Annals of Surgical Oncology

, 16:972

Men With Breast Cancer Have Same Disease-Specific and Event-Free Survival as Women

Authors

    • Department of SurgeryCRAN, Nancy-Université, CNRS, Centre Alexis Vautrin
  • Magalie Salou
    • Department of SurgeryCRAN, Nancy-Université, CNRS, Centre Alexis Vautrin
  • Christian Marchal
    • Department of RadiotherapyNancy-Université, Centre Alexis Vautrin, Regional Cancer Center
  • Anne Lesur
    • Department of SurgeryCRAN, Nancy-Université, CNRS, Centre Alexis Vautrin
  • Emmanuel Desandes
    • Department of BiostatisticsNancy-Université, Centre Alexis Vautrin, Regional Cancer Center
Breast Oncology

DOI: 10.1245/s10434-009-0327-6

Cite this article as:
Marchal, F., Salou, M., Marchal, C. et al. Ann Surg Oncol (2009) 16: 972. doi:10.1245/s10434-009-0327-6

Abstract

Background

Breast carcinoma in men is an uncommon disease. The aim of this study is to compare overall survival (OS) and disease-specific survival (DSS) in a group of matched men and women with breast cancer.

Methods

Each man with breast cancer recorded in the database was matched with two women. Matching was done based on age, year of diagnosis, and stage. To compare breast cancer characteristics between men and women, the chi-square test was used for qualitative data and the t-test for quantitative data. Overall survival and DSS were calculated using Kaplan-Meier methods. Cox proportional hazards models have been used to compare survival rates between men and women.

Results

The 58 male breast cancer patients were matched with 116 female patients. The mean age at diagnosis was 63.9 ± 11.9 years for men and 65.7 ± 11.5 years for women (P = .72). The median follow-up was 9.7 years for men and 10.7 years for women. The 5- and 10-year OS for men were, respectively, 58.9% and 33.9%. The 5- and 10-year OS for women were 68.2% and 52.1%. Men with breast cancer had a significant risk of dying compared with women (hazard ratio [HR] = 1.59; 95% confidence interval (95% CI), 1.04–2.42, P = .03). The 5- and 10-year DSS were 73.0% and 55.1% for men, and 72.8 and 61.2% for women, respectively. There was no difference in DSS between the two matched groups (HR = 1.26; 95% CI, 0.76–2.10, P = .37).

Conclusions

The prognosis for men with breast carcinoma is similar to that for women with similar-stage disease.

Male breast carcinoma (MBC) is rare: only 1500 cases are diagnosed in the United States each year.1 MBC accounts for 1% of all breast carcinoma, and 185 men will die of this disease in France.24 Clinical management of MBC is guided by research on the disease in women or by data from small case reports.3 Because of this low incidence, a limited number of patients are available for these studies.

Recent reviews using large databases or multi-institutional data, however, have increased the understanding of the natural history of breast cancer in men.5 It was long considered that male breast cancer carried a worse prognosis than that in women.68 These differences in prognosis were thought to result from delays in diagnosis rather than a different biological profile or tumor aggressiveness.911 The aim of this study was to compare the overall survival (OS), disease-specific survival (DSS), and event-free survival (EFS) in a group of carefully matched men and women with breast cancer.

Patients and Methods

Data for the current study were obtained from the prospective breast cancer database at the “Lorraine” Region Comprehensive Cancer Center (“Centre Alexis Vautrin” Vandoeuvre-les-Nancy, France). Institutional review board approval from our hospital was obtained. Only coded data without direct patient identifiers was used, to protect patient confidentiality. Each man with invasive breast cancer diagnosed between 1980 and 2002 and recorded in the database was carefully matched with two women. Male patients with carcinoma in situ or with history of other tumor were excluded of the study. Male patients who were operated on in another institution were also excluded. Matching was done based on age at diagnosis (within ± 5 years), year of diagnosis (within± 1 year) and stage of the primary cancer at the diagnosis. The women were chosen from a total of 7974 consecutive patients, recorded in the same database and who underwent treatment at our institution during the same period. When more than two women met the criteria for matching, the female patients whose year of diagnosis was closest to the male patient were chosen.

Status at the end of treatment, recurrence and type of recurrence, second breast cancer, time to follow-up, and status at most recent follow-up (alive with no evidence of disease, alive with disease, dead of disease, dead of other causes) were recorded. Follow-up information (cancer recurrence or relapse, death from treatment side effects or from the cancer itself, and second primary breast cancer) was obtained through an active search procedure in medical records or given by the liberal practitioners.

