Maccaroni, Raffaella Bracci, Rossana Berardi, Nicola Battelli and Stefano Cascinu: Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations. Cancers 2014, 6, 1351-1362

10. Tracy Proverbs-Singh, Jarett L Feldman, Michael J Morris, Karen A Autio and Tiffany A Traina: Targeting the androgen receptor in prostate and breast cancer several new agents in development. Endocrine-Related Cancer (2015) 22, R87–R106

11. Timothy R. Rebbeck, Philip W. Kantoff, Krishna Krithivas, Susan Neuhausen, M. Anne Blackwood, Andrew K. Godwin, Mary B. Daly, Steven A. Narod, Judy E. Garber, Henry T. Lynch,8 Barbara L. Weber, Myles Brown: Modification of BRCA1-Associated Breast Cancer Risk by the Polymorphic Androgen-Receptor CAG Repeat. Am. J. Hum. Genet. 64:1371–1377, 1999

12. A. Thakkar, B. Wang, M. Picon-Ruiz, P. Buchwald, Tan A. Ince: Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer. Breast Cancer Res Treat (2016) 157: 77

13. Isabell Witzel • Monika Graeser • Thomas Karn • Markus Schmidt •Ralph Wirtz • Dina Schutze • Alma Rausch • Fritz Ja¨nicke •Karin Milde-Langosch • Volkmar Muller: Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers. J Cancer Res Clin Oncol (2013) 139:809–816

14. Dimitrakakis C, Zhou J, Bondy CA. Androgens and mammary growth and neoplasia. Fertil Steril 2002

15. Frasor J, Stossi F, Danes JM, Komm B, Lyttle CR, Katzenellenbogen BS.Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res 2004

16. Somboonporn W, Davis SR. Testosterone effects on the breast: implications for testosterone therapy for women. Endocr Rev 2004

17. Yeh S, Hu YC, Wang PH, Xie C, Xu Q, Tsai MY, Dong Z, Wang RS, Lee TH, Chang C. Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J Exp Med 2003

18. J.F. Forbes, J. Cuzick, A. Buzdar, A. Howell, J.S. Tobias, M. Baum, et al., Effect of anastrozole and tamoxifen as adjuvant treatment for early- stage breast cancer: 100-month analysis of the ATAC trial, Lancet Oncol. 2008

19. H. Mouridsen, A. Giobbie-Hurder, A. Goldhirsch, B. Thürlimann, R. Paridaens, I. Smith, et al., Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer, New Engl. J. Med. 2009

20. S. Masamura, S.J. Santner, D.F. Heitjan, R.J. Santen, Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells, J. Clin. Endocrinol. Metab. 1995

21. R. Santen, M.H. Jeng, J.P. Wang, R. Song, S. Masamura, R. McPherson, et al., Adaptive hypersensitivity to estradiol: potential mechanism for secondary hormonal responses in breast cancer patients, J. Steroid Biochem. Mol. Biol. 2001

22. T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, et al., Sex steroid- producing enzymes in human breast cancer, Endocr. Relat. Cancer 2005

23. F.E. Vera-Badillo, A.J. Templeton, P. de Gouveia, I. Diaz-Padilla, P.L. Bedard, M. Al-Mubarak, et al., Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis, J. Natl. Cancer Inst. 2014

24. M. Ni, Y. Chen, E. Lim, H. Wimberly, S.T. Bailey, Y. Imai, et al., Targeting androgen receptor in estrogen receptor-negative breast cancer, Cancer Cell 2011

25. T.E. Hickey, J.L. Robinson, J.S. Carroll, Tilley W.D. Minireview, The androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene, Mol. Endocrinol. 2012

26. T. Suzuki, Y. Miki, T. Moriya, J. Akahira, T. Ishida, H. Hirakawa, et al., 5Alphareductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production, Int. J. Cancer, 2007

27. K. Takagi, Y. Miki, S. Nagasaki, H. Hirakawa, Y. Onodera, J. Akahira, et al., Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment, Endocr. Relat. Cancer, 2010

28. Y. Yamaguchi, H. Takei, K. Suemasu, Y. Kobayashi, M. Kurosumi, N. Harada, et al., Tumor-stromal interaction through the estrogen-signaling pathway in human breast cancer, Cancer Res. 2005

29. P. Kabos, J. Finlay- Schultz, C. Li, E. Kline, C. Finlayson, J. Wisell, et al., Patient-derived luminal breast cancer xenografts retain hormone receptor heteroge- neity and help define unique estrogen-dependent gene signatures, Breast Cancer Res. Treat. 2012

30. G. Bogina, L. Bortesi, M. Marconi, M. Venturini, G. Lunardi, F. Coati, et al., Comparison of hormonal receptor and HER-2 status between breast primary tumours and relapsing tumours: clinical implications of progesterone receptor loss, Virchows Arch. 2011

31. S.N. Birrell, J.M. Bentel, T.E. Hickey, C. Ricciardelli, M.A. Weger, D.J. Horsfall, et al., Androgens induce divergent proliferative responses in human breast cancer cell lines, J. Steroid Biochem. Mol. Biol. 1995

32. Dimitrakakis, C. 2011. Androgens and breast cancer in men and women. Endocrinology and metabolism clinics of North America. 40, 3, 533-547.

33. Glaser, R. L., & Dimitrakakis, C. (2014). Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer. Menopause (New York, NY), 21(6), 673.

34. Glaser, R. L., York, A. E., & Dimitrakakis, C. (2017). Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications. Menopause, 24(7), 859-864.

35. Glaser, R. L., York, A. E., & Dimitrakakis, C. (2014). Efficacy of subcutaneous testosterone on menopausal symptoms in breast cancer survivors. J Clin Oncol.

36. Glaser, R.L, & Dimitrakakis, C (2013 ) Reduced breast cancer incidence in women treated with subcutaneous testosterone or testosterone with anastrozole: A prospective, observational study. Maturitas