Cancer of the male breast: The Turkish experience

Journal of Surgical Oncology 53: 128-132 (1993)

Cancer of the Male Breast: The Turkish Experience

KAYIHAN ENCIN, MD, AND MUSTAFA UNSAL, MD

From the Center of Oncology and Nuclear Medicine, Okmeydani Hospital, Istanbul, Turkey

~

Twenty-six patients with male breast cancer who were admitted to the Center of Oncology and Nuclear Medicine, Istanbul, Turkey, between 1980 and 1988, were analyzed retrospectively. Median age was 60 years. Most lesions were infiltrating ductal carcinomas (92%). Of 26 lesions, 9 were staged as stage I1 (35%), 14 as stage I11 (54%), and 3 as stage IV (1 1%). All but five patients underwent unilateral mastectomy (81%). Post- operative treatment consisted of radiation therapy combined with chemotherapy in 11 patients (42%), chemotherapy with or without hormonal therapy in 4 (15%), radiation therapy alone in 10 (38%). Radiation therapy was delivered for a mean total radiation dose of 52 +- 2 Gy (range 30-60 Gy). Chemotherapy consisted of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in most patients (60%). FAC regimen (5-fluorouracil, Adriamycin, and cyclophosphamide) was given to 6 patients (40%). Six patients were known to have died of breast cancer during follow-up (23%). Fourteen patients were NED (no evidence of disease) at last follow-up (54%). Overall actuarial 5-year survival was calculated to be 37%, and median actuarial survival was 46.6 months. Actuarial 5-year disease- free survival was 2796, and median actuarial disease-free survival was 47.1 months. Only one patient had a local recurrence, and eight patients had 13 distant metastases (31%). Age (P = 0.023), tumor stage ( P = 0.055) and nodal status ( P = 0.013) were the most significant prognostic factors correlated with the overall survival. 0 1993 Wiley-Liss, Inc.

KEY WORDS: prognostic factors, male breast cancer, overall survival, radiation therapy, chemotherapy

INTRODUCTION Cancer of the male breast is a rare disease; it accounts

for approximately 1% of all breast cancer cases and for 1% of all malignant neoplasms in men [ 1-31. It is esti- mated by the American Cancer Society that 900 men in the United States are diagnosed as having breast cancer and that 300 die of this disease each year [4]. Most male breast cancer patients present with a unilateral mass, which is usually quite firm and painless. The principal differential diagnosis is with gynecomastia. Male breast cancer is evaluated and managed in a similar fashion to that for female breast cancer. The standard treatment of male breast cancer in most reported series has been radical or modified radical mastectomy. Adjuvant therapy has been radiation therapy, either preoperatively or, more

0 1993 Wiley-Liss, Inc.

commonly, postoperatively in most cases. The role of adjuvant systemic chemotherapy has not been clearly de- fined yet. Hormonal manipulation in patients with positive estrogen receptor protein has been reported to be encouraging [ 5 ] . Although some recent reports showed encouraging prognosis, it is generally believed that male breast cancer has a poorer prognosis than female breast cancer [6,7].

This study was undertaken to determine the situation of male breast cancer in Turkey and describes our experi-

Accepted for publication February 20, 1993. Dr. Kayihan Engin is currently at the Department of Radiation Oncol- ogy and Nuclear Medicine, Bodine Center for Cancer Treatment. Thomas Jefferson University, 1 1 1 S. 1 Ith Street, Philadelphia, PA 19107-5097. Address reprint requests there.

Male Breast Cancer 129

ence with 26 patients with male breast cancer who were treated in our institution from 1980 to 1988. The data assess their time of onset, age distribution, the histologi- cal types, axillary nodal status, and overall survival.

MATERIALS AND METHODS A retrospective review of patients with male breast

cancer was carried out at the Center of Oncology and Nuclear Medicine, Istanbul, Turkey. Twenty-six evalu- able cases treated in our center, between 1980 and 1988, were analyzed. Information relating to age, time and staging at clinical presentation, histopathology , surgical treatment, radiotherapy, and chemotherapy, and follow-up notes were collected. Staging was carried out using International Union Against Cancer (UICC), TNM, and stage groupings as the same staging criteria as applied to women with breast cancer [8].