Potential prognostic factors included for each case were: the elements of American Joint Committee on Cancer (AJCC) stage (TNM), tumor grade SBR (Scarff-Bloom-Richardson), age at diagnosis, year of diagnosis, histologic type, estrogen receptor (ER) and progesterone receptor (PR) status, laterality, and tumor location.

To compare the breast cancer characteristics between men and women, the chi-square test was used for qualitative data and the t-test for quantitative data. Median length of follow-up was calculated using the inverse Kaplan-Meier method.12 Overall survival, DSS, and EFS were calculated using Kaplan-Meier methods.13 A survival analysis was performed on a data set containing all cases diagnosed between January 1, 1980 and December 31, 2002 and followed up until January 1, 2006. The end point for OS was death irrespective of the cause, death from cancer or from treatment side effects for DSS, death from cancer or from treatment side effects, and cancer recurrence for EFS, with the date of diagnosis acting as the time-origin. For EFS, patients with evolutive disease after the first induction phase were considered to have failed at day 0. Any variable unequally divided between the two matched groups (< .10) was also tested by multivariate analysis. Multivariate analyses were carried out using a Cox proportional hazard model, and the effect of gender on survival was estimated by hazard ratio (HR) and its 95% confidence interval (95% CI). P values < .05 were considered statistically significant. Statistical analysis was performed using SAS software (Version 8.02; SAS Institute, Cary, NC).

Results

The 58 male breast cancer patients were matched to 116 female patients during the same period. Table 1 displays the demographic and pathologic data of the matched male and female breast cancer patients. The mean age at diagnosis was equivalent for the two matched groups, 63.9 ± 11.9 years (range, 31.1–86.3) for men and 65.7 ± 11.5 years (range, 32.6–87.4) for women. There were significant differences noted for tumor location (P < .01) and hormone receptor status between men and women with breast cancer. Compared with women, more men had unknown tumor receptor status (29.3% versus 13.8% for ER and PR). Stage-specific treatment and use of multimodality therapy (surgery, radiotherapy, chemotherapy, and hormonotherapy) did not differ between the two matched groups.
Table 1

Characteristics of patients with breast carcinoma

 

Men (N = 58)

Women (N = 116)

P

Age at diagnosis (years)a

 Mean +/− std

63.9 ± 11.9

65.7 ± 11.5

0.72

 Median (range)

66.6 (31.1–86.3)

65.7 (32.6–87.4)

 

Year of diagnosisa

 1980–86

12 (20.7%)

24 (20.7%)

 

 1987–92

23 (39.7%)

46 (20.7%)

1.00

 1993–2002

23 (39.7%)

46 (20.7%)

 

Histologic type

 Invasive ductal carcinomas

50 (86.2%)

106 (91.4%)

 

 Another type

8 (13.8%)

10 (8.6%)

0.29

Tumor grade SBR

 1

3 (5.2%)

4 (3.4%)

 

 2

28 (48.3%)

72 (62.1%)

0.24

 3

21 (36.2%)

35 (30.2%)

 

 Unknown

6 (10.3%)

5 (4.3%)

 

ER status

 Positive

39 (67.2%)

83 (71.55%)

 

 Negative

2 (3.4%)

17 (14.7%)

<0.01

 Unknown

17 (29.3%)

16 (13.8%)

 

PR status

 Positive

35 (60.3%)

79 (68.1%)

 

 Negative

6 (10.3%)

21 (18.1%)

<0.03

 Unknown

17 (29.3%)

16 (13.8%)

 

Laterality

 Right

30 (51.7%)

57 (49.1%)

0.75

 Left

28 (48.3%)

59 (50.9%)

 

Tumor location

 Central

39 (67.2%)

23 (19.8%)

 

 Internal

9 (15.5%)

39 (33.6%)

<.01

 External

10 (17.2%)

54 (46.6%)

 

AJCC stagea

 I

14 (24.1%)

28 (24.1%)

 

 II

12 (20.7%)

24 (20.7%)

 

 III

27 (46.6%)

54 (46.6%)

1.00

 IV

5 (8.6%)

10 (8.6%)

 

aMatched criteria

STD standard deviation, SBR Scarff-Bloom–Richardson, ER estrogen receptor, PR progesterone receptor, AJCC American Joint Committee on Cancer

