Male Breast Cancer: A Rare but Serious Disease That Should Not Be Overlooked
Dr. Elvyra Vasilevskaja
Introduction
Breast cancer is the most commonly diagnosed oncological disease in women not only in Lithuania but also in many other countries worldwide. According to data from the Lithuanian Cancer Registry, the disease is diagnosed in almost 1,400 women in Lithuania every year. Male breast cancer is a relatively rare malignant disease. Globally, men account for less than 1% of all breast cancer patients. In Lithuania, 10–16 new cases of male breast cancer are diagnosed annually. It is estimated that in 2018, approximately 2,550 new cases of male breast cancer will be diagnosed in the United States, claiming the lives of 480 men.
The highest incidence of male breast cancer is recorded in Central and Western Africa (approximately 6%). This is associated with the high prevalence of liver diseases in these regions, which leads to hyperestrogenism. As in women, the risk of developing breast cancer in men increases with age. Male breast cancer is diagnosed at an older age, with peak incidence occurring at 65–67 years, on average 5–10 years later than in women (1–3).
In this article, we review the main risk factors and symptoms of breast cancer, as well as aspects of its diagnosis and treatment. We emphasize the importance of educating the public and continuously reminding family physicians and other specialists that not only women but also men are susceptible to this disease.
Risk Factors
Scientific articles describe various risk factors that may be associated with the development of male breast cancer, although in many cases the cause of the disease remains unknown.
Age. Age is one of the main risk factors. The disease is frequently diagnosed in men aged 65 years and older.
Genetic predisposition and family history. As in women, the risk of developing breast cancer in men increases if their first-degree relatives have had breast, ovarian, or colorectal cancer. It has been found that as many as 15–20% of men diagnosed with breast cancer had first-degree relatives with cancer.
Autosomal dominant mutations in the BRCA1 and BRCA2 genes, which can predispose individuals to the development of breast and ovarian cancer, are classified as high-risk cancer genes. Mutations in these genes increase the risk of cancer by more than fourfold compared with the general population. A BRCA2 gene mutation is more strongly associated with the development of breast cancer than a BRCA1 mutation. The likelihood of developing breast cancer in a man with a BRCA1 gene mutation is 1 in 100, while for a BRCA2 gene mutation it is 6 in 100. Although the risk of cancer is considerably lower in the presence of a BRCA1 gene mutation, there is one exception—Ashkenazi Jews. Studies of Ashkenazi men with breast cancer found that 4.5% specifically had a BRCA1 gene mutation.
Other genes known to be associated with the development of breast cancer include TP53 (Li-Fraumeni syndrome), PTEN (a tumor suppressor gene associated with Cowden syndrome), and PALB2 (4).
Conditions altering the balance of estrogens and androgens in the male body. Various conditions can cause an increase in estrogen levels in men, including inherited diseases, exogenous estrogen or testosterone use (estrogen and progesterone preparations are prescribed for testicular and prostate tumors), liver diseases, particularly cirrhosis, thyroid dysfunction, obesity, and marijuana use.
Klinefelter syndrome is a rare genetic disorder in which boys have an additional X chromosome instead of the usual XY sex chromosomes. Patients with this syndrome experience testicular atrophy, gynecomastia (breast enlargement), increased concentrations of gonadotropin hormones (follicle-stimulating and luteinizing hormones), and low blood testosterone levels. In a cohort study conducted a decade ago involving 3,518 men with Klinefelter syndrome, the incidence of and mortality from breast cancer were found to be 19–58 times higher than in the general population. Routine mammographic screening for breast cancer is not recommended for men with Klinefelter syndrome. They should learn how to perform breast self-examination (4).
Testicular diseases. Orchitis, inguinal hernia, cryptorchidism, testicular trauma, and orchiectomy are conditions that lead to decreased androgen secretion and increased estrogen dominance in the male body.
Obesity, due to the development of hyperestrogenism, alcohol consumption, and low levels of physical activity also increase the risk of developing breast cancer (4).
Types, Stages, and Clinical Symptoms of Breast Cancer
The breast is composed largely of fatty tissue containing alveoli and lactiferous ducts (Figure 1). Similar types of breast cancer occur in both men and women. Most malignant tumors begin to develop in the epithelial cells lining the lactiferous ducts (ductal carcinoma) or in the milk-producing lobules (lobular carcinoma). In most cases (85–90%), men are diagnosed with invasive ductal carcinoma (Figure 2). Lobular carcinoma is rare in men. Men have little glandular tissue in the breast, so the tumor usually affects the area around the nipple and areola and is less commonly found in the upper outer quadrant.
