Findings from a first population-based study to assess the 20-year risk of breast cancer specific mortality (BCSM) in nonmetastatic hormone receptor (HR)-positive male breast cancer suggest that patients with male breast cancer face a long-term risk of recurrence and death, which warrants further investigation into better adjuvant treatment options in men with HR-positive disease.<\/p>\n
Notable findings on the late risk of BCSM in men indicate it should not be extrapolated from women when counsel patients according to Dr. Jos\u00e9 P. Leone of the Dana-Farber Cancer Institute in Boston, MA, US and colleagues who published the results on 29 February 2024 in the JAMA Oncology<\/em>.<\/p>\n Historically, patients with male breast cancer have been underrepresented in randomised studies, whether through explicit exclusion or lack of enrolment in trials that technically allowed men. As a result, treatment guidelines and counselling for men with breast cancer have largely been derived from clinical trials in female patients, with supporting data generated by observational and population-based studies in men.<\/p>\n Due to its rarity, invasive breast cancer in men remains understudied. More than 90% of patients with male breast cancer are diagnosed with HR-positive disease, and ERBB2<\/em>-positive disease accounts for 8-12% of male breast cancer cases, and most of these are also HR-positive; HR-negative\/ERBB2<\/em>-positive and triple-negative breast cancer are rare in men. Invasive ductal carcinoma is the most common histologic subtype, and invasive lobular carcinoma makes up a smaller percentage of cases in men than in women. The median age at diagnosis is substantially higher in men than in women, and patients with male breast cancer are more likely to have regional nodal involvement.<\/p>\n The long-term risk of BCSM in women is influenced by disease features at initial diagnosis, including tumour stage, grade, and nodal status. The authors wrote in the background that the impact of these and other factors on the long-term risk of BCSM in patients with male breast cancer is uncertain. Published studies on BCSM beyond 5 years in men with nonmetastatic HR-positive breast cancer have been limited to case series of patients treated at individual institutions. <\/p>\n To report 20-year risks of BCSM and non-BCSM in men with stage I to III HR-positive breast cancer and identify factors associated with late BCSM, they conducted an observational cohort study of men diagnosed with HR-positive breast cancer from 1990 to 2008, by using population-based data from the Surveillance, Epidemiology, and End Results programme.<\/p>\n Men diagnosed with stage I to III HR-positive breast cancer were included in the analysis. Cumulative incidence function was used to estimate the outcomes of baseline clinicopathologic variables regarding cumulative risk of BCSM and non-BCSM since diagnosis. Smoothed hazard estimates over time were plotted for BCSM. Fine and Gray multivariable regression evaluated the association of preselected variables with BCSM, conditional on having survived 5 years. Main <\/strong>o<\/strong>utcome <\/strong>m<\/strong>easure<\/strong> was <\/strong>BCSM.<\/p>\n A total of 2836 men with stage I to III HR-positive breast cancer were included, with a median follow-up of 15.41 (IQR, 12.08-18.67) years. Median age at diagnosis was 67 (IQR, 57-76) years. The cumulative 20-year risk of BCSM was 12.4% for stage I, 26.2% for stage II, and 46.0% for stage III.<\/p>\n Smoothed annual hazard estimates for BCSM revealed an increase in late hazard rates with each incremental node category, reaching a bimodal distribution in N3 and stage III, with each having peaks in hazard rates at 4 and 11 years. Among patients who survived 5 years from diagnosis, the adjusted BCSM risk was higher for those younger than 50 years versus older than 64 years, those with grade II or III\/IV vs grade I tumours, and stage II or III vs stage I disease.<\/p>\n Comparing the present results to earlier studies of women with HR-positive breast cancer reveals differences in the kinetics of the BCSM risk among patients with higher stage disease. The reasons to explain the occurrence of this late peak in HR-positive male breast cancer are unclear. Men have more limited evidence-based endocrine therapy options than women, with tamoxifen being the preferred option for men. Considering the timing of the late peaks and the fact that there is a reduction in the hazard estimates after the peaks are reached raises the issue as to whether endocrine therapy or lack of adherence to it would be a reason for the increase in hazard estimates so many years later.<\/p>\n Other possible explanations may include differences in the tumour biologic factors between female HR-positive breast cancer and its male counterpart. Alternatively, differences in tumour dormancy between sexes or host-related factors, such as differences in tumour microenvironment, may play a role.<\/p>\n Using data from SEER, the ESTIMATE tool was developed to calculate the risk of BCSM, non-BSCM, and all-cause mortality for women with stage I to III HR-positive breast cancer within any time period up to 20 years from diagnosis. At that time, the paucity of data regarding the factors that influence risk of late BCSM in men with early-stage HR-positive breast cancer precluded the development of a similar tool for patients with male breast cancer, which may be possible now according to the authors.<\/p>\n Leone J, Hassett MJ, Freedman RA, et al.<\/em> Mortality Risks Over 20 Years in Men With Stage I to III Hormone Receptor\u2013Positive Breast Cancer<\/a>. J<\/em>AMA Oncol<\/em>ogy<\/em>; Published online 29 February 2024. doi:10.1001\/jamaoncol.2023.7194<\/p>\nReference<\/h3>\n