Endocrine Therapies May Lower Estradiol Levels in Men With Breast Cancer

Treating men with breast cancer with either an aromatase inhibitor or Soltamox (tamoxifen) plus gonadotropin-releasing hormone analogue lowered estradiol levels compared with Soltamox alone, according to results from the phase 2 MALE trial published in JAMA Oncology.

“It seems that male (breast cancer) can be treated according to premenopausal (breast cancer) due to the comparable observations of increased estradiol suppression,” the study authors wrote. “The addition of (gonadotropin-releasing hormone analogue) should be therefore reconsidered as a treatment option in high-risk patients and should be weighed against increased adverse effects.”

Men with breast cancer account for an estimated 1% of all breast cancer cases. In addition, more than 90% of men with breast cancer are hormone receptor (HR) positive. Research is limited on how different endocrine approaches to treatment can affect men, in particular quality of life, side effects and sexual function.

In this current study, researchers analyzed data from 50 men with HR-positive breast cancer. Patients were assigned treatment with 20 mg per day of Soltamox alone (17 patients), 20 mg per day of Soltamox plus gonadotropin-releasing hormone analogue (15 patients) or 25 mg per day of the aromatase inhibitor Aromasin (exemestane) plus gonadotropin-releasing hormone analogue (18 patients). All treatments were administered for six months in the adjuvant (treatment after primary treatment), neoadjuvant (therapy to shrink a tumor before the main treatment) or metastatic setting (when the disease spread to another region of the body).

Researchers monitored for changes in estradiol levels (a form of estrogen) from the beginning of the study to three months, in addition to estradiol level changes at six months, side effects, changes in other hormonal parameters, quality of life at three months and six months, and sexual function.

At three months, median estradiol levels increased by 67% in patients assigned Soltamox alone, decreased by 85% in those assigned Soltamox plus gonadotropin-releasing hormone analogue and decreased by 72% in patients assigned Aromasin plus gonadotropin-releasing hormone analogue. Estradiol levels at six months increased by 41% in the Soltamox alone group, decreased by 61% in the Soltamox plus gonadotropin-releasing hormone analogue group and decreased by 64% in the Aromasin plus gonadotropin-releasing hormone analogue group.

Quality of life and sexual function decreased when gonadotropin-releasing hormone analogue was added to treatment, although these factors were unchanged with Soltamox alone.

“The study was only powered to adequately detect changes in estradiol values between the arms, not to give any information on cancer outcome,” the study authors wrote. “The presented differences in adverse effects, sexual function and (quality of life) are descriptive and support the findings of the laboratory values. A potential limitation of the study is the small sample size and no arm with an (aromatase inhibitor) alone, which was thought to be potentially detrimental for the given reasons.”

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