Journal of Surgical Oncology 44:180-184 (1990)

Cancer of the Male Breast

TADAOKI MORIMOTO, MD, KANSEI KOMAKI, MD, TAKASHI YAMAKAWA, MD,

TAKASHI TANAKA, MD, YUKEN OOMINE, MD, YASUNOKI KONISHI, MD,

TOSHlAKl MORI, MD, AND YASUMASA MONDEN, MD

From the Second Department of Surgery, School of Medicine, The Unwersity of Tokushima, lapan

The purpose of this study was to investigate the biological behavior of male breast cancer. We evaluated 11 cases of male breast cancer with respect to tumor growth, extent of disease, hormone receptor status, and histological grade of the malignancy, in comparison with 241 cases of female breast cancer. The duration of symptoms was 8.6 k 9.1 months in males and 8.5 k 18.6 months in females. The incidences of stages I, 11, and 111 were 46%, 27%, and 27%, respectively, in male breast cancer, and 3896, 49%, and 13% in female breast cancer. Metastasis to the lymph node was negative in 60% of the male patients and 54% of the female patients. All cases of male breast cancer were histologically grade I ac- cording to Bloom’s classification; the histological grades were as follows for the female breast cancer cases: grade I in 99 patients, grade I1 in 87, and grade I11 in 55. The rates of hormone receptor positively were 89% for ER and 86% for PgR in male breast cancer, and 64% for ER and 44% for PgR in female breast cancer. Therefore, there was no significant differ- ence in the growth of male breast cancer and female breast cancer, but in male breast cancer the rate of hormone receptor positivity was high, endocrine therapy was effective, and the histological grade was low. Accordingly, the result following appropriate treatment of male breast cancer should be at least comparable to the results with female breast cancer.

KEY WORDS: histological malignancy, hormone receptor

INTRODUCTION Male breast cancer is rare and has been considered to

have a poorer prognosis than female breast cancer [ 1,2]. However, some recent reports demonstrated a more en- couraging prognosis for this disease [3]. We present 11 cases of male breast cancer and evaluate them with re- spect to tumor growth, hormone receptor status, and his- tological grade of the malignancy, in comparison with 241 female breast cancer cases.

MATERIALS AND METHODS From January 1961 to December 1986, 726 female

patients and 11 male patients were diagnosed as having breast cancer by the Second Department of Surgery, School of Medicine, Tokushima University. The inci-

dence was 1.5% for all patients with breast cancer. The 11 male patients with breast cancer were reviewed with respect to the stage and duration of symptoms, lymph node metastasis, hormone receptor status, and histolog- ical grade of the malignancy. The controls were 241 women who underwent radical operation for treatment of breast cancer.

The stage and histological type of each case were clas- sified into tumor, node, metastasis (TNM) categories us- ing the International Union Against Cancer (UICC) [4]

Accepted for publication March 23, 1990. Address reprint requests to Tadaoki Morimoto, MD. Second Depart- ment of Surgery, School of Medicine. The University of Tokushima, Kuramoto-cho 3, Tokushima 770, Japan.

0 1990 Wiley-Liss, Inc.

Cancer of the Male Breast 181 TABLE 1. Background Factors of Male Breast Cancer Cases*

-.

Hormone receptor Tumor Duration

Pat ic n t Chief size Stagins of symptoni Histological Nodal no.

I 51 Tumor 5.0 l l la 24 + NK Mucinous ca + - 82 Tumor 3.8 I 1 I20 + NK Invasive ductal ca with PIC 3 67 Tumor 3.5 IIIb S t lnvasive ductal c ; ~ + -1 61 Tumor 2.0 I 12 NK NK Mucinous ca -

S 53 Tumor I .s I 1.5 NK NK lnvasive ductal ca with PIC 6 S4 'Tumor (BNII) 1 . 1 1 2 Invasive ductal ca with PIC 7 69 Tumor I .6 I1 I + + lnvasive ductal ca + 8 69 Tumor I .6 I 12 + + lnvasive ductal ca 9 51 Tumor 3.8 IlIb 24 + + Invasive ductal ca +

10 75 Tumor 2.0 I 0.5 + + lnvasive ductal ca II 91 Tumor 3.0 I I 4 + + lnvasive ductal ca NK

"'Ahhr~viiition~: BND = bloody nipple discharge: NK - not known: PIC = predominant intraductal component: Ca = carcinoma

Age complaint (cm) (TN,M) (month) EK PgK t Y F involvement -

1 -

L

-

-

-

and World Health Organization (WHO) classifications [ 51, respectively. Hormone receptors were determined by a dextran-coated charcoal (DCC) technique, and the cutoff level for both estrogen receptors (EK) and proges- terone receptors (PgR) was defined as more than 5 fmoll mg protein. For the histological grade of the malignancy, the classification of Bloom was used [ 6 ] . Statistical sig- nificance was determined using the x' test and the Wilcoxon test.

RESULTS Male Breast Cancer Cases

Details 01' the 1 I male patients with breast cancer are given in 'pabks I , 11. and 111.

