Men with breast cancer ‘deserve attention,’ may benefit from surgery for stage IV disease
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Surgery with systemic therapy improved survival among men with stage IV breast cancer and known ER and PR status, according to study results published in Annals of Surgical Oncology.
The findings should lead to strong consideration of surgery after neoadjuvant chemotherapy for these patients, according to researchers.
“Breast cancer in men deserves attention and the treatment paradigms are changing. We want them to be contemporary with the ones we offer our women patients,” Daleela G. Dodge, MD, FACS, associate professor in the department of surgery in the division of surgical oncology at Penn State Cancer Institute, said during a presentation at last year’s virtual American College of Surgeons Clinical Congress.
The analysis included 539 patients with stage IV breast cancer and known ER and PR status from 2004 to 2017 within the National Cancer Database. Dodge and colleagues examined subgroup differences between treatment modalities received, assessed OS and used HR models to examine factors associated with survival.
Results showed a survival benefit in patients who received trimodal therapy — systemic therapy, surgery and radiation — compared with patients who received systemic therapy alone (HR = 0.62; 95% CI, 0.45-0.84). Patients treated with trimodal therapy and with systemic therapy plus surgery also had superior 5-year OS rates (39% and 24%) when compared with those treated with systemic therapy alone (20%).
Dodge and colleagues found the sequence of treatment significant, with the greatest survival advantage among patients treated with neoadjuvant, preoperative chemotherapy compared with adjuvant, postsurgery chemotherapy in ER-positive patients (HR = 0.342; P < .0244).
Healio spoke with Dodge about the research and the challenges of identifying and treating men with breast cancer, 40% of whom do not get diagnosed until they have stage III or stage IV disease.
Healio: How did this research begin?
Dodge: Our team looked at a database of 12,000 women with de novo stage IV breast cancer and saw that trimodal therapy that included surgery to remove the primary cancer, which is currently not in NCCN guideline treatment recommendations, conferred a survival benefit. Twenty years ago, we may not have been adding much benefit by putting these patients through surgery. But now, with improvements in systemic therapy, our results suggest offering the subgroup of patients who respond to systemic therapy a more aggressive approach that includes surgery. Kelly A. Stahl, MD, a study co-author, then came back to me and asked, “Do you think we should look at it in men?" Remarkably, we found the database had enough male patients with stage IV de novo disease to study and, even more exciting, we reached the same conclusion. In both papers, we also saw that less surgical therapy occurred recently than in the earlier part of the study. People were following NCCN guidelines that say not to treat the primary tumor, but we believe the recommendation against surgery may need to change.
Healio: Does this mean the guidelines should change?
Dodge: The guidelines are always being reevaluated. Our paper will be part of the next review. Another aspect is that if you are walking around with breast cancer — if you can feel it and if it doesn't go away — I think the hopelessness of knowing it’s there can be very difficult. I've found among my patients that having surgery, the removal of the cancer, has provided a psychological benefit.
Healio: What are the challenges in researching breast cancer among men?
Dodge: Their cancer biology — more ER-positive disease, for example — differs somewhat from women’s cancers. However, the treatments are generally very parallel. I think you can extrapolate from one subset to the other subset to a significant degree. Awareness of the signs and symptoms is very important. Certain genetic mutations such as BRCA carry an increased risk for male breast cancer. Being of African descent doubles your risk as a man for developing breast cancer. Having liver disease increases the risk, as does obesity.
Over the last 20 to 25 years, male breast cancer has increased 26%, but as society gets a little fatter and liver disease becomes more common, we may see even higher rates in the future. And just because a cancer is rare doesn't mean it doesn't deserve attention.
Healio: In your study, you found 40% of men with breast cancer present with stage III or stage IV disease. How can that be curtailed?
Dodge: Although women have a lot of breast tissue that can hide the cancer, men generally have cancers that can be found on exam fairly early. In 50% of cases in men the cancer involves the nipple, causing changes, or the mass is located close to the nipple. A hard mass of a cancer is different than a soft, rubbery mass associated with benign gynecomastia, which afflicts many men, and awareness of the difference is very important.
Symmetry is also important. If something is different than on the other side or there is skin retraction, a man should seek evaluation and treatment. Ultrasonography can visualize most of these cancers. If the ultrasound is suspicious, we also obtain a mammography. There are no guidelines that recommend screening men with any imaging modality at this point. And it's more important that male BRCA2 mutation carriers who have a 6% lifetime risk are treated by a physician who is aware of all the additional cancer risks and screens them aggressively, including with comprehensive physical exams.
Healio: How has your own outlook on and knowledge of breast cancer in men changed in the last 15 to 20 years?
Dodge: Male breast was perceived as super rare, but incidence is rising. Since reentering academics, I have seen more men, because clinicians tend to send patients to a tertiary care center for things they don't commonly see. When there are breast changes, we need to work them up and be aggressive so we don't see people presenting with stage IV, or even with stage III disease. Breast cancer is very treatable.
Healio: What’s the next step in your research?
Dodge: I think we're going to stay very active in this arena of de novo stage IV — advocate for more prospective data analysis on those who present with stage IV breast cancer and investigate the utility of surgery for them. When we see these patients who are stage IV, the conversation needs to be, “How can we best treat you? How can we maximize your quality of life?”
Mastectomy and partial mastectomy are both low-morbidity operations. In other cancers we are now offering aggressive treatments, such as in colon cancers that have metastasized to the liver, where aggressive surgical intervention cures up to 30% of the patients. However, these operations have significant rates of complications and some patients never recover fully or return to their premorbid level of activity. With breast cancer, we can offer these operations with a very low risk for significant complications. Our patients generally go home the next morning after mastectomy. Most of my patients go home without narcotics. Surgical resection of the primary, we believe, offers a survival benefit in patients who have breast cancers that are responsive to systemic treatments. This improved survival is primarily because our contemporary systemic therapies have become so much more specific and are so much better at treating the disease, and we believe this now opens the door for reconsideration of adding surgery for those patients who have treatment-responsive cancer.
References:
Stahl KA, et al. Ann Surg Oncol. 2021;doi:10.1245/s10434-020-09244-5.
Stahl KA, et al. Scientific Forum Presentation. Presented at: American College of Surgeons Clinical Congress; Oct. 23-27, 2021; Washington, D.C.
For more information:
Daleela G. Dodge, MD, FACS, can be reached at College of Medicine, Department of Surgery, The Pennsylvania State University, 500 N. University Drive, H151, Hershey, PA 17033; email: ddodge@pennstatehealth.psu.edu.
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