BEYOND TREATMENT: CAN LIFESTYLE CHANGE CANCER BIOLOGY?

Dr. Neil Iyengar Brings the Science of Precision Lifestyle Medicine to the October 2026 Male Breast Cancer Medical Summit

What if exercise could be prescribed with the same attention to dose that oncologists bring to medication? What if diet could influence biological pathways involved in tumor growth? And what if the next evolution in cancer care involved not choosing between medical treatment and lifestyle intervention—but scientifically determining how the two can work together?

These are among the provocative questions Dr. Neil Iyengar will bring to the October 2026 Male Breast Cancer Medical Summit.

Iyengar, a medical oncologist and physician-scientist who serves as Section Chief of Breast Medical Oncology and Director of Cancer Survivorship Services at Winship Cancer Institute of Emory University, is studying lifestyle intervention from a distinctly oncologic perspective. His interest extends beyond helping patients simply “feel better.” His research asks whether structured diet, exercise, weight management, and body-composition interventions can actually modify cancer biology and potentially improve response to conventional therapy.

That distinction makes his upcoming Summit presentation especially compelling.

From Wellness to Cancer Biology

Exercise, nutritional support, counseling, yoga, mental-health services, and social interventions have long demonstrated value in improving quality of life during and after cancer treatment. Iyengar describes the next scientific question as considerably more ambitious: Can researchers leverage those benefits to actually change cancer biology?

Much of this investigation has emerged from research into obesity and cancer. Obesity is associated with multiple cancers and, following a breast cancer diagnosis, with poorer outcomes, including increased risk of recurrence or faster progression. Most historical breast cancer data have come from women, but Iyengar points to a growing—although still limited—body of evidence suggesting that obesity may also be an important risk factor in male breast cancer.

The biological explanation is increasingly sophisticated. Dysfunctional adipose tissue can promote inflammation, alter cytokine signaling, contribute to DNA damage and oxidative stress, affect insulin pathways, alter immune function and the gut microbiome, and provide energy that developing cancer cells may exploit. This understanding is allowing investigators to approach lifestyle intervention almost as they would drug development: identify biological pathways, design an intervention capable of modifying them, and then measure the response.

Exercise as a Precision Intervention

Perhaps the most striking part of Iyengar’s work concerns exercise.

Evidence suggests exercise may increase tumor blood flow, improve drug delivery, alter molecular signaling involved in tumor-cell growth, and potentially reduce metastatic behavior. Observational studies involving more than 17,000 patients have also associated exercise with approximately a 40 percent reduction in breast cancer-specific mortality. Iyengar carefully emphasizes that such findings do not mean exercise replaces cancer treatment. Rather, they raise the possibility that exercise may complement standard therapy in biologically meaningful ways.

The question then becomes surprisingly similar to pharmacology: What is the correct dose?

Iyengar and colleagues recently completed a multicenter Phase I structured exercise trial involving patients with hormone receptor-positive metastatic breast cancer receiving first-line therapy. Fifty-four participants were assigned exercise doses ranging from 90 to 375 minutes per week. Treadmills were delivered to participants’ homes, sessions were remotely supervised by exercise physiologists, and wearable technology monitored fitness, body composition, blood pressure, sleep, and other measures.

Nearly all tested exercise doses proved feasible except the highest—375 minutes weekly. Most intriguing, the best one-year progression-free survival rate in this early trial was observed in the 225-minute-per-week group. Iyengar stresses that this finding must now be confirmed in larger Phase II and Phase III studies. It nevertheless provides an important foundation for studying exercise not simply as general advice, but as an individualized intervention with a potentially definable therapeutic dose.

Diet, Body Composition and a Remarkable Result

Iyengar’s research also challenges the idea that the number on a scale tells the entire story.

In a recently completed Phase II trial supported by the American Cancer Society, patients with Stage I–III estrogen-receptor-positive breast cancer receiving anti-estrogen therapy were randomized to a six-month structured plant-based diet plus exercise intervention or health education. Participants underwent biological sampling, while the intervention was highly individualized: treadmills were delivered to homes, exercise was prescribed according to individual needs, and meals were designed around personalized caloric, protein and carbohydrate requirements.

The results Iyengar presented are striking.

