Introduction

Breast cancer in men is a rare disease, with a very low proportion, between 0.2 and 1.5% of all malignant tumors in men, and is responsible for 0.1% of deaths¹. In Colombia, the annual incidence is estimated at 0.1 cases per 100,000². The series reviewed show a prevalence of breast cancer in men of 0.2%³.

The risk factors most implicated in male breast cancer are elevated estradiol levels due to testicular abnormalities and genetic alterations such as mutation of the BRCA 1-2 gene or aneuploidies such as Klinefelter syndrome⁴. Other factors described include alcoholism, liver disease, obesity and estrogen exposure. However, the relationship is inconsistent, although it may be cumulative⁵. Among all the proposed factors, the only ones with a proven association are genetic. It is estimated that 15-20% of men with breast cancer have a family history of breast or ovarian cancer, and 10% of all tumors have a genetic predisposition⁶.

The BRCA2 mutation in men is more prevalent (4 to 40%) than the BRCA1 mutation (0 to 4%). Men who inherit the BRCA2 mutation have a cumulative risk of 6.8% of presenting this type of cancer at the age of 70 years, in contrast to those with the BRCA1 mutation, in whom the risk is less than 1.2%. This risk is 80-100 times higher than in the general population⁷.

The clinical diagnosis is made when a mammary nodule is found, being subareolar in 70-90% of cases (Figure 1). The average diameter of the mass can range from 0.5-12 cm (mean: 3-3.5 cm). Other clinical signs include nipple retraction (738%), skin ulceration (14-22%) and telorrhage (415%)⁸ (Figure 2). In many cases there is a delay in diagnosis, due to the lack of knowledge that this disease can affect men; therefore, it is most frequently found in locally advanced stages^9,10.

Author source

Figure 1 Ultrasound of male breast, showing retroareolar circumscribed hypoechoic nodule. 

Author source

Figure 2 Ulceration of the nipple-areola complex. 

The objective of this study was to make a retrospective review of the clinical aspects, diagnosis and treatment of patients who attended the mastology consultation in an oncology unit in the city of Medellin (Colombia).

Methods

This is a retrospective descriptive study of users attended in the mastology consultation at the Medellín clinic (Colombia) by a surgeon, in the period January 1, 2017 and December 31, 2020.

From a total of 1 124 users attended, medical records were searched with ICD code 10 (C509) Malignant tumor of the breast, unspecified part and male sex. Five records were identified, creating an independent database for this cohort of patients. No cases were excluded, as all met the diagnostic criteria, and analysis of the subgroup of 5 cases with a diagnosis of breast carcinoma in men was performed, obtaining demographic data and clinical and pathological characteristics. Data on age, reason for consultation, physical examination, affected side, ultrasound and mammography findings, types of treatment, follow-up and recurrence were included. The exclusive diagnostic criterion was the histopathological study by sharp needle biopsy or study of the surgical specimen.

Descriptive analysis of sociodemographic and clinical variables was performed. Absolute frequencies and percentages, median and ranges were calculated, according to the nature and nonparametric distribution of the variables. The normal distribution was validated using the Shapiro Wilk goodness-of-fit test. SPSS statistics software version 23 was used.

Regarding ethical aspects, the present study is considered a risk-free study, according to the classification established in Article 11 of Resolution No. 008430 of 1993 (issued by the Colombian Ministry of Health) and complies with international standards, the Helsinki declaration, and the ethical guidelines for biomedical research prepared by the Council for International Organizations of Medical Sciences -CIOMS-. This work was approved by the Research Ethics Committee of Clínica Medellín.

Results

Medical records on the experience of a surgeon with male breast cancer at Clínica Medellín from 01/09/2016 to 31/12/2020 were reviewed. A total of 1 124 patients had diagnosis of breast cancer ICD10 code (c509). Filter of ICD10 and male sex was performed, finding 5 patients who met the inclusion criteria, with a prevalence of 0.44%, one of them with bilateral breast cancer.

The median age was 73 years (RIC 17.2). Regarding family history of cancer, one patient had a history in third degree of consanguinity, and in no case was there a report of genetic studies, having been requested in 3 cases. Regarding laterality, 3 cases (60%) were in the right breast, 1 in the left breast (20%), and 1 bilateral (20%). In 60% of the cases (n= 3), the location was retroareolar and in 40% (n= 2) in the upper external quadrant, in all cases as a single lesion (unifocal).

The clinical and histopathological features are presented in Table 1. There were delays in seeking medical attention (patient time), and the time to diagnosis was up to 165 days, while the time to treatment varied ranged from 23 to 60 days.

Table 1 Clinical and histopathological characteristics 

The main symptom manifested by the 5 patients was the presence of mass. The histologic type in all cases was infiltrating ductal; histologic grade 1 occurred in one case (20%), grade 2 in 3 cases (60 %) and grade 3 in one case (20%). Tumor size averaged 2.5 cm (± 3.4 cm). The most common clinical lymph node stage in the axilla was N1-0 followed by N2; most cases (n: 4; 80%) were in a locally advanced clinical stage: 2 cases at stage IIIB, one bilateral case IIIC- IIB and one patient stage IV due to pulmonary involvement.