Patient and pretreatment characteristics are shown in Table I. Median age was 60 years at the time of male breast cancer diagnosis (range 3 6 8 1 years). The great majority of the tumors were infiltrating ductal carcinomas (92%). One patient had tubular carcinoma, and one had papillary carcinoma (4%). The left breast was involved in 15 patients ( 5 8 % ) , and right breast in I 1 (42%). Patho- logic axillary lymph node status at diagnosis was determined in 21 patients (8 1%). Assessment of axillary status was performed clinically in others. Eight patients were node-negative (31%), and 18 node-positive (69%). Nine patients were staged as stage I1 (35%), 14 as stage I11 (54%), and 3 as stage IV ( I 1%). Staging was performed pathologically in the great majority of patients.

Treatment All but five patients underwent unilateral mastectomy

for male breast cancer (81%). Lesions were found to be inoperable in two patients. Three patients did not undergo further surgery after biopsy because of poor medical con- dition (two patients) and old age (one patient). Surgery consisted of' simple mastectomy, radical mastectomy, or modified radical mastectomy.

Postoperative treatment consisted of radiation therapy combined with chemotherapy in 11 patients (42%), chemotherapy with or without hormonal therapy in 4 (15%), and radiation therapy alone in 10 (38%). Three patients did not have any further treatment after surgery (12%).

Radiotherapy. Twenty-one patients were irradiated postoperatively in all but one case. In one patient, tumor was found to be inoperable and referred for primary radiation therapy. In another patient, radiation therapy could not be completed because of the development of lung metastasis during treatment. Radiation therapy was delivered to the chest wall by opposed tangential fields for a mean total radiation dose of 52 ? 2 Gy (range 30-60 Gy) over 5-6 weeks, using a 60Co machine. The axillary

apex, supraclavicular region, and internal mammarj nodes were also irradiated, generally to a total dose of

Chemotherapy. Adjuvant chemotherapy was given to 15 patients after surgery. Chemotherapy consisted of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in 9 patients (60%). FAC regimen (5-fluorouracil. Adriamycin, and cyclophosphamide) was given to 6 patients (40%). In some of these patients, hormonal therapy (tamoxifen) was added to the treatment. The number of chemotherapy cycles administered ranged between 6 and 12.

Survival was measured in years from the date of the completion of radiation treatment or surgery to the date of either death or last follow-up Unless otherwise noted, confidence intervals represent the standard error of the mean. The significance of the difference between means was determined by the Wilcoxon rank test.

Five-year actuarial overall survival (OS), and disease. free survival (DFS) were calculated. Survival curves were drawn using life-table survival analysis (Fig. 1).

45-50 Gy.

Method of analysis.

RESULTS Overall Survival

Locoregional control was achieved in 20 of 26 patients (77%). Six patients were known to have died of breast cancer during follow-up (23%). Fourteen patients were NED at last follow-up (54%). The other patients were lost to follow-up while on chemotherapy for either local recurrences or distant metastases. A second primary cancer (skin cancer) developed in one patient. Mean follow-up was 41.3 * 6.9 months (range 6.6147.7 months). Overall actuarial 5-year survival was calculated to be 37% and actuarial 5-year disease-free survival was 27% (Fig. 1). Median actuarial overall survival calculated by life-table survival analysis was 46.6 months (n = 26) and median actuarial disease-free survival was 47.1 months (n = 20).

Recurrences and Distant Metastases One patient had a local recurrence at 42.1 months and

was successfully salvaged with radiation treatment combined with chemotherapy. Three patients had one and five patients had two distant metastases, a total of eight patients with 13 distant metastases (31%) after treatment for male breast cancer. Mean time to distant metastasis was 29.3 ? 9.6 months (range 1.2-69.7 months). Bone was the most frequent distant site of metastasis (7, 54%), followed by lung ( 5 , 38%), and brain (1 , 8%).

