ReviewMale breast cancer: a review of the literature
Introduction
Breast cancer is seen infrequently in men. Although breast cancer is the second most commonly diagnosed malignancy in the U.S.A. (excluding non-melanoma skin cancer), fewer than 1% of all cases of breast cancer occur in males. In the U.S.A., male breast cancer constitutes under 1% of all malignancies in men and is responsible for only 0.1% of male cancer deaths1, 2. In 1998, an estimated 1600 new cases of male breast cancer occurred among a total breast cancer incidence of 180 300, with 400 deaths[1].
The earliest reference to breast cancer is in the Edwin Smith Surgical Papyrus from Egypt, which dates from 3000–2500 bc and appears to have referred to a man[3]. The first clinical description of a case is attributed to John of Arderne in the 14th century. After that, breast cancer in males received no further mention until its reappearance in the literature in the late 19th and early 20th century.
Unlike female breast cancer, in which incidence rates are rising throughout the world4, 5, 6, the comparative incidence of male breast cancer has remained relatively stable in most countries7, 8, 9. The prevalence of male breast cancer increases with age[7]. It is rare before the age of 30 years, and the average age at diagnosis is approximately 60 years, which is approximately 10 years older than in females with the disease5, 9, 10, 11, 12, 13, 14.
The incidence of male breast cancer varies by geographical location. It is higher in the U.S.A. and the U.K. than in Finland and Japan[13]. In many countries it parallels the much higher incidence in women, suggesting a similar aetiology, but with clinical progression that is enhanced by the sexual and reproductive function of women. In parts of Africa, the incidence of male breast cancer is relatively high. Egypt, for example, has an incidence rate 12 times that of the U.S.A.[15]. Some sub-Saharan countries have a high male breast cancer incidence that parallels their high female cervical cancer rate, suggesting the hypothesis of a relationship to a sexually transmitted disease in these countries[16]. In a report from Zambia, 15% of breast cancer cases were male[17]. Another plausible consideration for such elevated rates is the increased incidence of liver disease in these countries, with its associated high oestrogen levels.
Knowledge relevant to many aspects of the disease in men is still limited. Treatment strategies in men have been largely guided by the experience in women. We review the available literature.
Section snippets
Aetiology
The aetiology of male breast cancer remains as poorly understood as that of female breast cancer[18], but an imbalance by various mechanisms in the oestrogen–testosterone ratio is probably implicated19, 20. Hormonal alterations due to testicular disease may be an important factor. There is an association with Klinefelter’s syndrome, which may account for approximately 3% of male breast cancers. Also, males who have had mumps orchitis, undescended testes or testicular injury are at increased
Clinical features
Because of the rarity of breast cancer in males, most reported series involve small numbers of patients. The statistical accuracy of clinical characteristics of male breast cancer is, therefore, not fully established. However, the mean age of presentation in most reported series spans 60–65 years, with a range from mid-20s to early 90s. This is approximately 10 years older than the corresponding mean age for breast cancer in women9, 42, 43. The presenting clinical finding in 75–90% of patients
Pathology
Virtually all known histological types of breast cancer have been identified in men. Infiltrating ductal carcinoma is the predominant subtype[60], comprising approximately 70% of cases11, 44. Approximately 15% of patients with localised disease have only ductal carcinoma in situ44, 61. Medullary, tubular, papillary, small cell and mucinous carcinoma constitute less than 15% of cases11, 44. Lobular carcinoma was long thought not to occur in men because of the absence of lobules in the
Prognostic factors
Stage and axillary node status are the most important prognostic indicators in male breast cancer. The TNM system is used for men, as well as women[85]. In non-disseminated cases, the size of the tumour (T status) and the axillary nodal status (N status) are the most important prognostic indicators. Prognosis declines as the tumour size increases, mainly because of the increased risk of axillary or distant metastasis. Five-year survival in one series was 77% for axillary node negative patients
Treatment of local disease
Although radical mastectomy was the treatment of choice in earlier years, less invasive procedures, such as modified radical or simple mastectomy, are now more common. A number of series have not shown improvement in survival for men who underwent more radical procedures96, 97, 98. Axillary nodal dissection is indicated, as clinical assessment of the axilla is unreliable. Postoperative radiation therapy in some series has shown benefit in reducing locoregional recurrence, but no survival
Treatment of metastatic disease
Between 4 and 7% of men with breast cancer present with metastatic disease, and 18–54% of patients treated for localised disease will develop distant metastases. Sites of metastases in men are similar to those in women and include bone, lung, liver, brain and others. Also, up to 39% of treated patients will develop local recurrences. Median survival from the time of presentation with metastatic disease is approximately 26.5 months[14].
For patients with oestrogen receptor positive tumours,
Survival of men versus women
The overall survival for male breast cancer patients, documented in various series, has ranged between 36 and 75% at 5 years12, 117, 118. In general, it has a less favourable outcome than breast cancer in women54, 119. A preponderance of stage III disease (22% in men versus 6% in women) and a higher incidence of lymph node positivity (60% in men versus 38% in women) have been linked to the poorer prognosis44, 119, 120. When age- and stage-matched breast cancer in men and women were compared,
Conclusion
Male breast cancer remains an uncommon disease. Most of our current knowledge regarding its biology, natural history and treatment strategies has been extrapolated from its female counterpart. Much research is needed to characterise further the molecular biological properties of male breast tumours and their prognostic significance, and to devise treatment strategies, including optimal chemotherapy regimens.
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