Age. The ages ranged from 5 1 to 9 1 years with median of 65.7 years.

Chief complaint. All of the patients became aware of the tumor as a subjective symptom, especially patient no. 6, who noticed a bloody discharge from the nipple when he became aware of the tumor.

The tumor was situated in the left breast in six patients and in the right breast in five patients. Also, it was located in the areola in eight patients. Patient no. 9 had a tumor that suggested Paget's disease of the nipple.

The maximum tumor di- ameter ranged from I . 1 to 5.0 cm. Patient no. 4 had three daughter nodules. The stage classification was stage I in five patients, stage I1 in three, stage IlIa in 1 , and stage l1Ib in two.

This ranged from half a month to 10 years, showing wide variation. However, it was within 2 years in all but one patient, who had the longest duration of I0 years.

The levels of ER and PgR were determined in nine and seven patients, respec- tively. The ER( +) and PgR( +) rates were 89% (8/9)

Location of tumor and primary site.

Tumor size and staging.

Duration of symptoms.

Hormone receptor status.

TABLE 11. Histological Grade of Malignancy in .Male Breast Cancer Cases (Classified According to Bloom)

Patient Tu bu 1 e Mitotic no. formation Pleomoruhism activity Grad(:

I 2 1 I I 2 I 1 1 I 3 I 2. 1 I 4 2 1 I I 5 2 I I I 6 2 I I I 7 8 9

I I I I I I

10 3 I I 1 I I 3 I I I

and 86% (6/7). The rate of EK( + ) PgR( + ) cases was 86% (617). with ER(-) PgR(-) being 14% (1/7). There were no ER( + ) PgR(-) or ER( - ) PgR( +) cases.

Histological type and nodal involvement. There were six cases of invasive ductal carcinoma, three of invasive ductal carcinoma with a predominant intraductal component, and two of mucinous carcinoma. The lymph nodes were not involved in six patients and involved in four.

In each case. there was variation in tubule formation, or one of thc three factors in the classification of Bloom, but mosi cases showed little pleomorphism or mitotic activity. On the basis of overall consideration of Bloom's three fac- tors. all patients were diagnosed as grade I with low malignancy.

All patients initially underwent radical operation. Four different mastectomy procedures were used: modified radical mastectomy in three patients, standard radical mastectomy in four, extended radical

Histological grade of malignancy.

Treatment.

182 Morimoto et al. TABLE Il l . Treatment and Outcome of Male Breast Cancer Cases*

Treatment

Patient Endocrine no. Mastectomy therapy Chemotherapy Radiotherapy Outcome Remarks

I

2

3 3

5

6

7

8

9

I 0

II

Standard Orchidectomy Adrenalectomy

Modified No

Extended NO Standard NO

Standard No

Modified Taniox i Fen

Extended Tamoxifen

Standard Tanoxifen

Extended Tamoxifen

Modified Tarnoxifen

Simple Tamoxifen ( Auchinclosh)

5 FU CPA

No

MMC MMC CPA Thio-TEPA Toyomycin MMC

MMC

MMC PI-207 NO

CPA

No

No

FI-207

Y O 5.000 rads

No

N o No

No

No

No

No

No

No

No

Died (8 years)

No rccurrence (8 years & 10 months)

Died (3 months) No recurrence ( 13 years

& 7 months)

Died (4 years & 6 months)

No recurrence (5 years & 1 month)

No recurrence (2 years & 10 months)

N o recurrence ( 2 years & 4 months)

No recurrence (2 years & 1 month)

No recurrence (I yea: & 7 months)

No recurrence (2 months)

Imcal recurrence Metastasis to hone

Metastasis to lung (Orchidectomy: PR)

(Adrenalcctomy: PR)

Renal failure

Acute pancreatitis

"Abbreviations: 5Fu = 5-fluorouracil; CPA = cyclophosphamide: MMC Mitomycin C; IT207 = Tegafur; PR = partial response.

mastectomy in three, and simple mastectomy in one. Ten of I 1 patients received postoperative adjuvant therapy, including endocrine therapy, chemotherapy , and radio- therapy. When patient no. 1 showed signs of recur- rence-that is, metastases to the bone and later to the lung-orchidectomy, and subsequently adrenalectomy were performed as surgical endocrine therapy.

Eight of the 1 I patients have shown no evidence of recurrence for periods ranging from 2 months to 13 years and 7 months after operation. Only patient no. 1 died of cancer, 8 years after surgery. Two other cases (no. 3 and no. 5 ) died 3 months and 4 years and 5 months after operation, respectively, although the cause of death was not cancer but renal failure (no. 3) and acute pancreatitis (no. 5 ) .

Prognosis.

Comparison Between Male and Female Breast Cancer

The duration of symptoms was 8.6 ? 9.1 months in men and 8.5 2 18.6 months in women. resulting in no significant difference between the sexes, as the Smirnov goodness-of-fit test excluded the male patient with a 10- year duration of symptoms.