Participants in the intensive lifestyle arm lost approximately 17 percent of total body weight, compared with approximately 5 percent in the control group. More importantly, the intervention group demonstrated a 7 percent gain in lean mass despite the substantial weight loss. For Iyengar, this highlights why lifestyle intervention remains important even as powerful medical weight-loss therapies such as GLP-1 receptor agonists become increasingly available: weight loss alone and healthier body composition are not necessarily the same outcome.

The Emerging Model: Precision Lifestyle Oncology

Iyengar ultimately envisions cancer care in which oncologists prescribe not only anticancer therapy but also individualized lifestyle plans informed by a patient’s biology, environment, genetics, cancer type, treatment and body composition.

And this may be the most important measure of his research program’s success.

The work has moved the conversation beyond generic instructions to “eat better and exercise.” His team has completed controlled clinical studies, demonstrated that sophisticated lifestyle interventions can be delivered even into patients’ homes, identified feasible exercise doses, produced substantial improvements in weight and lean body mass, and generated hypotheses now ready for larger clinical testing.

The final question—whether these interventions can reliably improve cancer-specific survival across different populations—still requires larger and longer trials. But the research trajectory is clear.

Lifestyle oncology is moving from recommendation toward measurement, from general wellness toward precision intervention, and from the margins of cancer care toward rigorous clinical investigation.

At the October Summit, Dr. Neil Iyengar will show us just how far that science has already come—and where it may take cancer treatment next.

 

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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20 Questions to Ask After a Breast Biopsy

Source: NCC Patient Education

A biopsy is performed to determine whether suspicious breast tissue is benign, atypical, precancerous, or cancerous. These questions can help patients—women and men—understand the immediate recovery period, pathology findings, and possible next steps.

Why an Educated Patient Is Better Prepared

The period following a breast biopsy can be filled with uncertainty. Patients may be managing physical discomfort while also waiting for results that could affect their health, family, work, and future. During this emotionally demanding time, it can be difficult to know what to ask, which information matters, or what should happen next.

Becoming an educated patient does not mean attempting to become one’s own physician. It means participating actively in the healthcare conversation. Patients who understand the basic language of biopsy findings are better prepared to ask focused questions, recognize when an explanation is incomplete, request clarification, and make informed decisions with their clinical team. They are also more likely to understand the difference between a benign result, a high-risk or atypical finding, a noninvasive cancer, and an invasive diagnosis.

Education can also reduce avoidable confusion. A pathology report may contain information about tumor type, grade, hormone-receptor status, HER2 status, and other characteristics that could influence treatment. Knowing that these details exist helps patients ask whether all necessary testing has been completed, whether the pathology agrees with the imaging, and whether another specialist or second opinion may be appropriate.

Most importantly, informed participation gives patients a greater sense of direction during a time when they may feel powerless. Asking questions is not challenging the physician’s expertise; it is helping the medical team understand what the patient needs to know. No patient should leave an appointment uncertain about the diagnosis, warning signs, next steps, or whom to contact with additional concerns.

The goal is not to have every answer before entering the examination room. The goal is to arrive prepared to ask the questions that will lead to clearer answers, shared decisions, and more confident care.

Immediately After the Biopsy

1. What discomfort, bruising, swelling, or bleeding is considered normal after this biopsy?
2. What warning signs—such as increasing redness, warmth, drainage, fever, severe pain, or persistent bleeding—should prompt me to call you immediately?
3. How should I care for the biopsy site, and when may I remove the dressing or shower?
4. Are there any temporary restrictions on exercise, lifting, work, medications, or blood thinners?
5. Was a biopsy marker clip placed, and will it remain safely in my breast?

Understanding the Results

6. When should I expect the pathology results, and who will contact me to explain them?
7. Will I receive a complete copy of the pathology report and related imaging reports?
8. Did the biopsy sample adequately represent the suspicious area, or could additional tissue be needed?
9. Do the pathology findings agree with what was seen on the mammogram, ultrasound, MRI, or physical examination?
10. Is the finding benign, high-risk or atypical, noninvasive, or invasive—and what does that classification mean?
11. If the result is benign, does it fully explain the abnormality that led to the biopsy?
12. If atypical cells or a high-risk lesion were found, what is the likelihood that nearby tissue could contain a more significant abnormality?

If Cancer Is Identified

13. What exact type of breast cancer was found, and is it noninvasive or invasive?
14. What is the tumor grade, and what does the grade suggest about how the cancer may behave?
15. Have estrogen receptor, progesterone receptor, and HER2 tests been completed, and how could these biomarkers influence treatment?
16. Are any pathology findings still pending or uncertain, and should the tissue be reviewed by a breast-pathology specialist?
17. Do I need additional breast imaging, lymph-node evaluation, laboratory testing, or other studies before treatment decisions are made?
18. Should I receive genetic counseling or inherited genetic testing based on my diagnosis, age, sex, ancestry, or family history?

