new testosterone+aromatase inhibitor implant relieves symptoms due 2 estrogendeficncy

[Lani]

This was a poster presentation @ ASCO Breast.

Subcutaneous implants of a combination of testosterone and the aromatase inhibitor anastrozole in postmenopausal breast cancer survivors reportedly improved menopausal symptoms without increasing estradiol levels, setting
the stage for a randomized, controlled phase III trial.

She seemed very much an evangelist for this treatment option!


ASCO Breast: Implants May Quell Hormone Deficiency

A subcutaneous testosterone implant has shown potential to reduce hormone-deficiency symptoms without raising estradiol levels in breast cancer survivors, data from a small clinical series showed.

Combined with the aromatase inhibitor anastrozole (Arimidex), the implant maintained an average testosterone level of 281 ng/dL with associated estradiol levels <30 pg/mL in 43 breast cancer patients.

Implants containing testosterone alone were associated with estradiol levels >30 pg/mL in 50 of 119 postmenopausal women without breast cancer. That compared with five of 75 (6.7%) combination implants in the breast cancer patients, Rebecca L. Glaser, MD, of Wright State University in Dayton, Ohio, reported here at the Breast Cancer Symposium.

"We believe testosterone is beneficial to breast tissue, and, in fact, most of my referrals are from oncologists," Glaser told MedPage Today. "The downside is that testosterone can be aromatized into estradiol, which may stimulate breast tissue.

"So, we came up with the combination of testosterone with an aromatase inhibitor, delivering it subcutaneously. It is extremely well tolerated, there are no compliance issues, and it takes care of the symptoms."

Breast cancer survivors often have severe menopausal-like symptoms owing to treatment-induced hormone deficiency. Clinical and preclinical evidence suggests androgens inhibit mammary epithelial proliferation and breast growth, leading researchers to wonder if adding testosterone to hormone therapy will reduce the breast cancer risk associated with estrogen/progestin treatment.

Glaser and colleagues have evaluated subcutaneous testosterone implants for treatment of hormone deficiency symptoms in pre- and postmenopausal women without breast cancer. In an article currently in press, they have reported that the implants relieve a variety of symptoms, including hot flashes, sleep disturbance, depressed mood, irritability, and fatigue.

Each combination implant contains 60 mg of testosterone and 4 mg of anastrozole, and patients receive two of the implants every 90 days.

Glaser reported findings from a proof-of-concept study to evaluate the combination pellets' effect on estradiol levels in breast cancer survivors. The study involved 43 patients, 38 of whom were more than five years out from diagnosis. The study population consisted of eight patients with initial diagnoses of ductal carcinoma in situ, one with lobular carcinoma in situ, 19 patients with stage I invasive cancer, 10 with stage II, one with stage III, and four with stage IV.

The 43 patients have undergone a total of 75 subcutaneous insertion procedures. In 70 of 75 procedures, serum estradiol levels were ≤30 pg/mL in association with therapeutic levels of testosterone (range 120 to 518 ng/dL). The highest estradiol measured was 53 pg/mL, which occurred on one occasion in a postmenopausal woman with estrogen receptor-negative breast cancer. Subsequent measurements in this same patient were all <30 pg/mL.

No significant adverse effects have occurred in any of the breast cancer survivors who received the testosterone-anastrozole implants, Glaser said. The total number of insertions had increased to 150 by the end of August.

No breast cancer patient has had disease recurrence during treatment with the implants for as long as three years. Additionally, three patients with metastatic breast cancer have had no evidence of disease progression since beginning treatment with the testosterone-anastrozole pellets.

The findings have set the stage for a randomized, placebo-controlled clinical trial of the implants in breast cancer survivors, according to Glaser.

Glaser reported that she had no relevant disclosures.


Primary source: American Society of Clinical Oncology Breast Cancer Symposium
Source reference:
Glaser RL "Subcutaneous testosterone-anastrozole therapy in breast cancer survivors" ASCO Breast 2010; Abstract 221.

[Debbie L.]

This is very interesting. Good catch, Lani.

It has always seemed to me that with Tamoxifen, local estrogen supplementation (vaginal creams, suppositories, or ring) might be okay because the Tamoxifen would block any systemic uptake, particularly in the breast.