Breast cancer in men is often diagnosed at later stages. This is likely because tumors in this location are very rare in men. There is a widespread misconception in society that breast cancer is exclusively a women's disease, while in family medicine practice, tumors in this location are also rarely encountered in men.
Stages of breast cancer:
Stage 0 – the malignant process has not extended beyond the epithelial boundaries of the ducts; carcinoma in situ.
Stage 1 – the diameter of the breast tumor does not exceed 2 cm, with no metastases in the lymph nodes or internal organs.
Stage 2 – this stage of the tumor is characterized by:
• a tumor 2–5 cm in diameter, with no metastases in the axillary lymph nodes;
• a tumor 2–5 cm in diameter, with metastases in the axillary lymph nodes;
• no tumor nodule in the breast, but cancer cells are detected in the axillary lymph nodes;
• a tumor >5 cm in size, with no metastases in the axillary lymph nodes.
Stage 3 – this stage is characterized by:
• a tumor >5 cm in size, with metastases in the axillary lymph nodes;
• a tumor that has spread to the chest wall and may be attached to the chest wall muscles or skin;
• possible metastases in the supraclavicular or infraclavicular lymph nodes.
Stage 4 – advanced breast cancer with metastases to other organs of the body, including the bones, lungs, liver, brain, and others.
Key clinical symptoms that raise suspicion of breast cancer in men include:
• most commonly (in 98% of cases), unilateral breast involvement; according to the literature, left-sided breast tumors are more common;
• 70–90% of patients notice a painless lump near or behind the nipple;
• changes in nipple shape, usually nipple retraction, or nipple discharge;
• bloody discharge from the nipple, although this is rare;
• changes in the color or surface of the breast skin, with the skin over the tumor resembling an orange peel;
• pain or a pulling sensation in the breast and breast enlargement;
• palpable enlargement of the axillary lymph nodes in 40–55% of patients.
Breast pain is a rare symptom of breast cancer and is usually experienced only in advanced stages of the disease. According to a study conducted in Croatia, only 29% of male breast cancers were diagnosed within 3 months of symptom onset. A study conducted in Spain showed that diagnosis takes, on average, more than 10 months. It is therefore crucial that men at increased risk know how to perform breast self-examination and seek medical attention promptly.
Breast Cancer Diagnostic Recommendations
Breast cancer diagnosis is not complicated. A palpable, hard, well-defined mass in the breast usually raises suspicion of a tumor. Early diagnosis is facilitated by the following methods:
Medical history and clinical examination. A comprehensive medical history, including a family history of primary malignancies, medications taken, working conditions, and congenital diseases, together with palpation of the breast and adjacent lymph nodes, can raise suspicion of a possible malignant breast disease.
Mammography. Mammography is one of the non-invasive diagnostic methods important for the early diagnosis of breast cancer. It can detect small changes in the breast. Breast X-ray examination can reveal non-palpable abnormalities. Mammography is also useful in differentiating breast tumors from gynecomastia. The sensitivity and specificity of this examination are approximately 92% and 90%, respectively.
Ultrasound examination. Breast ultrasound is often performed to differentiate changes in breast tissue detected during palpation or mammography and can help distinguish non-malignant lesions, such as cysts. An advantage of this examination compared with mammography is that when breast cancer is suspected, the lesion can be fully evaluated.
Breast biopsy. Biopsy is the most accurate diagnostic method. The final diagnosis is confirmed by microscopic examination of tumor cells obtained from a breast biopsy. The HER2 (human epidermal growth factor receptor 2) test is performed on biopsy material. HER2-positive breast cancer grows much faster, and the course of the disease is more aggressive than that of HER2-negative breast cancer. Determining these receptors is important when selecting the subsequent treatment strategy.
• Fine-needle aspiration biopsy – a thin needle or syringe is used to aspirate cells from the suspected tumor nodule.
• Core needle biopsy – a thick needle is used to obtain a larger amount of tumor tissue. Usually, 3–5 cores of tumor tissue are obtained.
• Excisional biopsy – the tumor nodule is surgically removed and subsequently examined macroscopically and microscopically (7).