Planning What Comes Next

19. Which specialists should be involved in my care, and how soon should I meet with a breast surgeon, medical oncologist, radiation oncologist, plastic surgeon, or genetic counselor?
20. What decisions must be made now, what decisions can safely wait, and is there enough time to obtain a second opinion?

Patients should also ask for a written next-step plan, the name and telephone number of their clinical contact, and instructions explaining whom to call after regular office hours. A biopsy is the beginning of the diagnostic conversation—not the end of it.

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These questions reflect the role of biopsy in confirming a diagnosis and guiding further testing or treatment. Breast-biopsy complications are uncommon, but persistent bleeding and signs of infection require medical attention. 

This educational feature is brought to you in part by the Male Breast Cancer Global Alliance and the National Cancer Collective (NCC), organizations committed to expanding awareness, strengthening patient and family education, and connecting individuals affected by cancer with trusted information, meaningful advocacy, and supportive resources. Together, they are working to ensure that no patient or caregiver faces cancer without knowledge, guidance, or community.  Educational information from the National Cancer Collective; it does not replace individualized medical advice.

 

Thermography, Thermology and Male Breast Cancer

Promise, Limits and the Work of Dr. Phil Hoekstra

 By: Lennard M. Goetze, Ed.D

Thermal imaging has attracted renewed interest as medicine searches for comfortable, radiation-free methods of assessing breast health. The terms thermography and thermology are often used interchangeably, but they describe different parts of the process. Understanding that distinction is essential—especially when discussing male breast cancer and the work of Dr. Phil Hoekstra.

 Thermography is the imaging technology. A sensitive infrared camera measures heat emitted from the skin and converts those measurements into a color-coded image called a thermogram. The procedure is non-contact, does not compress the breast and does not expose the patient to ionizing radiation.

MEDICAL THERMOLOGY is the broader clinical discipline. It includes standardized patient preparation, controlled room conditions, image acquisition, recognition of thermal patterns, comparison between corresponding areas of the body, clinical interpretation and reporting. Thermography produces the image; thermology provides the scientific framework through which that image is evaluated.

 Why Breast Health Became Thermography’s Best-Known Application: Breast thermography became prominent because the breast is relatively superficial and accessible to infrared measurement. Increased blood flow, inflammation, vascular changes and altered metabolic activity can produce differences in skin temperature. A thermogram may therefore identify asymmetry or an unusual heat pattern that deserves clinical attention.

 Thermography was historically investigated and promoted as a breast-cancer screening method. However, research produced widely variable results, partly because early equipment, acquisition conditions and interpretive criteria were inconsistent. A systematic review found substantial variation in sensitivity and specificity and concluded that evidence was insufficient to support breast thermography as either a screening or diagnostic test by itself.

 Today, the FDA states that thermography has not been demonstrated to be an effective stand-alone test for breast-cancer screening or early detection. It is cleared only as an adjunctive tool, meaning that it may provide supplementary physiologic information but must not replace mammography or another clinically indicated examination. A suspicious thermal pattern is not proof of cancer, while a normal thermogram cannot rule cancer out. FDA, systematic review

 

Dr. Phil Hoekstra’s Contribution

Dr. Phil Hoekstra has devoted decades to thermal imaging and is widely identified within the thermology community as an experienced interpreter and educator. According to Therma-Scan’s published history, Hoekstra and his father established the organization in 1972. His work has emphasized moving beyond the casual production of colorful heat pictures toward a disciplined process involving standardized imaging, clinical-quality interpretation and comparison of thermal findings over time.

 It would be inaccurate, however, to say that Hoekstra “converted thermography into a diagnostic test for cancer.” No thermologist can diagnose breast cancer from temperature patterns alone. The more defensible description is that Hoekstra helped advance thermography toward medical thermology: a structured adjunctive assessment intended to identify physiologic findings that may justify further evaluation. Cancer diagnosis still requires conventional clinical investigation and, ultimately, tissue pathology when warranted. Calling anyone the world’s “leading diagnostic expert” would require independent comparative evidence. Hoekstra can responsibly be described as a longstanding authority and highly experienced specialist in medical thermology, but the limits of the technology must remain clear.