The median follow-up time for a 23-year study period was 9.7 years (range, 3.6–17.8) for men and 10.7 years (range, 2.5–17.8) for women (Table 2). Of the 58 men and 116 women with breast cancer, 37 deaths were reported among men [59.5%] were attributed to primary cancer (treatment side effects or the cancer itself)] and 54 deaths reported among women (75.9% were attributed to primary cancer). The 5- and 10-year OS for men were 58.9% (95% CI, 45.9–71.9) and 33.9% (95% CI, 20.2–47.6). The 5- and 10-year OS for women were 68.2% (95% CI, 59.6–76.8) and 52.1% (95% CI, 42.4–61.8). Men with breast cancer had a significant risk of dying compared with women (HR = 1.59; 95% CI, 1.04–2.42, P = .03) (Table 3).
Table 2

Outcome of men versus women with breast carcinoma

 

Men (N = 58)

Women (N = 116)

Status at the end of treatment

 Patients with nonevolutive disease

52 (89.7%)

95 (81.9%)

 Partial remission

0 (0%)

3 (2.6%)

 Stable disease

2 (3.45%)

0 (0%)

 Progression

4 (6.9%)

18 (15.5%)

Median follow-up years (range)

9.7 (3.6–17.8)

10.7 (2.5–17.8)

Status at the end of follow-up

 Alive

21 (36.2%)

62 (53.4%)

 Death

37 (63.8%)

54 (46.6%)

Status of disease when patient alive

 First total remission

21 (100%)

58 (93.5%)

 Second total remission

0 (0%)

2 (3.2%)

 Progression

0 (0%)

2 (3.2%)

Cause of death

 Breast cancer

21 (56.8%)

41 (75.9%)

 Complication of treatment

1 (2.7%)

0 (0%)

 Contralateral breast cancer

1 (2.7%)

1 (1.9%)

 Another cancer

6 (16.2%)

2 (3.7%)

 Another disease

8 (21.6%)

10 (18.5%)

Recurrence among complete responders

 No

35 (67.3%)

63 (66.3%)

 Yes

17 (32.7%)

32 (33.7%)

Type of recurrence among complete responders

 Local or regional

4 (7.7%)

4 (4.2%)

 Metastatic

13 (25%)

28 (29.4%)

Contralateral breast cancer

 No

57 (98.3%)

108 (93.1%)

 Yes

1 (1.7%)

8 (6.9%)

Table 3

Overall survival, disease-specific survival, and event-free survival of men versus women with breast carcinoma

 

Men (N = 58)

Women (N = 116)

HR (males vs females) [CI 95%] (unadjusted)

HR (males vs females) [CI 95%] (adjusteda)

Overall survival

 5 years

58.9% (45.9–71.9)

68.2% (59.6–76.8)

1.59 [1.05–2.42]

1.40 [0.87–2.25]

 10 years

33.9% (20.2–47.6)

52.1% (42.4–61.8)

  

Disease-specific survival

    

 5 years

73.0% (60.8–85.2)

72.8% (64.5–81.2)

1.27 [0.76–2.11]

1.06 [0.60–1.87]

 10 years

55.1% (39.4–70.8)

61.2% (51.5–70.9)

  

Event-free survival

    

 5 years

66.5% (53.7–79.3)

60.0% (50.9–69.1)

0.98 [0.60–1.59]

0.85 [0.49–1.46]

 10 years

46.2% (29.9–62.5)

53.8% (44.1–63.5)

  

HR hazard ratio, 95% CI 95% confidence interval

aAdjusted to ER status (positive vs negative or unknown), PR status (positive vs negative or unknown), and tumor location (central vs internal or external)