Prognostic Factors Younger patients at the time of initial diagnosis

seemed to do significantly better. Mean overall survival

130 Engin and Unsal

TABLE I. Tumor and Treatment Characteristics and Outcome of 26 Male Breast Cancer Patients"

Distant Age Diagnosis Surgery Stage XRT Chemo. metastasis Outcome

56

69

72

81

60

50

64

71

60

78

54

68

62

59

64

63

46

36

41

48

52

61

57

62

Inf. ductal

lnf. ductal

lnf. ductal

Inf. ductal

Inf. ductal

Tubular

lnf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

lnf. ductal

lnf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

Papillary

Inf. ductal

Inf. ductal

Inf. ductal

Inf. ductal

RM

Bx

SM

Bx

Bx

RM

SM

SM

RM

SM

RM

SM

MRM

Bx

MRM

SM

SM

RM

SM

SM

SM

SM

Bx

SM

T2NOMO. Stage 11 T2N2M0, Stage IV T2NIM0,

T3N2M0, Stage Ill T4N2MI. Stage 1V

T3NOMO. Stage I11 T4N 1 MO, Stage I11

T3N2M0, Stage Ill

T2NlM0, Stage I1 T2NOM0, Stage 11 T3N I MO, Stage 111 T3N I MO, Stage I11 T3N I MO, Stage 111 T4NIMO. Stage 111 T3NOM0, Stage Ill T2NOM0,

T2NOM0, Stage II T2N2M0, Stage I11 T2NIM0, Stage II T2NOM0, Stage 11 T2NOMO. Stage 11 T4N2M0, Stage 111 T4NIMI, Stage IV T4N2M0, Stage I11

Stage I11

Stage II

60

-

-

-

18

55

-

60

60

50

50

50

50

50

50

30

50

50

50

60

50

50

~

60

-

FAC

-

FAC

FAC

FAC

FAC

-

CMF

-

CMF

CMF

CMF

-

CMF

-

CMF

CMF

-

-

-

-

FAC

CMF

-

-

-

-

Lung, bone

-

-

-

-

-

-

-

-

Bone

-

-

-

Brain, bone

Lung. bone

Lung, bone

Bone

-

Lung, bone

-

Alive, NED (35.1 months)

Died with disease (12.3 months)

Lost to follow-up (6.6 months)


Progression during XRT, lost to follow-up. metastatic disease ( I I . 1 months)


Local recurrence at 42.1 months (treated with XRT and CT), alive, NED (64.7 months)

Alive. NED (50.9 months)


Lost to follow-up, NED at last follow-up (20.4 months)




Died with disease ( I I .7 months)


Alive, NED ( 147.7 months)

Second primary at 80.1 months, alive, NED ( 1 17.0 months)

Lost to follow-up, metastatic disease (7 I .6 months)

Lost to follow-up, metastatic disease (62.7 months)




Died with disease (13. I months)

Lost to follow-up, NED at last follow-up (24.8 months)

corltirlued

Male Breast Cancer 131

TABLE I. Tumor and Treatment Characteristics and Outcome of 26 Male Breast Cancer Patients (Continued)*

Distant Age Diagnosis Surgery Stage XRT Chemo. metastasis Outcome

65 Inf. ductal SM T2NIMO. SO CMF

60 Inf. ductal SM T2N2M0, 50 -

Lost to follow-up, NED at last

Died with disease ( 1 8.7 months)

- Stage I1 follow-up (13.8 months)

Stage 111 Lung

'c Bx. biopsy alone; Chemo. chemotherapy; CMF, cyclophosphamide, methotrexate. fluorouracil; FAC, fluorouracil, Adriamycin. cyclophosphamide; Inf ductal, infiltrative ductal carcinoma; MRM. modified radical mastectomy; NED, no evidence of disease; papillary, papillary carcinoma; RM, radical mastectomy; SM, simple mastectomy; tubular, tubular carcinoma; XRT, radiation doses, Gy.

