MBC is considered to be a rare disease, and bilateral, simultaneous MBC is extremely rare [1–4]. MBC is said to be more common in elderly patients compared with the disease in females . It has been reported that the characteristics of MBC are similar to those of postmenopausal female breast cancer , but there are also reports that hormonal receptor studies and studies of the therapeutic efficacy of aromatase inhibitors indicate MBC to differ from female breast cancer [12–15]. Various risk factors have been pointed out for MBC, including BRCA2 gene anomalies , Klinefelter's syndrome , a genetic background such as a familial history of breast cancer, hormonal abnormalities due to obesity or testicular disease (cryptorchidism, mumps, orchitis, orchiectomy), exposure to radiation [1–4]. With regard to hormonal abnormalities, it has been reported that MBC is caused by an imbalance between estrogen and testosterone [4, 9]. Breast cancer has been observed to occur in patients who were administered an estrogen for a long period of time , and estrogen is thought to play an important role in the development of MBC since the plasma concentration of this hormone is higher in MBC patients than in normal males [1–3, 9]. It is said that the production, metabolism and bioavailability of estrogen are enhanced in the subcutaneous tissues of obese males as a result of activation of aromatase, a decrease in sex-hormone-binding globulin (SHBG) and for these reasons obesity has been reported as a risk factor for MBC . On the other hand, with regard to testosterone, castration for the purpose of gender transformation or prostate gland therapy is said to increase the risk of MBC, while testicular dysfunction due to mumps or cryptorchidism alters the levels of estrogens, androgens and gonadotropins and is also thought to increase the risk of MBC . Prolactin is involved in the differentiation and development of normal breast tissue, and there have been reports of bilateral breast cancer in patients with pituitary tumor, especially when accompanied by hyperprolactinemia [6, 7]. Also, because administration of prolactin has been shown to cause breast cancer in animal studies, this hormone is thought to be strongly involved in the development of this malignancy . However, prolactin is produced in an autocrine and/or paracrine manner by breast cancer cells and normal breast cells, and it is said that its activity is expressed only at the cellular level. Thus, it has been judged that it does not exert any influence on prolactin production by the pituitary, and that pituitary prolactin production is not involved in the development of breast cancer .
BRCA2 testing was not performed on our present patient. However, since there was no familial history of breast cancer, it can be surmised that the cause of the disease was the hormonal disturbances rather than genetic factors. Moreover, the facts that this patient was rather young (47 years old) to have this disease and that the disease was simultaneously bilateral point to the existence of high risk factors.
A chromosomal study showed the patient to have a normal male karyotype of 46XY, but he had complications of hypospadias and male potential hypogonadism. Hypospadias is one of the most commonly occurring congenital abnormalities, and one of its causes is thought to be hormonal abnormalities during the fetal stage . In addition, although androgen gene and/or androgen receptor gene anomalies might be thought to be involved , this patient showed only a mild degree of abnormality of the external sex organs and presented a normal male appearance in terms of the body type, development of body hair. Also, the fact that there was only a slight increase in the testosterone level following a loading test provides further evidence negating involvement of these two genetic anomalies in this patient. However, there is a possibility that the hypospadias was familial in nature, and thus we cannot rule out the possible existence of other genetic anomalies in the patient.
In an attempt to elucidate the causative mechanism of the bilateral breast cancer in this Japanese male, we performed various hormone tests. Imaging studies found almost no normal testicular tissue, but in the hCG loading test testosterone increased even if only slightly, and although the hormone secretion function of the testes was disturbed, the function can nevertheless be considered to have been about half of normal. This suggests that a partial Leydig cell function of cyst wall do exist. It can be surmised that this was because stimulation by LH and FSH due to feedback arising from the testicular potential hypogonadism caused secretion of testosterone from testes and from adrenal glands and thus maintained a normal serum testosterone level.
In addition, since the patient showed a tendency to obesity, the finding that the E1 level was slightly increased even though the testosterone level was normal can be thought to have been a result of estrogen production via aromatase in the adipose cells. We did not measure the level of SHBG, but it can be assumed that SHBG was nearly normal since the level of free testosterone was normal. An SHBG abnormality would affect the estrogen activity, but there was no striking evidence of such an effect in this patient. There is doubt regarding whether a slight elevation of only E1 in men has any clinical significance. Pathologically, the disease developed bilaterally in this patient, and histopathological studies of multiple sections of the resected specimen found almost no normal ductal tissue and almost entirely breast cancer cells. We cannot exclude the possibility that the breast cancer in this patient developed only due to these hormonal abnormalities. Measurements were carried out three times at set intervals, but each time the PRL level was slightly elevated. As noted earlier, PRL has been ruled out as a cause of breast cancer . However, there have been reports of bilateral MBC accompanied by hyperprolactinemia [6, 7], and in this light we cannot exclude the possibility that PRL may indeed be somehow involved. In addition, there have been reports that MBC clearly differs from postmenopausal female breast cancer, including recommendation of use of a gonadotropin-releasing hormone analog to interrupt the feedback from the pituitary that occurs at the time of administration of an aromatase inhibitor as therapy for breast cancer in males [12, 13]. In the future, we hope to further elucidate the causes of MBC.