 

What Thermology May Offer Men: Male breast cancer is frequently diagnosed after a man notices a lump, nipple retraction, discharge, skin alteration or another physical change. Because routine population screening is generally not recommended for average-risk men, awareness and prompt evaluation of symptoms are especially important.

Thermology offers practical advantages: it is non-invasive, radiation-free, compression-free and capable of documenting surface-temperature patterns. It may be useful as an adjunct for recording physiologic asymmetry and directing attention to a region requiring conventional examination. These qualities also may make some men more willing to participate in an initial breast-health assessment.

Nevertheless, the claim that mammography “fails men” is not supported by current evidence. Mammography can be highly accurate in symptomatic men; one study reported 92% sensitivity, 90% specificity and a 99% negative predictive value. Ultrasound is also valuable for characterizing a palpable abnormality. The American College of Radiology recommends diagnostic mammography or digital breast tomosynthesis for many men aged 25 or older with an indeterminate breast mass, followed by ultrasound when findings are suspicious or inconclusive. Male mammography study, ACR criteria

 Thermology’s most responsible future is therefore not as a replacement for mammography, ultrasound, MRI or biopsy, but as one component of an integrated diagnostic pathway. For men, the best “new solution” is not reliance on one technology. It is greater awareness, rapid clinical evaluation and thoughtful use of complementary physiologic and structural information—followed by biopsy whenever cancer must be confirmed.

 

Lymphedema Can Appear Years After Treatment

The Delayed Risk of Lymphedema

Written by: Lennard M. Goetze, Ed.D  / Edited by: Daniel Root

For many male breast cancer survivors, treatment ends with the expectation that postoperative problems will gradually fade. Lymphedema does not always follow that timetable. It may develop soon after surgery or radiation, but it can also appear months or years later. Survivors therefore need lifelong awareness—not lifelong fear—of changes in the arm, hand, chest wall, breast or underarm.

Lymphedema occurs when the lymphatic system cannot adequately transport fluid from tissues. Breast cancer surgery may remove or disrupt axillary lymph nodes and vessels, while radiation can produce inflammation and scarring that further restrict lymphatic drainage. The resulting accumulation of protein-rich fluid may cause swelling, inflammation and, over time, thickening or hardening of the tissues. The National Cancer Institute recognizes cancer treatment as an important cause of secondary lymphedema. National Cancer Institute

Risk varies considerably. Axillary lymph-node dissection generally creates greater risk than sentinel lymph-node biopsy because more lymphatic structures are removed. Regional lymph-node radiation, extensive surgery, postoperative infection, higher body weight and reduced mobility may increase risk further. Research involving breast cancer populations—most of whom have been women—suggests that approximately one in five patients undergoing axillary lymph-node dissection may eventually develop lymphedema. Male-specific rates remain less clearly established because men are underrepresented in breast cancer survivorship research.

The earliest symptoms can be subtle. A man may notice that his watch feels tighter, his sleeve fits differently or one hand appears slightly fuller. The arm may feel heavy, fatigued, tight or unusually warm before obvious swelling is visible. Other signs include reduced flexibility, difficulty bending the elbow, aching, tingling, visible skin impressions or swelling around the chest, underarm or surgical scar.

A composite experience frequently described by survivors sounds like this: “My arm did not suddenly balloon. It simply felt heavier at the end of the day, and my shirt cuff became tighter.” Another common observation is, “I thought the chest swelling was ordinary weight gain until I realized it was only on the treated side.” These are representative statements, not quotations from identified patients, but they illustrate why early symptoms can be overlooked.

New swelling should not automatically be labeled lymphedema. Infection, a blood clot, medication effects, heart or kidney disease, and cancer recurrence can also produce swelling. Rapid onset, redness, increasing warmth, fever, severe pain, chest pain or shortness of breath requires prompt medical assessment. A specialist may diagnose lymphedema through history, examination and limb measurements. Bioimpedance spectroscopy, tissue assessment or imaging may be used when the diagnosis is uncertain or when subclinical changes are being monitored.

Although lymphedema is usually considered a chronic condition, early management can reduce swelling, preserve function and help prevent progression. Treatment should be individualized by a clinician trained in lymphedema care. Complete decongestive therapy commonly combines compression, exercise, skin care, education and, when appropriate, manual lymphatic drainage. Compression may involve a fitted sleeve and glove, chest garment or multilayer bandaging. An improperly fitted garment can constrict tissue or worsen symptoms, so professional measurement is important.

