Male Breast cancer is a rare disease with less than 1 of reported cases than of that of female breast cancer although the incidence of the disease has been increasing for the past 30 years. The rarity of the disease makes it an "orphan disease" which are often understudied hence little information is available about its causes, optimal treatments, and medical sequel despite the fact it presents a subtle yet grave threat to men of all ages. Furthermore, research indicate that Male breast cancer patients have a 16% higher risk of developing a second primary cancer than men in the general population, and the risk is more apparent in younger men(Hoang, Argyrios and Hoda). Because the incidence of male breast cancer is rising and presents grave threat, interest in this disease has increased and in this paper, information on the epidemiologic risk factors, genetics, biologic characteristics, and clinical aspects including diagnosis, treatment, and survivorship is covered.
Background
Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading deregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to different sites, causing significant morbidity and, if untreated, death of the host (Ruddon,36). Male breast cancer shares many similarities with breast cancer in women although male patients with breast cancer have lower risk of death from breast cancer compared to female patients. Breast cancer usually affects the milk ducts and lobules but these complex breast features in men are usually underdeveloped because of high testosterone and low estrogen levels at puberty. Because this disease is rare unlike other forms of cancer, and men generally are insensitive to slight changes in their breasts which they consider unnecessary, its detection is usually when it is at an advanced stage.
Epidemiology and Risk Factors
According to Gradishar (662), Male breast cancer is an uncommon disease, with an estimated incidence of one case per 100 000 man-year in the United States of America. Every year, approximately 2140 new cases of breast cancer in men are diagnosed annually, and 450 deaths occur which represents less than 0.5 percent of all cancer deaths in men annually (Siegel et al,228). According to Giordano, Cohen & Buzdar (57) the mean age at diagnosis for men with breast cancer is 67 years, which is 5 years older than the average age at diagnosis for women but a worrying trend is emerging where breast cancer has been reported in male patients ranging in age from 5-92 years. There are no clear identifiable risk factors for male breast cancer though several of them have been proposed, majority of them related to hormonal levels imbalance. These risks are the same as in women. Family history and genetic disposition have been proven to increase the chances of male breast cancer, with high risk linked to a familial history of breast cancer e.g. men with first-degree relations to a breast cancer patient, whether male or female were likely to develop the same, and in patients with Klinefelter's syndrome in which patients carry XXY chromosomes leading to high levels of estrogen-to-androgen ratio in the body (Wisinski &Gradishar, 34). A condition where there is abnormal breast enlargement, gynecomastia has been related though unproven to increasing risks of male breast cancer. Testicular abnormalities such as undescended testes, congenital inguinal hernia, orchiectomy, and orchitis that are likely to lead to high estrogen levels compared to testosterone levels have been postulated to influence breast cancer risk by increasing cell proliferation, thereby increasing the likelihood of DNA damage, as well as promotion of cancer growth (Thomas, Jimenez & McTiernan, 739). Although obesity, low levels of physical activities, liver diseases, tobacco smoking, diet and alcohol consumption have been consistently linked with male breast cancer,tests and trials have not provided strong evidence to conclude these claims. Besides these factors, age seems to play a significant role with high risks increasing as one gets older.
Genetics
Research indicates that in women, between 30% and 86% of inherited breast cancer are estimated to be etiologically linked to germ line mutations in highly penetrant susceptibility genes, such as BRCA1 and BRCA2 (Greene,). BRCA1 and BRCA2 which stand for breast cancer susceptibility gene 1 and breast cancer susceptibility gene 2, respectively are human genes that stabilize the cell's genetic material (DNA) and help prevent uncontrolled cell growth. Mutations in these genes also increase the risk of affected men developing breast cancer, although not at the same degree as women. BRCA1 mutations have been reported in men with breast cancer but often in combination with other risk factors. According to Frank, Deffenbaugh & Reid (1487), 10%-16% of men with breast cancer have been reported to have BRCA1 mutations in series of high-risk families undergoing genetic testing whereas Male breast cancer in patients with BRCA2 mutations tends to present at a younger age bracket. Mutations in other genes like PTEN (Cowden's syndrome), and mismatch repair genes (hMLH1) have been reported in male patients with breast cancer, but investigations are still needed to clearly prove their impact.