The frequency of each stage was 46% for stage I , 27% for stage 11. 9% for stage IIIa, and 18% for stage IIIb in

male breast cancer, and 38% for stage I, 49% for stage 11, 6% for stage IIIa, and 3% for stage IIIb in female breast cancer. There was no significant difference in the distribution between sexes (Fig. 1 ) .

The frequency of no nodal involvement was 60% in male patients and 54% in female patients, again showing no significant difference (Fig. 2).

The rates of hormone receptor positivity were 89% for ER and 86% for PgR in male breast cancer, and 64% for ER and 44% for PgR in female breast cancer. The pos- itive rates for both ER and PgR were thus higher in male breast cancer than in female cancer, but the differences were not statistically significant (Table IV).

A11 1 1 cases of male breast cancer were histologically grade I according to Bloom's classification, whereas the histological grades of the female breast cancers were grade I in 99 patients (41%'1, grade I1 i n 87 (36%), and grade 111 in 55 (23%) (Table V).

DISCUSSION Male breast cancer is rare. The incidence is 0.28% to

2.4% of all cases of breast cancer in Japan 171; i t is about 1% in the West [8-10]. The incidence was 1.5% in our present hospital series and thus similar to the above- mentioned rates.

Cancer of the Male Breast 183

Male Breast Cancer

Female Breast Cancer

Male Breast Cancer

Female Breast Cancer

0 Stage ma

Stage mb

1 Stage N

Fig. 1 . Stages in male and female breast cancer (TNM classification)

Fig. 2. Nodal involvement i n male and female breast cancer.

TABLE IV. Hormone Receptor Status in Male and Female Breast Cancer

ER PgR

( + ) ( - ) ( + ) ( - )

-___ -

Mdk 89'h (8/9) ll'k (119) 86% (617) 14% (117) Female 64% (851112) 36'? (471132) 44% (541123) 56% (691123)

x? - I 65Q4 Fi\her P = 0 1666

x 2 = 3 2109 Fisher P = O 0482

TABLE V . Histological Grade of Malignancy in Male and Female Breast Cancer (Bloom's Classification) -

Male Female

Grade 1 Grade I1 Grade I l l Total

II 0 0

I 1

99 (4 1 %) 87 (36%) 55 (23%)

24 I

The prognosis has been considered to be poor, as the duration of symptoms is usually longer because of the patient's indifference, resulting in an advanced case; also, because local extention and nodal involvement are likely to occur in males because there is not so much encompassing mammary tissue [ I ] . However, a recent report demonstrated that the prognosis of male breast cancer was not necessarily poor 131.

The duration of symptoms in males was not signifi-

cantly longer than in females, and the frequency of each stage in males was also similar to that in females. In addition, there was no difference in nodal involvement between the sexes. The rate of hormone receptor posi- tivity tended to be higher in male breast cancer than in female breast cancer, but the smaller number of male breast cancer cases in this study prevented the assign- ment of a significant difference. All cases of male breast cancer were histologically classified as grade I. Thus, i t was concluded that the duration of symptoms and tumor growth in male breast cancer were similar to those in female breast cancer, but in male patients hormone re- ceptor positivity and histological differentiation of the tumors were higher.

The 5-year survival rate of the disease was very low (19%) in Wainwright's report of 1927 [ 121. However, the rates have been higher in subsequent studies: Holleb [ 131 and Heller [ 141 reported a 5-year survival rate of 42.7% and 72.096, respectively. The improved results may be due to greater awareness of male breast cancer and the development of endocrine therapy.

Some researchers have reported that ER( + ) breast cancer is characterized by biologically high differentia- tion and slow growth, but others have reported the con- trary; there are thus still conflicting views on this sub- ject. Previously, we reported [ IS] that the presence or absence of hormone receptors was not related to tumor

184 Morimoto et al. growth, although receptor status is useful in predicting the effects of endocrine therapy on female breast cancer.

In general, the ER positive rate for female breast can- cer is about 50% to 70% [ 161 and the rate was 64% in our female cases. On the other hand, Evenson [17] reported a ER positive rate of 85% (29/34) in male breast cancer, which was higher than in female breast cancer. Sonoo et al. [7] also found a high rate of receptor positivity, i.e., 85.6% (42.49), in male breast cancer. In this study, eight of nine tested cases (89%) were ER( + 1. Thus, endocrine therapy should be very effective in male breast cancer. The response rate to endocrine therapy in female breast cancer is reported to be about 50% in ER( +) patients and about 10% in ER(-) patients [16]. Sonoo et al. [7] reported response rates obtained by orchidectomy and adrenalectomy of 59.7% and 82.6%, respectively, show- ing high rates of effectiveness for this surgical endocrine therapy in male breast cancer. Patient no. 1 underwent orchidectomy and adrenalectomy at the time of me- tastases to bone and lung, respectively, and each treat- ment gained a good response. Six patients received ta- moxifen as postoperative adjuvant therapy and have shown no sign of recurrence to date.

No difference was found in tumor growth between the sexes, Endocrine therapy, however, is possibly more ef- fective in males, and the biological differentiation of the tumors is high; thus, results similar to those for female breast cancer can probably be achieved if appropriate treatment is administered.

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