Long-term survival of male patients with invasive breast cancer in Southern Taiwan

2.1 Study patients

In this retrospective study, a total of 28 male patients were included from a population of initially 4300 patients with invasive breast cancer treated at the Cancer Center of Kaohsiung Chang Gung Memorial Hospital between January 2006 and June 2017. The diagnosis of breast cancer was established through radiological diagnosis, assessment by surgical oncologists, and pathological histologic assessment, following standardized pathologic criteria. The patients were assessed based on the 2010 pathologic tumor (T), lymph node (N) and metastasis (M) staging criteria of the American Joint Committee on Cancer. Patient survival was determined by analyzing factors such as primary tumor size, characteristics of surrounding structures, number and location of regional lymph nodes, presence/absence of an extracapsular extension, and presence/absence of distant metastasis [19]. The detailed information is shown in a previous publication [20]. Approximately 99% of the patients (4272 patients) were excluded due to being female breast cancer or having carcinoma in situ.

2.2 Data collection

The hospital records of patients were examined by well-trained senior chart reviewers using a standardized data collection form. Information, including demographic details, pre-existing comorbidities and medications administered at admission and discharge, was extracted from nursing and medical histories. Guidelines for identifying primary MBC were followed [19]. Following the International Classification of Cancer, T was used to represent the primary tumor size and extent, N was used to indicate nearby lymph node involvement, and M denoted the presence of metastasis [19]. Information on the year of breast cancer diagnosis was collected. Surgical treatment for breast cancer comprised any surgical resection of the primary tumor, with details on tumor size, degree of violation, lymph node metastasis at diagnosis, and distant metastatic dissemination. The tumor histology was classified into five subtypes: intraductal carcinoma, mucinous carcinoma, papillary carcinoma, other specified carcinoma and carcinoma. Additional data included tumor location (left-sided or right-sided tumors), tumor size, primary site, cause of death and survival time (calculated as the difference between the date of diagnosis and the study’s cut-off date (03 July 2017)).

2.3 Statistical analyses

Statistical analyses were conducted using the SPSS software (v23.0, SPSS Inc., Chicago, IL, USA). Prognostic predictors and all-cause mortality associated with discrete variables were identified using the chi-squared test, and continuous variables were assessed using the two-sample t-test. Cumulative survival rates among breast cancer patients across different factor strata were estimated using the Kaplan-Meier method for categorical variables. The results are presented as mean values along with their corresponding standard deviations.

4.1 Clinical implications

This retrospective study provides an analysis of 28 MBC patients treated at a single medical center. Although such as cancer stage (p = 0.034), pathological N stage (p = 0.0001) and the presence of distant metastasis (p = 0.007) were identified to be significant factors affecting the survival of MBC in univariate Cox regression analysis, subsequent multivariate Cox regression analysis showed that these were not independent variables.

In this study, the term “elderly” generally refers to individuals aged over 65 [1]. The median age at the diagnosis of MBC was 63.7 years. Among all MBC cases, 60.7% occurred in males aged 65 years or older, while 39.3% were below 65 years old. The Kaplan-Meier analysis revealed differences in the characteristics of MBC in Korea among patients who developed the condition at ages 60–69 (24.9%) and 70–79 years (23.5%) (log-rank test, p = 0.388). Univariate analyses demonstrated a significant association between mortality and older age (p < 0.001), indicating that older people have a greater risk of succumbing to the diseases. These findings diverge from the results of a previous study [1]. Compared to female breast cancer patients, MBC was previously considered an aggressive type of cancer with poor prognoses. However, in regards to the average age at diagnosis for MBC, the cut-off age is 67 years, which is 5 to 10 years later than that for women [21, 22]. Similar to most carcinomas, the risk of developing MBC increases with age [23]. A study population from the Portuguese Institute of Oncology of Porto included 111 cases of MBC treated at the same Cancer Center from 1980 to 2012 and surveilled them for a maximum of 23 years and reported that most cases presented with ductal carcinomas (90.1%), followed by papillary histopathology, with a rare occurrence of lobular carcinoma (9.9%). In this present study, ductal carcinoma accounted for 60.7% of the histopathological types, while others accounted for 36.3%. Both the estimated 5- and 10-year survival rates for male patients were 57.1%. MBCs were predominantly located in the left breast (78.6%) compared to the right breast (21.4%), and individuals with left breast cancer had the highest mortality rates (18.0%) (univariate Cox regression, p = 0.312). These findings align with those of a previously published study, which reported no significant difference in laterality between men and women (p = 0.085) [24]. Data from the American College of Surgeons study, comprising 109,795 breast cancer cases, found that left and right breast cancers accounted for 52.4% and 46.9%, respectively, and the highest mortality rates were observed in 2822 (52.4%) individuals with left breast cancer [25]. A retrospective study at a single institute involving a cohort of 155 breast cancer patients treated between 2009 and 2013 reported that left-sided tumors were identified in 50.3% of patients, whereas right-sided tumors were observed in 49.7% of patients. Furthermore, the study revealed that left-sided breast cancer had poorer outcomes compared to right-sided tumors (hazard ratio: 1.05; 95% CI: 1.01–1.08) [26].