To assess the possible spread of the disease and determine whether metastases are present in other organs, chest X-rays, ultrasound examination of internal organs, computed tomography of the necessary body area, or magnetic resonance imaging may be performed.
Differential Diagnosis
Gynecomastia. Breast cancer is most commonly differentiated from gynecomastia. Gynecomastia is characterized by bilateral, symmetrical breast enlargement with poorly defined borders. Gynecomastia is not associated with changes in the breast skin or enlargement of the axillary lymph nodes.
Infectious breast diseases (breast abscess, chest wall skin infections). These conditions are characterized by painful local lesions accompanied by systemic symptoms such as fever and chills.
Granular cell tumors. These are predominantly benign subcutaneous tumors arising from Schwann cells that surround axons in the peripheral nervous system. They are found in the throat, skin, perineum, and breasts. Granular cell tumors are difficult to differentiate from breast cancer on clinical and imaging examinations, and biopsy is often required for differential diagnosis.
Fibromatosis. These are locally aggressive tumors. Biopsy is the basis of differential diagnosis.
Metastatic tumors. Metastases from tumors in other areas of the body to the breast are very rare. Breast metastases may occur in lymphoma, leukemia, melanoma, sarcoma, and prostate, lung, or stomach cancer (4).
Principles of Breast Cancer Treatment
The principles of breast cancer treatment depend on many factors, primarily the stage of breast cancer, degree of differentiation, tumor size, and lymph node involvement. Treatment principles are based on the 2018 recommendations of the American Joint Committee on Cancer.
Stage 0 cancer, or carcinoma in situ – the tumor is usually removed by mastectomy and less commonly by breast-conserving surgery, such as lumpectomy or quadrantectomy, followed by radiation therapy.
Stage I cancer is often well localized, with or without metastases in the regional lymph nodes, and therefore radical mastectomy is usually performed. Before surgery, a sentinel lymph node biopsy is usually performed. If cancer cells are detected in this lymph node, all other axillary lymph nodes on the affected side are removed, provided the patient's condition allows.
Hormone therapy may be used as adjuvant treatment after surgery; tamoxifen is recommended for breast cancer when positive hormone receptors are detected. Chemotherapy may also be used. HER2-positive cancer may be treated with trastuzumab or pertuzumab, which are monoclonal antibodies.
Stage II–III tumors are advanced and may invade muscles or adhere to the chest wall. Therefore, neoadjuvant therapy is administered before surgery with the aim of reducing the tumor and enabling radical surgery. After tumor removal, adjuvant therapy is administered. Hormone receptor-positive tumors are recommended to be treated with tamoxifen for 5 years.
Stage IV metastatic breast cancer is usually incurable, but its course can be effectively controlled. Metastases are most commonly detected in the bones, liver, and lungs. Advanced cancer is treated with chemotherapy, hormone therapy, radiation therapy, and monoclonal antibodies. Radiation therapy and surgical treatment may be used for the local treatment of metastases. The goal of treating metastatic breast cancer is to control the course of the disease for as long as possible, alleviate symptoms that affect the patient, and improve quality of life (2, 7).
Survival Rates
Survival rates for men and women with breast cancer are similar. More than 40% of male breast cancer cases are diagnosed at stage III or IV of the disease. According to 2017 data from the American Cancer Society, the 5-year survival rate for men diagnosed with stage 0 or I breast cancer is 100%. When breast cancer is diagnosed at later stages, survival rates decrease: 92% for stage II, 72% for stage III, and 20% for stage IV.
Survival rates among Black women and men are poorer, with stage III disease and larger tumors diagnosed three times more frequently (2, 5, 10).
Since survival has been shown to correlate directly with the stage of the disease, it is important to suspect a possible malignant disease as early as possible and perform a comprehensive examination of the patient.
Conclusion
Both women and men can develop breast cancer. However, the disease is rarely diagnosed in men. There are certain racial differences in breast cancer incidence, with the disease diagnosed more frequently in Black men than in White men. When stage 0/I breast cancer is diagnosed, the survival rate is 100%.
Early diagnosis is particularly important for patients at increased risk, including those with a family history of breast, ovarian, or colorectal cancer, Klinefelter syndrome, liver diseases, and other risk factors. It is also important for family physicians and physicians in other specialties to remember the main symptoms of the disease and diagnostic recommendations, as overall survival directly correlates with the stage of the disease.
Publication "Internist," No. 7, 2018.
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