85% of cancers occur in women with no family history of breast cancer.  The major risk factors remain gender and age.  The incidence of breast cancer is decreasing, likely due to increased screening, as well as decreased use of synthetic hormone replacement.

The hormones we produce naturally (estradiol, progesterone, and testosterone) each have unique chemical structures. They join with their respective receptors or “gates” on the cell membrane, like a key into a lock, and instruct our cells how to function.  Synthetic hormones have different chemical structures than our natural hormones and cannot join to receptors properly.  Negative effects often result.  The hormones used in the Women’s Health Initiative Study, Premarin and Provera (both synthetic) increased the risk of breast cancer by 29%.  The increase may have been largely due to Provera which blocks up to 80-95% of the testosterone receptors.  Natural or bioidentical  testosterone is actually protective to the breast so it doesn’t help to block testosterone receptors! (Bioidentical testosterone has the same exact chemical structure, as the testosterone that the body produces naturally).  Progesterone is also protective to the breast in women that do not carry the BRCA mutations.  Provera of course also blocks the progesterone receptor.  See Dr. Edward Friedman’s book “The New Testosterone Treatment- How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer, and Alzheimer’s”  2013.

Agnes Fournier et al, in 2008, published a study (in Breast Cancer Research and Treatment) entitled “Unequal risks for breast cancer associated with different hormone replacement therapies…”.  The use of bioidentical estradiol with bioidentical progesterone did not increase breast cancer risk, however the risk did increase with the use of synthetic progestins (synthetic progesterone type hormones) up to 69%.  Estradiol alone, in this study, increased the risk by 28%.

C. Dimitrakakis et al, followed a group of 508 Australian women who were placed on bioidentical testosterone pellets, in addition, to their standard estrogen/progestin hormone replacement therapy for complaints of emotional lability, decreased energy, decreased focus, and decreased libido. (The estrogens used in this study were either oral conjugated estrogens (like Premarin) or estradiol pellets; the progestins were either medroxyprogesterone acetate (Provera) or norethisterone).

The breast cancer cases, reported as “cases per 100,000 person-years” (p-y) were as follows:

Estradiol and Testosterone Group- 115/100,000 p-y

Estradiol, Progestin, and Testosterone Group-  293/100,000 p-y

Estradiol/Testosterone and Estradiol/Progestin/Testosterone -238/100,000 p-y

In the Women’s Health Initiative Study, the risk on Premarin/Provera was 380/100,000 p-y; in the Million Women Study the risk on estrogen/progestagen (progesterone and progestins), the risk was 521/100,000 p-y.  The breast cancer cases for no hormone replacement therapy- 283/100,000 p-y.

There were less cases with the Estradiol/Testosterone group and the Combined Estradiol/Testosterone and Estradiol/Progestin/Testosterone group than there was for the no hormone replacement group!

Testosterone is known to protect cells in the breast from excessive estrogen stimulation.  Testosterone performs multiple actions on the testosterone receptor in the breast to decrease the formation of abnormal cells, prevent their division, and to promote cell death (a process known as Apoptosis).  For example, testosterone decreases the number and activity of estrogen receptor (ER) alpha receptors.  ER alpha causes cells to proliferate.  Dr. Edward Friedman, a professor at University of Chicago, proposed the Hormone Receptor Model of Breast and Prostate Cancer in his book, “The New Testosterone Treatment- How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer and Alzheimer’s”.  This is the only model that explains all that is known about breast and prostate cancer!

In the article, “Testosterone and breast cancer prevention” (Maturitas 2015), R. Glaser and C. Dimitrakakis published a 7 year interim analysis comparing women, not on hormone replacement therapy to a group of symptomatic perimenopausal/menopausal women using bioidentical testosterone pellets or bioidentical testosterone pellets with anastrozole (anastrozole prevents conversion of testosterone to estradiol, it is commonly taken by patients with breast cancer). The incidence of breast cancer in the testosterone group was 76/100,000 p-y as compared to 390/100,000 p-y in the control group not on hormone replacement therapy.

Breast cancer survivors are generally warned against using hormone replacement therapy after breast cancer treatment, for at least 5 years if not indefinitely.  However, R. Glaser has been following a group of 72 breast cancer patients with varying stages of breast cancer (stages 0-III), who have opted to use testosterone pellets with anastrozole to relieve symptoms of menopause.  It has been over 10 years and there has not been one recurrence of cancer (Yes, I emailed Dr. Glaser right before completing this article.)  Amazing!  Now these patients were estrogen receptor (ER) positive, progesterone receptor (PR) positive (the majority of breast cancers).  There is little data on treatment of ER negative or Human epidermal growth factor (HER) positive patients.  I once asked a senior medical oncologist at Scripps, if she would approve testosterone therapy for a mutual breast cancer patient.  She laughed at my hesitation and reminded me that before my time (and I’m 63) testosterone was used as chemotherapy for breast cancer!

Remarkably, testosterone pellets are also being used as primary treatment of breast cancer by the same research team, in older patients who do not want or who are not candidates for the standard treatment.  Testosterone pellets with anastrozole are being placed directly into the breast, surrounding the cancer and have led to a marked reduction in tumor size.  Of course, the patients also feel great on testosterone. “Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy…” (in Menopause 2013)  “Testosterone and breast cancer prevention” (in Maturitas 2015)

Lastly, testosterone and anastrozole/letrozole pellets are now being investigated to shrink tumor size before surgery and before chemotherapy/surgery.  With the exception of one case report, the publication of data is pending.  The case report discusses a patient with stage 2, grade 3 breast cancer that was over 3 cm in size.  This patient developed cancer while using testosterone pellets with low dose anastrozole.  She made a decision to continue the testosterone pellets (for quality of life) with a higher dose of the aromatase inhibitor Letrozole (prevents testosterone from converting into estradiol).  After 41 days, the tumor had shrunk to 43% of the original size; after 5 weeks of subsequent chemotherapy, the tumor could no longer be found on imaging.  At the time of surgery, there was no remaining invasive breast cancer.  “Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy:  clinical response and therapeutic implications.”  R Glaser et al (in Menopause 2017).

All of these incredible studies have used testosterone in pellet form.  Only testosterone pellets result in constant and predictable levels of testosterone in blood and tissue, and are always bioidentical.