Exercise is not generally prohibited. Current clinical guidance supports gradual, progressive, supervised exercise, including resistance training, for people at risk of or living with breast-cancer–related lymphedema. Muscle activity helps move lymphatic fluid, while exercise supports weight management, strength and shoulder mobility. Sudden, excessive loading without conditioning is less advisable than measured progression accompanied by symptom monitoring. Academy of Oncologic Physical Therapy

Skin protection is also important because lymphedematous tissue is more vulnerable to infection. Survivors should moisturize dry skin, clean cuts promptly, protect against burns and insect bites, and seek medical care for spreading redness, warmth, tenderness or fever. These may indicate cellulitis, which can further damage lymphatic vessels and requires timely antibiotic treatment.

No precaution can guarantee prevention, and developing lymphedema does not mean that a survivor failed to care for himself. Some traditional restrictions involving blood-pressure measurements, injections, blood draws or air travel are supported by limited or inconsistent evidence and should be personalized rather than presented as absolute rules.

The most useful strategy is recognition followed by action. Establishing baseline arm measurements after treatment, reporting persistent changes and obtaining early assessment from a certified lymphedema therapist can make the condition more manageable. A survivor’s treatment may be over, but attention to lymphatic health remains an important part of long-term recovery.

References

1. Davies C, Levenhagen K, Ryans K, Perdomo M, Gilchrist L. Interventions for breast cancer–related lymphedema: clinical practice guideline from the Academy of Oncologic Physical Therapy of APTA. Phys Ther. 2020;100(7):1163-1179. doi:10.1093/ptj/pzaa087
2. Executive Committee of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2020 consensus document of the International Society of Lymphology. Lymphology. 2020;53(1):3-19. PubMed
3. Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg. 2018;7(4):379-403. doi:10.21037/gs.2017.11.04
4. Kwan JYY, Famiyeh P, Su J, et al. Development and validation of a risk model for breast cancer-related lymphedema. JAMA Netw Open. 2020;3(11):e2024373. doi:10.1001/jamanetworkopen.2020.24373
5. Ren Y, Kebede MA, Ogunleye AA, et al. Burden of lymphedema in long-term breast cancer survivors by race and age. Cancer. 2022;128(23):4119-4128. doi:10.1002/cncr.34489
6. Jørgensen MG, Toyserkani NM, Hansen FG, Bygum A, Sørensen JA. The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment. NPJ Breast Cancer. 2021;7:70. doi:10.1038/s41523-021-00276-y
7. McNeely ML, Harris SR, Dolgoy ND, et al. Update to the Canadian clinical practice guideline for best-practice management of breast cancer-related lymphedema: study protocol. CMAJ Open. 2022;10(2):E338-E347. doi:10.9778/cmajo.20200276
8. National Cancer Institute. Lymphedema and cancer treatment. Updated March 6, 2024. Accessed August 30, 2026. https://www.cancer.gov/about-cancer/treatment/side-effects/lymphedema

Closing the Male Breast Cancer Research Gap

 The Missing Men in Breast Cancer Research

Written by: Lennard Goetze, Ed.D / Edited by: Daniel Root

Male breast cancer is uncommon, accounting for approximately 1% of breast cancer diagnoses. Its rarity, however, has produced a serious clinical problem: men have historically been excluded from many of the studies used to establish breast cancer treatment standards. As a result, physicians frequently treat men using evidence generated primarily—or sometimes entirely—in women. Many of these treatment principles are biologically reasonable and clinically effective, but important male-specific questions remain incompletely answered.

A 2018 analysis of 426 breast cancer clinical trials conducted between 2000 and 2017 found that 65% explicitly excluded men. Across the trials included in the enrollment analysis, only 0.42% of participants were male. The investigators also found that some exclusions occurred without a clear scientific justification. These findings should not be interpreted to mean that every current recommendation is unreliable. They demonstrate that the strength and directness of the evidence vary considerably. JAMA Oncology

The American Society of Clinical Oncology’s guideline for male breast cancer illustrates this limitation. Its evidence review identified only 26 descriptive reports or observational studies; prospective randomized evidence involving men was extremely limited. Consequently, many recommendations were adapted from research in women and supplemented by expert consensus. Surgery, radiation, chemotherapy, HER2-directed treatment and management of metastatic disease generally follow the same principles used for women because tumors are classified by stage and molecular characteristics—not simply by the patient’s sex. Nevertheless, direct male data are needed to determine whether effectiveness, dosing, toxicity and long-term outcomes are truly equivalent. ASCO guideline