The most frequent ultrasound finding was a spiculated nodule in 2 cases (40%), a lobulated nodule in 2 cases and a rounded nodule in 1 case (20%). Mammography was performed in only one case (20%); there were no associated microcalcifications.

Histopathological diagnosis was made by ultrasound-guided cutting biopsy (80%), in one case by excisional biopsy (20%). All patients had an infiltrative component. Regarding hormone receptors, all 5 cases (100%) were positive. HER2 evaluation by immunohistochemistry, in 3 cases was negative and in one case indeterminate, where FISH was negative.

Table 2 summarizes the treatment and follow-up. In the neoadjuvant setting, chemotherapy was used in one patient, and another patient in metastatic stage had palliative treatment, in all cases with doxorubicin, cyclophosphamide, paclitaxel (AC-T). Three patients received adjuvant radiotherapy (60%). The percentage of patients who underwent surgery was 80% (n= 4), the surgical technique used in all cases was total mastectomy. Axillary emptying was performed in 3 cases, and sentinel lymph node biopsy was performed in one patient. Positive margins in 2 cases (50%) required margin enlargement, being finally negative.

Table 2 Treatment characteristics and follow-up.  

The median follow-up of the patients was 23 months. At the end of the follow-up period, 3 (60%) patients were alive, 2 (40%) died of cancer. One patient presented locoregional relapse, receiving management with chemotherapy and hormone therapy.

Discussion

Breast cancer is the most common cancer in women in the world, while in men it is considered a rare disease, and few studies address this disease. Traditionally it has been approached analogously to women, however it presents clinical and immuno-phenotypic differences¹¹.

This study found a prevalence of 0.4% of men with breast cancer among the cohort of women with the same diagnosis, and an annual incidence of 1.25 men with the diagnosis per year. Similar findings have been found in the worldliterature, which reports a prevalence between 0.2-1.5%¹, In the Latin American literature there are some case reports, and among the descriptive studies, prevalences have been found to be between 0.2-0.8%^12-14, with an incidence of 1.8 men per year¹⁵. Additionally, a case of bilateral cancer was found.

Some studies have shown that there are significant differences between both sexes. A study of 459,846 women and 2,665 men diagnosed with breast cancer showed that the average age at diagnosis in women was 61.7, while in men it was 69.6¹⁶, similar to what was found in the present study where the median age was 73 years.

The risk factor for male breast cancer with proven association are genetic, the diagnosis merits the request of BRCA 1-2 gene study, and between 15% to 20% of those affected have a family history of breast and ovarian cancer¹⁷; in this study 20% (n = 1) had a family history of breast cancer.

The study found that 80% (n=4) of the cases were diagnosed at a locally advanced and metastatic stage, which is higher than reported in the North American literature¹⁸, but similar to what was found in Latin America, up to 89%¹⁵. A possible hypothesis is that the diagnosis is made late¹⁸. In the present study, delays were found in patient time, the period between the onset of the symptom and the first consultation, and the time to diagnosis when the histologic diagnosis is obtained.

In this study, the histologic type in the series was ductal, all were hormone receptor positive and none had HER2 overexpression. Other studies have also found that luminal intrinsic luminal intrinsic subtypes A and B are more frequent, and in smaller proportion HER2-positive and basal-like tumors, suggesting a better prognosis^19,20. In all cases (100%) they received adjuvant hormonal treatment, similar to that reported by Giordano et al.²¹, who describe that 80% of cases with estrogen receptor expression received adjuvant tamoxifen. The current recommendation for adjuvant hormonal therapy is tamoxifen in all hormone receptor-positive patients¹⁷.

Regarding surgical treatment, in this study all patients with non-metastatic tumors were treated with mastectomy, and in one case sentinel node biopsy was performed. In other Latin American studies, such as that of Ibañez et al.¹⁴ and Angel et al.¹⁵, mastectomy was performed in 100% of patients, with no cases of conservative surgery.

Regarding the management of the axilla, there are only retrospective series on the use of sentinel nodes in men. These have shown adequate diagnostic performance, and additionally the same benefits by avoiding the morbidity of mandatory lymph node dissection²², radiotherapy and chemotherapy, using the same criteria than in women.

With respect to breast cancer prognosis by sex, Anderson et al.¹⁶ found that men had lower 5-year survival than women (0.72 vs. 1.27). However, after adjusting for age, year of diagnosis, stage and treatment, men had longer survival than women (0.78 vs. 0.62).

We consider as limitations that the study is of the respective nature of one surgeon's data-base, with a small number of cases and short follow-up, and therefore does not allow inferences to be made in other scenarios.

In conclusion, breast cancer in men is an infrequent disease, with age of presentation in the seventh decade of life, clinical symptoms of breast mass in all cases and breast ultrasound as the most used diagnostic method and complement in the guide for cutting biopsy. Diagnosis tends to be delayed due to late consultation, and most cases present in advanced stage, with immunophenotyping of A - B luminal predominance. The most commonly used surgical treatment is mastectomy, and adjuvant treatment tends to be homologous to that used in women.