MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.
Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.
“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.
Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.
“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”
One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.
“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.
The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.
On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.
“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”
GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.
To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.
As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.
“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.
Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”
Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”
Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”
Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.
“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”
Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.