Among complete responders, recurrence rates were 32.7% for men and 33.7% for women. The proportions by type of recurrence were similar between men and women (Table 2). Among all cases included in the study, 1.7% of men and 6.9% of women had a contralateral breast cancer. The 5- and 10-year DSS were 73.0% (95% CI, 60.8–85.2) and 55.1% (95% CI, 39.4–70.8) for men, and 72.8% (95% CI, 64.5–81.2) and 61.2% (95% CI, 51.5–70.9) for women, respectively. The 5- and 10-year EFS were 66.5% (95% CI, 53.7–79.3) and 46.2% (95% CI, 29.9–62.5) for men, and 60.0% (95% CI, 50.9–69.1) and 53.8% (95% CI, 44.1–63.5) for women, respectively. There was no difference in DSS between the two matched groups (HR = 1.26; 95% CI, 0.76–2.10, P = .37). There was no difference in event-free survival between the two matched groups (HR = 0.97; 95% CI, 0.60–1.58, P = .91) (Table 3). Adjusted to ER status (positive versus negative or unknown), PR status (positive versus negative or unknown), and tumor location (central versus internal or external), no difference in survival was registered between men and women with breast carcinomas. Male breast cancer survivors had an increased risk of developing second primary cancers others than contralateral breast cancer, 12.1% and 5.2% for men and women, respectively (HR = 3.8, [95% CI, 1.2–12.1] P = .02). Second primary cancers were prostate carcinoma (3), rectal carcinoma (2), esophageal carcinoma (1), and lung carcinoma (1) for men. For women, endometrial carcinoma (2), ovarian carcinoma (1), pancreatic carcinoma (1), gastric carcinoma (1), and basocellular carcinoma were reported.

Discussion

For every 150 cases of female breast cancer, there is one case of male breast cancer. Since the late 1970 s, there has been a trend to a slight, 1.2% increase in male breast cancer incidence (both white and nonwhite, all ages), with observed values ranging from 0.5 to 1.6 per 100,000 per year.2 Although it remains a rare disease, the incidence of male breast carcinoma is increasing, with 26% increase in United States between 1973 and 1998.14 The worse prognosis for breast cancer in men has been attributed to the advanced stage at presentation due to a lack of awareness and a higher incidence of lymph node metastases.9,15,16

The disease-specific and event-free survival of the matched male and female breast cancer patients from our institution are similar, and overall survival is worse for men than for women. Several reports have tried to compare men breast cancer (MBC) and women breast cancer (WBC) features and prognosis (Table 4).1620 Many of these studies found more advanced tumors in men versus women. Men with breast cancer present higher-stage disease, larger tumors, and more lymph node positive disease.11 Women are more likely to be diagnosed with small early-stage tumors. Hill et al. studied the risk factors associated with an increased risk of breast cancer death (i.e., decreased survival), from 11 population-based cancer registries participating in the SEER (Surveillance, Epidemiology, and End Results) Program from 1973 to 2001.2 The most notable finding was that gender was not a significant predictor of survival after adjusting other variables, including stage at diagnosis. This finding supports some reports from smaller case series and gender comparison studies, but is in disagreement with the more recent publication by El-Tamer et al. that reported better survival among men compared with matched female controls.16,18,21 However, a small size together with a low proportion of stages III and IV were the limitation of El-Tamer’s series. It is a reason why in our study we matched one man with two women and significantly increased the proportion of stages III and IV, 7.5% and 55% for El-Tamer’s series and our series, respectively.18
Table 4

Survival rates reported in literature for matched men and women with breast cancer series

Author (years of publication)

Stage

Sex

Number of patients

Median follow -up (years)

Overall survival (%)

Disease specific survival (%)

Event-free survival (%)

     

5 years

10 years

5 years

10 years

5 years

10 years

Willsher (1997)16

 

M

41

3.5

55

50

  

F

123

4.2

67

49

Scott-Conner (1999)17

 

M

3627

      
 

0

  

82

97

 

I

  

78

98

 

II

  

68

88

 

III

  

51

67

 

IV

  

11

14

  

F

3627

      
 

0

  

93

100

 

I

  

85

98

 

II

  

70

81

 

 

III

  

56

66

 

IV

   

20

23

Meijer-van Gelder (2001)20

 

M

36

6.9

74

42

84

50

67

45

 

F

180

7

75

48

80

58

67

58

El-Tamer (2004)18

 

M

43

5.5

77

57

90

90

 

F

43

5.2

77

51

81

70

Our series (2008)

 

M

58

9.7

58.9

33.9

73

55.1

66.5

46.2

 

