Men with breast cancer are more likely to die than their female counterparts, across all stages of disease, with the disparity persisting even when clinical characteristics, such as cancer types, treatment and access to care are considered, according to a study by Vanderbilt University researchers. The persistent disparity, derived from an analysis of data from the National Cancer Database, suggests a possible distinct cancer biology, less effective treatment or compliance issues, and perhaps unhealthy lifestyles among men may be responsible for the lower overall survival rates, said Dr Xiao-Ou Shu, the study's senior author.
The five-year mortality rate for men was 19% higher than for women. Additional studies are needed to identify the causes, she said, but any such studies would likely require international consortia because male breast cancer is so rare, accounting for less than 1% of cases.
"It is so rare, it would be extremely difficult for any single institute to recruit a sufficient number of patients for research," said Shu, associate director for global health and co-leader of the Cancer Epidemiology Research Programme at Vanderbilt-Ingram Cancer Centre.
The study used 11 years of registry data from 1 January, 2004, to 31 December, 2014, which included 1.8m female patients but only 16,025 male patients. About 85% of male breast cancer is ER-positive, a proportion that is higher than female breast cancer patients (75%).
"That is a cancer type where patients usually fare better because we have a hormonal treatment," Shu said. "We have a lot of treatment options for that type of breast cancer. In theory, men should have better outcomes and have lower mortality as women do if the treatment is equally effective.
"The question is whether there are some other biological differences between ER-positive male breast and ER-positive female breast cancer. We don't know," Shu said.
Previous studies have shown that men may not be as compliant with hormonal treatments as women, Shu said. Other factors that may influence mortality rates among men could be lifestyle factors, such as smoking, alcohol consumption, physical inactivity and obesity.
Clinical characteristics and undertreatments were associated with 63% of the sex-related mortality disparity. "The bottom line is that we need more studies specifically focused on male breast cancer," Shu said.
Importance: Survival differences between male and female patients with breast cancer have been reported, but the underlying factors associated with the disparity have not been fully studied. This understanding is fundamental to developing strategies for cancer treatment and survivorship care.
Objective: To compare mortality between male and female patients with breast cancer and quantitatively evaluate the factors associated with sex-based disparity in mortality.
Design, Setting, and Participants: This large, nationwide, registry-based cohort study used the National Cancer Database to identify and obtain data on patients who received a breast cancer diagnosis between January 1, 2004, and December 31, 2014. After exclusions, the final study population comprised 1 816 733 patients. Statistical analyses were conducted from September 1, 2018, to January 15, 2019.
Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were 3-year and 5-year mortality. Mortality differences were evaluated by Kaplan-Meier analysis. The roles of race/ethnicity, clinical characteristics, treatments, and access-to-care factors in the association between sex and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age.
Results: In total, 16 025 male (mean [SD] age, 63.3 [13.0] years) and 1 800 708 female (mean [SD] age, 59.9 [13.3] years) patients with breast cancer were included in the study. Compared with female patients, male patients had higher mortality across all stages. For men, the overall survival rate was 45.8% (95% CI, 49.5-54.0; P < .001), the 3-year rate was 86.4% (95% CI, 85.9-87.0; P < .001), and the 5-year rate was 77.6% (95% CI, 76.8-78.3; P < .001). For women, the overall survival rate was 60.4% (95% CI, 58.7-62.0; P < .001), the 3-year rate was 91.7% (95% CI, 91.7-91.8; P < .001), and the 5-year rate was 86.4% (95% CI, 86.4-86.5; P < .001). Overall, clinical characteristics and undertreatments were associated with a 63.3% excess mortality rate for male patients. A higher proportion of excess deaths in men were explained by these factors in the first 3 years after breast cancer diagnosis (66.0%) and in all patients with early-stage cancer (30.5% for stage I and 13.6% for stage II). However, sex remained a significant factor associated with overall mortality (adjusted hazard ratio [HR], 1.19; 95% CI, 1.16-1.23) as well as mortality at 3-year (adjusted HR, 1.15; 95% CI, 1.10-1.21) and 5-year (adjusted HR, 1.19; 95% CI, 1.14-1.23) analyses, even after adjustment for clinical characteristics, treatment factors, age, race/ethnicity, and access to care.
Conclusions and Relevance: This study found that mortality after cancer diagnosis was higher among male patients with breast cancer compared with their female counterparts. Such disparity appeared to persist after accounting for clinical characteristics, treatment factors, and access to care, suggesting that other factors (particularly additional biological attributes, treatment compliance, and lifestyle factors) should be identified to help in eliminating this disparity.
Fei Wang, Xiang Shu, Ingrid Meszoely, Tuya Pal, Ingrid A Mayer, Zhigang Yu, Wei Zheng, Christina E Bailey, Xiao-Ou Shu