Endocrine therapy is one of the clearest examples. Most male breast cancers are estrogen-receptor positive, making hormone-blocking treatment essential for many patients. ASCO recommends tamoxifen for men with hormone-receptor-positive early breast cancer when endocrine therapy is indicated, generally for an initial five years. Men who remain at high risk and tolerate treatment may be offered an additional five years. If tamoxifen cannot be used, an aromatase inhibitor may be combined with gonadotropin-releasing hormone suppression. An aromatase inhibitor used alone may not suppress estrogen adequately in men because the testes continue to contribute to hormonal production.

These recommendations are clinically rational, but the unanswered questions are substantial. Researchers need better information about optimal treatment duration, comparative effectiveness and male-specific adverse effects. Tamoxifen can cause hot flashes, sexual dysfunction, reduced libido, mood changes, weight changes and an increased risk of blood clots. These effects may lead some men to interrupt or discontinue therapy. Yet male-specific adherence strategies and symptom-management interventions have received far less study than treatment efficacy in women.

The research gap extends into survivorship. Men can experience lymphedema, neuropathy, persistent pain, fatigue, bone loss, infertility, body-image distress, anxiety, depression and fear of recurrence. Mastectomy can alter a man’s relationship with his chest and sense of masculinity, while being treated in environments designed almost exclusively for women may intensify isolation. Without sufficient male participation, researchers cannot accurately measure how frequently these problems occur, which patients are most vulnerable or which interventions offer the greatest benefit.

Representation also matters in genetic medicine. All men diagnosed with breast cancer should be offered genetic counseling and germline genetic testing, according to ASCO. Pathogenic variants—particularly in BRCA2, but also BRCA1 and several other cancer-susceptibility genes—can influence treatment, future cancer surveillance and risk assessment for relatives. Male participation in genomic studies can help clarify whether certain inherited variants, tumor mutations or molecular pathways affect disease behavior and treatment response differently.

There has been meaningful progress. In 2020, the U.S. Food and Drug Administration finalized guidance recommending that men be included in breast cancer drug-development trials unless a scientific reason justifies exclusion. The FDA also recognizes that conventional male-only randomized trials may be difficult because the disease is rare. It therefore supports combining clinical-trial evidence with observational studies, registries, electronic health records and other real-world data when appropriate. FDA guidance

Inclusion alone is not enough. Trial results should report male enrollment, treatment exposure, adverse effects and outcomes separately whenever the numbers permit meaningful analysis. Research networks must also collaborate internationally because no single cancer center is likely to enroll enough men rapidly. Remote participation, decentralized follow-up and partnerships with male breast cancer advocacy organizations may reduce geographical and social barriers.

Men should ask their oncology teams whether an appropriate clinical trial, registry, tissue study or survivorship study is available. Participation is always voluntary, and declining a study should never compromise standard care. Greater participation, however, can help move male breast cancer treatment from reasonable extrapolation toward directly demonstrated evidence. Men are not merely a small subgroup within breast cancer research. They are a clinically distinct population whose treatment experiences, toxicities and survivorship needs deserve to be measured, understood and represented.

References

1. Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849-1863. doi:10.1200/JCO.19.03120
2. Duma N, Hoversten KP, Ruddy KJ. Exclusion of male patients in breast cancer clinical trials. JNCI Cancer Spectr. 2018;2(2):pky018. doi:10.1093/jncics/pky018
3. Corrigan KL, Mainwaring W, Miller AB, et al. Exclusion of men from randomized phase III breast cancer clinical trials. Oncologist. 2020;25(6):e990-e992. doi:10.1634/theoncologist.2019-0871
4. 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. 2021;7(4):565-572. doi:10.1001/jamaoncol.2020.7442
5. Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018;29(2):405-417. doi:10.1093/annonc/mdx651
6. Ruddy KJ, Giobbie-Hurder A, Giordano SH, et al. Quality of life and symptoms in male breast cancer survivors. Breast. 2013;22(2):197-199. doi:10.1016/j.breast.2012.12.014
7. US Food and Drug Administration. Male Breast Cancer: Developing Drugs for Treatment—Guidance for Industry. Published August 2020. Accessed August 30, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/male-breast-cancer-developing-drugs-treatment