Biological Characteristics
At the onset of life, boys and girls usually have similar breast tissue but over time, men lack the same complex breast growth and development as women. This is because high testosterone and low estrogen levels at puberty stop breast development in males. Some milk ducts exist, but they remain undeveloped, and lobules are most often absent (Komen).In rare cases, men can be diagnosed with inflammatory breast cancer, ductal carcinoma in situ (a non-invasive breast cancer) or Paget disease of the breast (Paget disease of the nipple). Paget disease of the breast is a cancer that begins in the milk ducts of the breast tissue, but spreads to the skin of the nipple (Wisinski &Gradishar, 34).It can cause a scaly rash on the skin of the nipple. Although Paget disease of the breast is rare, it occurs more often in men than in women. However, male breast cancer, is usually of the infiltrating ductal type at 81.3% occurrence, where the cancer has spread beyond the cells lining ducts in the breast. This is similar to the breast cancer found in women. Pre-invasive breast cancer is very rare, since men do not have lobules (milk-producing ducts) in their breasts henceresearch has shown that invasive papillary type follows at 12.5%; and invasive lobular type at 6.3 % respectively.Furthermore, in the cases of breast cancer, the rates of estrogen (ER) and progesterone (PR) receptor positivity tests were higher in men compared to women (Journal of Breast Health, 126-129). This might be a pointer to a man's lower estrogen environment which leaves receptor sites more often available for binding with tumor cells (Haylock, 139).
Clinical diagnosis
The most common benign breast condition (not cancer) in men is Gynecomastia which is enlargement of the breast tissue. Although both men and women may develop benign breast conditions, cysts and fibro adenomas conditions are exclusive to women. These conditions can be mistaken for breast cancer but Mammography is used in differentiating gynecomastia from malignant breast disease with their sensitivity and specificity of diagnosis reported to be 92% and 90%, respectively (Evans, Anthony & Turnage, 96-100) Male breast cancer most often occurs in the left breast, commonly appearing as a mass or lump just beneath the nipple (Haylock, 139). Because the male breast is small, this mass is usually in a fixed position, attached to the skin or chest wall. It may also occur in the upper, outer quadrant of the breast or as a mass in the axilla (armpit). Tumor size and lymph node involvement are two clear prognostic factors for male patients with breast cancer whereby tumors measuring 2-5 cm have a 40% higher risk to kill the victims than those with tumors less than 2 cm in maximum diameter (Giordano, Cohen & Buzdar, 55). Similarly, men with lymph node involvement have a 50% higher risk of death than those without lymph node involvement (Giordano, Cohen & Buzdar, 57). The small size of male breast makes mammography tests inconclusive of the extent of nodal development hence Ultrasonography is used to provide information regarding nodal involvement.
Treatment
Local therapy for breast cancer is generally similar in men and women. However, because of the small size of the male breast, Lumpectomy (Breast-conserving surgery) often used on women cannot be done on men. Therefore, the accepted and current trend in male involves a modified radical mastectomy where all of the breast tissue and lymph nodes closest to the breast under the arm are removed (Haylock, 140). This radical approach, however, is changing after retrospective studies indicated that the outcome for men is equally good when treated with less invasive surgery (Turner, Swindell & Bell, 239-243). Presence of a good deal of lymph nodes, either in the axilla or the internal mammary nodes mandates the use of radiation therapy. Adjuvant chemotherapy is used to treat male patients with locally advanced disease that presents a substantial risk of recurrence and death despite the fact that there is little information on its effectiveness in men. Adjuvant chemotherapy is systematic and aims to get rid of cancer cells that may have spread from the breast to other parts of the body. The normal chemotherapy regimen is given over four to eight cycles, one cycles at averagely one-month intervals accompanied by tamoxifen (Nolvadex) for five years to offset the sensitivity of male breast cancer to hormones (Haylock, 139). The side-effects of this treatment are the same to those found in women including deep-vein thrombosis, decreased libido, impotence, mood alterations, hot flashes, and the common hair loss (Anelli, Anelli & Tran, 74-77). Although hormonal therapies like aromatase inhibitors have proven successful in women, same results have not been achieved in men. The treatment of Metastatic breast cancer (also called stage IV or advanced breast cancer) is however complicated and different. Metastatic breast cancer has spread beyond the breast to other organs in the body most often the bones, lungs, liver or brain and hence cannot be cured (Komen). Treatment of metastatic breast cancer focuses on length and quality of life and the type of treatment depends on characteristics of the cancer cells, where the cancer has spread, symptoms and previous breast cancer treatments. Chemotherapy and radiation can shrink or slow the growth of tumors or to ease symptoms of the cancer itself but their side effects affect quality of life hence targeted therapies and hormonal therapies are preferred (Lopez, Natali & Lauro, 502-505).
Survival Rates
The survival rates for male breast cancer are affected by three critical factors namely: age at diagnosis, size of the tumor and more vitally, the presence of lymph nodes. However, because male breast cancer is most often diagnosed at a later stage the long term survival for men with this disease is highly diminished. Furthermore, male breast cancer survivors have an increased risk of developing second primary cancers as findings from the SEER cancer registry database show (Auvinen, 1330-1332). The risk for other cancers, including melanoma and prostate cancer, may also be elevated in male breast cancer survivors, particularly in mutation carriers.
Conclusion
Male breast cancer has been regarded to present less threat to humanity but the recent findings about its steady rise in the past 30 years presents a cause of worry. There needs to be a concerted effort to carry out extensive research and studies on its epidemiology, genetics, biologic characteristics, and clinical aspects to contain its subtle yet dangerous threat.
