Tamoxifen or Aromatase Inhibitors Plus GnRHa Sustained Decreases in Estradiol Levels for Male Patients With Breast Cancer

Treatment with aromatase inhibitors (AIs) or tamoxifen plus gonadotropin-releasing hormone analogue (GnRHa) led to a sustained decrease in estradiol levels for male patients with breast cancer compared with treatment with tamoxifen alone, according to data published in JAMA Oncology.

The examination occurred at a 3-month follow-up, which also showed that the decrease in hormonal parameters due to the addition of GnRHa to treatment was associated with decreased sexual function and quality-of-life (QOL) for patients.

“The addition of GnRHa to AIs or tamoxifen leads to a more profound suppression of estradiol, which is known to increase survival in premenopausal women,” wrote the investigators. “It seems that [men with breast cancer] can be treated according to premenopausal [breast cancer] due to the comparable observations of increased estradiol suppression.”

The median estradiol levels after 3 months increased by 67% (a change of +17.0 ng/L) for patients on tamoxifen, while the levels decreased by 85% (−23.0 ng/L) and 72% (−18.5 ng/L) with tamoxifen and Ais plus GnRHa, respectively (P < .001).

More, a 6-month follow-up found that the estradiol levels sustained their 3-month trends, increasing by 41% (a change of +12 ng/L) with tamoxifen, while decreasing by 61% (−19.5 ng/L) and 64% (−17.0 ng/L) with the tamoxifen and AI combinations, respectively (P < .001).

When evaluating sexual function and QOL for this cohort of patients, the data indicated a decrease in both parameters when GnRHa was added to treatment whereas treatment with tamoxifen alone left sexual function and QOL for patients unchanged.

The multicenter, phase 2 randomized MALE clinical trial (NCT01638247) recruited 56 men with hormone receptor (HR)–positive breast cancer, 52 of whom started treatment. Median age of the patients was 61.5 years (range, 37-83 years). Three of the patients discontinued treatment prematurely and 50 patients were ultimately evaluable for the study’s primary end point.

“The MALE study is the first randomized phase 2 trial investigating the effects of different endocrine therapies on levels of estrogen and other hormonal parameters and their influence on sexual function and QOL in male patients with HR-positive [breast cancer],” wrote the investigators.

The primary end point of the data was estradiol levels measured from baseline to 3-months, while secondary end points included estradiol level changes after 6 months, as well as changes in additional hormonal parameters, adverse effects, sexual function, and QOL after both 3 and 6 months.

The data come with its share of limitations, including its focus on estradiol levels between each arm only, limiting its ability to provide insights on cancer outcomes for patients. More, the small sample size and lack of data for an AI-alone arm limited the quality of data for the research team.

“The addition of GnRHa should be therefore reconsidered as a treatment option in high-risk patients and should be weighed against increased adverse effects,” wrote the investigators. “Nevertheless, the influence on survival and adverse effects should be further investigated in a phase 3 trial. Due to the low incidence of male (breast cancer), international collaborations are required to do so.”

Reference:

Reinisch M, Seiler S, Hauzenberger T, et al. Efficacy of endocrine therapy for the treatment of breast cancer in men: results from the MALE phase 2 randomized clinical trial. JAMA Oncol. February 4, 2021. doi:10.1001/jamaoncol.2020.7442