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04-03-2021 | Breast cancer | News

‘Profound’ estradiol reduction with GnRHa in MALE breast cancer patients

Author: Hannah Kitt

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medwireNews: The addition of a gonadotropin-releasing hormone analog (GnRHa) to tamoxifen or an aromatase inhibitor (AI) decreases estradiol levels of men with hormone receptor (HR)-positive breast cancer, phase 2 trial data show.

“The addition of GnRHa to AI or tamoxifen leads to a more profound suppression of estradiol, which is known to increase survival in premenopausal women,” write Sibylle Loibl (German Breast Group Forschungs GmbH, Neu-Isenburg) and colleagues.

The MALE study, which included 52 men aged a median 61.5 years with HR-positive breast cancer, indicates that “[t]he addition of GnRHa should be […] reconsidered as a treatment option in high-risk patients and should be weighed against increased adverse effects,” says the team.

The men, attending one of 24 German treatment centers, were randomly assigned to receive one of three endocrine therapy regimens: subcutaneous GnRHa every 3 months with either tamoxifen 20 mg/day or the AI exemestane 25 mg/day, or tamoxifen alone.

The majority (94.2%) of patients were treated in the adjuvant setting and had HER2-negative (86.5%), moderately differentiated (57.7%), stage T2 (52.9%), node-negative (52.0%) tumours.

After 3 months, patients taking GnRHa with tamoxifen had an average 84.9% reduction in estradiol levels, from a median of 33.0 ng/L at baseline to 5.0 ng/L, and those given GnRHa with exemestane had a 72.2% reduction, from a median of 27.5 ng/L to 7.5 ng/L.

By contrast, the estradiol levels of patients receiving tamoxifen alone increased by 66.7%, from a median of 27.0 ng/L at baseline to 45.0 ng/L after 3 months.

Pairwise comparisons showed significantly different median changes in estradiol levels in the GnRHa–tamoxifen and GnRHa–exemestane cohorts compared with the tamoxifen alone cohort, with respective decreases of 23.0 ng/L and 18.5 ng/L versus an increase of 17.0 ng/L.

But there was no significant difference in median estradiol level changes between the patients given GnRHa with tamoxifen or exemestane.

After 6 months of treatment, estradiol levels remained suppressed in the patients given GnRHa with tamoxifen or exemestane, while levels were still raised in those given tamoxifen alone. The authors note that the median changes from baseline significantly differed among the treatment arms.

The researchers also looked at how the endocrine treatments affected other hormones and found that, similar to estradiol, follicle-stimulating hormone, luteinizing hormone, and testosterone were significantly decreased after 3 and 6 months of treatment in patients taking GnRHa with tamoxifen or exemestane, but significantly increased in those taking tamoxifen alone.

Writing in JAMA Oncology, the study authors explain that sexual function and quality of life (QoL) were assessed with the International Index of Erectile Function and the Aging Male Symptom score, respectively. And the investigators say they observed “a strong association between the decrease in estradiol and testosterone levels in sexual function and [quality of life].”

Indeed, significantly more patients in the GnRHa groups had erectile dysfunction at 3 and 6 months than those in the tamoxifen alone group, with no clinically meaningful changes seen in the latter group throughout the study.

At 3 months, a significantly greater proportion of patients in the GnRHa versus tamoxifen alone groups also reported reduced QoL. This significant between-group difference in QoL did not persist at 6 months.

Loibl and team note that “[a]ll 3 therapeutic strategies were well tolerated with no new safety signals.”

They conclude: “[T]he 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.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Oncol 2021; doi:10.1001/jamaoncol.2020.7442

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