2026 MEDICAL SUMMIT SPEAKER REVIEW: Closing the Evidence Gap in Male Breast Cancer

Dr. Jose Pablo Leone Brings the ETHAN Trial to the 2026 Male Breast Cancer Medical Summit

When Dr. Jose Pablo Leone takes the stage as part of the Male Breast Cancer Global Alliance’s October Medical Summit, he will be discussing more than a clinical trial. He will be addressing one of the persistent problems confronting men diagnosed with breast cancer: How much of what we prescribe to men has actually been studied specifically in men?

For decades, male breast cancer treatment has necessarily drawn heavily upon research conducted predominantly among women. Yet biology, hormonal environments, treatment tolerability, and therapeutic response cannot simply be assumed to be identical. Dr. Leone, a medical oncologist at Dana-Farber Cancer Institute who treats men with breast cancer, is helping move the field toward something patients and advocates have long sought: evidence generated specifically from men.

At the center of his Summit presentation will be ETHAN (TBCRC-059), a Phase II clinical trial comparing endocrine therapies for men with early-stage breast cancer. The study is attempting to answer several fundamental treatment questions that remain surprisingly unresolved.

Tamoxifen remains the standard adjuvant endocrine therapy for most men with hormone receptor-positive breast cancer. But important uncertainties remain regarding other endocrine approaches. How effective are aromatase inhibitors in men with early-stage disease? Does combining an aromatase inhibitor with gonadal suppression produce greater activity than tamoxifen? Can the addition of a CDK4/6 inhibitor increase treatment effectiveness? And if a CDK4/6 inhibitor is used, what endocrine therapy should accompany it?

These are not abstract scientific questions. The answers could influence how physicians treat men with breast cancer for years to come.

A Trial Built Specifically Around Men

ETHAN plans to enroll 60 men with Stage I, II, or III estrogen- and/or progesterone-receptor-positive, HER2-negative breast cancer—a profile Dr. Leone notes represents approximately 95 percent of male breast cancer cases. Participants are randomized among treatment strategies involving tamoxifen, anastrozole, gonadal suppression with degarelix, and, during the later treatment phase, the CDK4/6 inhibitor abemaciclib.

Importantly, the trial examines what happens biologically while the tumor is still present. After an initial three-week treatment period, participants undergo a research biopsy. Treatment continues before surgery, allowing investigators to examine how individual tumors respond to the different endocrine strategies.

Two major measurements anchor the study: reduction in Ki67, a marker associated with tumor-cell proliferation, and the Residual Cancer Burden Index, which evaluates the amount of cancer remaining at surgery following treatment.

But ETHAN extends well beyond those two measurements.

Researchers are examining estradiol and testosterone levels, treatment safety, side effects, feasibility, quality of life, and patient-reported outcomes. Tumor samples are being collected at multiple points so investigators can compare molecular changes before and after treatment. Blood analyses are also being incorporated, and the research team is working to evaluate circulating tumor DNA—an increasingly important tool for understanding and tracking cancer, but one for which considerably less is known specifically in men.

The study's molecular ambitions are particularly significant. Investigators plan to explore genomic characteristics associated with response, hereditary mutations such as BRCA alterations, tumor-cell death, gene signatures associated with treatment sensitivity, tumor heterogeneity, and circulating tumor DNA. The larger question behind these analyses is increasingly central to precision oncology: Which treatment works best, for which patient, and why?

Progress—and the Challenge Ahead

As of September 1, 2026, Dr. Leone reported that 27 men had enrolled, with another participant in screening. The trial was operating at nine sites across the United States, with additional expansion underway. That geographic growth matters. Male breast cancer is uncommon, and recruiting sufficient numbers of eligible men into a prospective clinical trial is inherently difficult. Expanding the number of participating centers brings the research closer to patients and reduces the travel burden that can otherwise make participation impractical.

Dr. Leone is equally clear that the work is not finished. The study needs 60 participants, and enrollment has progressed more slowly than originally anticipated. Because participants must enter the study before breast surgery, awareness at the moment of diagnosis is critical. Men cannot participate after the tumor has already been surgically removed.

This makes advocacy an active component of research progress. Physicians, cancer organizations, survivors, families, and advocates can help simply by making newly diagnosed men aware that trials such as ETHAN exist.

Research Success Is Also Measured by Momentum

ETHAN has not yet produced the final comparative efficacy results it was designed to generate, so its success should not be described as a therapeutic conclusion. But there is already meaningful success in what the research infrastructure has accomplished.

Dr. Leone reported that the study enrolled 10 additional patients compared with his presentation the previous year, evidence that recruitment is moving forward despite the inherent difficulty of conducting a trial in a rare patient population. The study has expanded nationally, established collaborations among major cancer centers, incorporated sophisticated molecular investigations, and created a research platform dedicated specifically to answering questions about men with breast cancer.

That may ultimately be one of the most important messages Dr. Leone brings to the October Summit: progress in male breast cancer will not come from assuming that evidence from another population is sufficient. It will come from studying men, enrolling men, measuring their responses, and building the evidence that has been missing for too long.

ETHAN represents that movement in action. Its final answers are still ahead—but the research is advancing, participation is growing, and the scientific community is getting closer to evidence that could help define a more precise and better-informed standard of care for men with breast cancer.

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This article and accompanying video clip contain advance excerpts from a presentation scheduled for the 2026 Male Breast Cancer Global Alliance Medical Summit, taking place October 23–24, 2026. This feature is intended solely as an overview of the speaker’s forthcoming Summit presentation and does not constitute the complete presentation. © 2026 Male Breast Cancer Global Alliance. No portion of this article, video clip, presentation overview, or related materials may be copied, reproduced, distributed, republished, or otherwise used without the express written permission of the MBCGA and its Board of Directors.