In this study, of the 78.6% of MBC cases located in the left breast (22 cases), 5 died due to breast cancer and 2 due to other diseases. When examining patients who underwent radiotherapy, other studies did not find any significant impact on mortality from cardiovascular disease, irrespective of the cancer side and its association with radiotherapy (p = 0.672). However, our study at the Korea Medical Center revealed a notable increase in cardiovascular events among patients who received radiation on the left side, especially when combined with anthracycline therapy. Specifically, this risk was higher for those who exceeded a cumulative doxorubicin-equivalent dose of 250 mg/m² over an average follow-up period of 47.1 months. Previous research has indicated that the risk of cardiovascular disease significantly rises at least 10 years after exposure to radiation [27]. A meta-analysis from 1966 to 2015, focusing on breast cancer patients, found that individuals who underwent radiotherapy had a greater risk of coronary heart disease and cardiac mortality compared to those who did not receive radiotherapy. Furthermore, patients who underwent left-sided radiotherapy had a higher risk of developing coronary heart disease and experiencing cardiac-related deaths compared to those who underwent right-sided radiotherapy [28]. However, the lack of a clear link between radiotherapy and cardiovascular disease mortality in MBC patients may be because individuals with left-sided breast cancer are less likely to be selected for radiotherapy due to the proximity of the tumor to the heart [29]. Evaluating breast stiffness pathology relies on breast compression during mammography, necessitating more frequent screenings to improve the early detection of breast cancer [30]. Consequently, further research on radiation dosage to the heart and its connection to cardiovascular disease mortality is essential to better understand a safe radiation threshold that enhances cancer treatment response while simultaneously minimizing the risk of cardiovascular disease in breast cancer patients. The occurrence of MBC observed in our study mirrored the global occurrence pattern, with most of our patients presenting with early breast cancer and estrogen receptor-positive disease. The predominant treatment approach involved modified radical mastectomy followed by adjuvant systemic therapy [31]. Regarding treatment, recent studies have indicated the efficacy of melatonin in breast cancer; however, the optimal dosage and timing have not been fully elucidated, necessitating further investigation. Nonetheless, melatonin remains a promising candidate in this regard [32].

4.2 Strengths and limitations

This study focuses on the long-term survival of MBC patients from Southern Taiwan. Among the 28 MBC patients, three were diagnosed in other hospitals and were excluded owing to incomplete information (1 received chemotherapy at our hospital, 2 did not receive treatment). A higher proportion of male patients presented with more advanced disease compared to their female counterparts. It should be noted that there is still a significant concern among the general public regarding MBC. Owing to a lack of awareness, men tend to disregard symptoms such as breast swelling. Additionally, a breast cancer diagnosis can induce psychological anxiety, fear of future disease prognosis and life-related issues, leading to negative emotions. Therefore, the best prognosis is attainable when breast cancer is diagnosed at an early stage. Interventions that focus on raising awareness and providing psychological support through breast cancer education among men could greatly contribute to improving treatment outcomes and patient prognosis.