For an AI, it would seem that would not work in the breast (to supplement with estrogen, feeling safe because of the AI), because the AI doesn't affect already-present estradiol.

But I hadn't thought it thru, for things upstream of an estradiol (like testosterone), combined with an AI. I'm still not clear on why testosterone, un-converted, would help with menopausal symptoms, but if it does, that seems really important!

Thinking, thinking, and tending toward getting excited, too. What do you think, Lani, AA, and others? Am I missing something?

Debbie Laxague

[AlaskaAngel]

I'm puzzling it out too.

(I'm a hybrid of sorts, having used tamoxifen for 1 3/4 years but with no AI use -- and then having done the testosterone trial, with continuing to use the compounded testosterone cream per the 2004 Mayo clinic trial intermittently, including at present.)

My desire for the use of the testosterone was partly to help add back in some of the bodily muscle percentage that was lost during chemotherapy, which then helps to put more muscle "pull" back against the bones for weightbearing, and that helps to keep the bones healthier. My interpretation of the 2004 trial was that it was really too brief to gather good info (each person actually received the testosterone for just 4 weeks, with blinded crossover to or from none). At the time the concern was that the testosterone might contribute to the estradiol level. The 2004 trial was intended primarily to measure any return of sensuality/sexuality as well as mood, but not muscle/bone balance. And there was no identification of use of AI or not in that trial.

I know Vic has also been interested in the past.

I wonder if there is some element of positive result happening here in regard to reduction of AI pain that is related to restoration of better (healthier) muscle/bone balance.

A.A.

P.S. I wonder what the ages of those in the study were, in terms of how postmenopausal/menopausal/premenopausal status changes the effect, with the AI. I gather that a majority were more than 5 years out from treatment, but that still could put the majority under age 55, and yet the majority of breast cancer patients are over 55.

[AlaskaAngel]

In looking at the abstract, that does emphasize the bone/muscle benefit obtained with use of testosterone, as well as enhancing immune function.

From the abstract, "Testosterone-anastrozole therapy was effective in treating symptoms of androgen (hormone) deficiency."

I wonder how that was measured and which symptoms it helped with.

A.A.

[AlaskaAngel]

Unfortunately, there is a pervasive and prevalent lack of communication with patients about this topic prior to making tough decisions or borderline decisions about treatment. At the very least, those who are contemplating treatment should consider specifically going over this issue thoroughly and openly with their medical providers to make sure everybody is on the same page about it and not in denial about it.

Here is another trial for women who have completed initial treatment that is trying to help women who are suffering from this problem and who are interested in helping to find out what might help.

Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients (E-String)

This study is currently recruiting participants.
Verified by University of California, San Francisco, June 2008

ClinicalTrials.gov Identifier: NCT00698035

[Rich66]

May be just an issue for advanced cancers after becoming resistant to estrogen blocking...
but I think there is some research looking at upregulated androgen receptor activity in resistant BC.

The good news is that a promising phase III prostate cancer driug Abiraterone Acetate, may be helpful to breast cancer:

LINK

Scientists have long known that prostate cancer growth, survival and invasion are fueled by the male hormone testosterone. In cases of advanced, metastatic prostate cancer, physicians routinely prescribe ADT to stop production of testosterone and cut off the “fuel” for this cancer that affects more than 16 million men worldwide. However, during the course of treatment, many men become resistant to current androgen deprivation treatments and their disease recurs. Abiraterone has been shown to be effective in treating hormone-resistant or hormone-refractory cases. It blocks the formation of testosterone by inhibiting CYP17A1, an enzyme involved in the formation of testosterone that can occur at the site of metastatic tumor lesions.
“The data on Abiraterone is exciting and we hope to see final FDA approval soon,” said Jonathan W. Simons, MD, president and CEO of PCF. “Clinicians will have a powerful new tool to stem the progression of prostate cancer and extend patients’ lives. We are also encouraged that Phase I/II clinical trials evaluating Abiraterone acetate in advanced breast cancer patients are also underway, emphasizing how discoveries in one area of cancer research can provide benefits in others.”

With Mom and Dad both suffering hormonal cancers, I'm definitely watching this one.