F

116

10.7

68.2

52.1

72.8

61.2

60

53.8

Many series reported a worse prognosis in men than in women, but several others did not find real differences when tumor stages and age were comparable in both populations.3 Borgen et al. matched 58 male patients with 174 WBC cases, with similar clinical and histopathological features.9 In both populations, a high proportion of male versus female breast cancer tumors < 2 cm was noted (71% versus 72%). After a 95-month median follow-up, survival did not differ significantly according to gender. Indeed, 10 years after diagnosis, 29% of male patients and 27% of female patients had died of breast cancer. Death resulting from other causes was 12% in men and 8% in women. After stratification by nodal status, the 10-year survival rates were nearly identical for men and women with negative nodes (76% versus 82%), whereas in patients with positive nodes, 49% of men and 58% of women survived. Willsher et al. matched 41 MBC cases with 123 WBC cases to allow comparison between EFS and OS.16 Age, mean tumor size, pathological grade, and axillary node status were comparable. However, a very high proportion of men (56%) did not undergo axillary dissection, and ipsilateral axillary node recurrence developed in 40% of the patients (versus 10% in women). Despite these results, with a 42-month median follow up for men and 50 months for women, the analysis did not show any significant difference in EFS and OS between the groups. The risk of local recurrence has been reported to be higher in men than in women, due to the small volume of breast tissue with easy access to lymphatics and direct extension to the muscles of the chest wall.22,23

A recent comparative analysis of patient outcome in men and women with breast cancer was carried out in British Columbia.24 In total, 60 cases of MBC (excluding T4 tumors) were compared with 4181 WBC cases over a 10-year period (1989–1998). In this study, locoregional recurrence rates were similar in men and women, 5% and 8.3%, respectively, with 3.85% and 1.1%, respectively, in our series. Similarly, 10-year actuarial distant relapse-free survival rates were 77% for men and 75% for women; breast cancer specific survival rates were 81% and 79% in the same respective groups. Actuarial OS rates were 75% and 53% for men and 82% and 65% for women (P = .11) at 5 and 10 years, respectively. Thus, this study found no evidence that gender is a prognostic factor. Because the randomized studies about radiotherapy after mastectomy confirmed that the improvement on locoregional control has a long-term impact on survival, the indications of adjuvant locoregional irradiation are more extensive for men with breast cancer than for women.3,2529 T3 and T4 tumors are clear indications for radiotherapy, along with the T2 tumors or T > 1 cm, because of the almost constant retroareolar topography in men.3,28,30 Radiotherapy could be one of the reasons for the amelioration of the prognosis of breast cancer in men.

Comorbid disease mortality is the major contributor to clinical outcome in men with breast cancer. The higher age at diagnosis for men than for women and the lack of breast cancer screening in men could explain this difference in OS between men and women. The mean age for man with breast cancer varied from 63 to 71 years old, 63.9 ± 11.9 years (range, 31.1–86.3) in our series.2,9,11,14,28,31 The cancer is diagnosed 5 to 10 years later than the second peak of frequency for women (60–63 years old), with a significant proportion of advanced tumor with derm or nipple invasion.11,15,20,31,32 Consequently, the impact of comorbidities and second neoplasm is more important and can induce confusion in comparative results. Globally, when MBC and WBC are compared at the same stage, the DSS rates are similar.2,11,16,17,20

In our series, male breast cancer survivors have an increased risk of developing second primary cancers other than contralateral breast cancer, 12.1% and 5.2% (P = .02) for men and women, respectively. In literature, men with a history of breast cancer had a 30-fold to 93-fold greater risk of contralateral breast cancer compared with twofold to fourfold risk among women with breast cancer.33,34 The risk for other cancers, including melanoma and prostate cancer, may also be elevated in male breast cancer survivors.1,33,35,36 More recently, Satram-Hoang et al. showed using the California Cancer Registry that men diagnosed with a first primary breast cancer have a 16% increased risk of developing a new primary cancer compared with men in the general population.37 Male breast cancer patients should be monitored carefully for the occurrence of second primary cancers, especially a second primary breast cancer.37

To our knowledge, this is one of the first studies of matched men and women with breast cancer with the longest follow-up.2,9,11,17,18 It allows the comparison with breast carcinoma in a homogeneous population of patients, where each man was carefully matched with two women. Limitations include the retrospective design of the study, the lack of detailed information regarding HER-2/neu overexpression and BRCA1 and BRCA2 mutations, and the inclusion of many patients with unknown hormone status.

In conclusion, survival rates of men and female with breast cancer are similar when age and stage of the disease are taken into consideration. However, comorbid disease mortality is likely the major contributor to clinical outcome in men with breast cancer.

Acknowledgments

Data were available thanks to the hospital-based cancer registry of Alexis Vautrin Center. We are grateful to Chantal Husson, Annette Walter, Sylvie Villa, Rosie Garcia-Gonzalez, Sophie Grandjean, and Marie-Claire Martin for technical assistance. We also thank Lina Bolotine for her assistance in writing the manuscript.

Copyright information

© Society of Surgical Oncology 2009