120

100

80

s 4 5 60 + a 2

40

20

n

.......... 11 -Disease-free Survival, 70 (n=20)

......... 1 +- Overall Survival, % ( ~ 2 6 )

I ...............................

0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 1 2 0 1 3 2

MONTHS

Fig. I . Actuarial overall survival (n = 26) and disease-free survival (n = 20) using life-table analysis in patients with male breast cancer. Median actuarial overall survival was 46.6 months, and median actuarial disease-free survival was 47. I months. Five-year overall survival was 37% and disease-free survival was 27%.

was 51.6 k 10.7 months (median of 50.8, range 11.7- 117.0 months) for patients <60 years old and 34.9 +- 8.8 months (median of 22.6, range 6.6-147.7 months) for patients 2 6 0 years old (P = 0.023).

Tumor stage at the time of initial diagnosis appeared to be a significant factor influencing overall survival. Stage I1 lesions did significantly better than the rest of the patients ( P = 0.055). Overall survival was 60.0 k 15.7 months (median of 39.8, range 14.8-147.7 months) for stage I1 patients and 31.4 t 5 . 5 inonths (median of 24.8, range 6 .671 .6 months) for stage 111 and IV patients.

Nodal status, performed pathologically in the great majority of patients at initial diagnosis, was the most significant prognostic factor correlated with overall sur-

vival. Overall survival was 67.3 5 16.3 months for patients with negative nodes (median of 57.8, range 19.9-- 147.7 months), while it was 29.8 ? 5.1 years for patients with positive nodes (median of 21.8, range 6.6-71.6 months), P = 0.013.

DISCUSSION The incidence of male carcinoma of the breast in the

tumor registries of our institution was consistent with other reported results and was less than 1% of all breast cancer cases, and less than 1% of all male cancers.

Geographic incidence of carcinoma of the breast paral- lels that of the female [9]. No association could be found between carcinoma of the male breast and race, geo- graphical location, marital status, occupation, or religion [ 101. Rare families have been reported in which several males have developed breast cancer [ll-131. No such case has been identified in our study.

Etiologic factors implicated in the development of male breast cancer include hyperestrogenism, Klinefelter syndrome, and radiation injury [ 1,16221. Patients with Klinefelter syndrome had a 6% incidence of breast cancer [22]. Breast cancer has also been reported in an XX male. The high incidence of male breast cancer in Egypt is attributed to its association with liver damage and hyperestrogenism caused by endemic schistosomiasis [ 151. This leads to the hypothesis that hyperestrogenism may be an etiologic factor in the development of breast cancer. Radiation exposure has been reported in some patients with male breast cancer [20,23]. The risk has been reported to be greater if exposure occurs at a younger age [24,25]. Patients developed breast cancer 12-36 years after the exposure.

The median age at which male breast cancer is diagnosed is reported to be several years later than in females [ 1,261. The median age was reported to be between 56 and 65 years and it was 60 years in our series.

Histopathological analyses reveal infiltrating ductal carcinoma in the majority of the cases as in females. It is reported that both the estrogen receptor protein and the progesteron receptor protein are present in male breast cancers in a higher percentage of patients than in females with breast carcinoma [27]. Data on hormone receptor

132 Engin and Unsal

protein status for patients in our series were not available. Patients with male breast cancer usually present with a more advanced disease than females [19,28]. The left breast is reported to be more commonly involved with cancer than right, with a ratio of I .07-1 [29]. The ratio was 1.36/1 in our series.

The overall 5-year survival rate was reported to be 49% in a review by Crichlow [ 11. I t was 79% in node-negative group and 28% in node-positive group. Nodal status was the most significant prognostic factor ( P = 0.013) in our series which is consistent with reported results. Actuarial 5-year overall survival was 37% and 5-year disease-free survival was 27% in the present study.

Although male breast cancer is an infrequently encoun- tered tumor, increased awareness. earlier detection and appropriate therapy may improve the outcome in these patients.

1.

2.

3.

4. 5.

6.

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8.

9.

10.

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Cancer of the male breast: The Turkish experience