1. Prognostic significance of tumor subtypes in male breast cancer:
a population-based study
Abstract # 1072
GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR
J.P. Leone1, J. Leone2, A.O. Zwenger2, J. Iturbe2, C.T. Vallejo2, B.A. Leone2
Background
Results
Male breast cancer (MaBC) is an uncommon disease representing less than 1% of all breast cancers in the United States. Although both male and female breast cancer patients (pts) have significantly improved their mortality and survival rates, the progress in men has lagged behind.
Information about prognostic factors and treatment strategies in MaBC is controversial, with most data extrapolated from female breast cancer.
The classification of breast cancer according to tumor subtypes has been one of the major achievements towards our knowledge of this neoplasm in women. This classification has been a challenge in MaBC; although this topic has gained much attention in recent years, few reports have described the incidence of each tumor subtype and its role in prognosis with significant discrepancies.
A better understanding of MaBC tumor subtypes would be critical to improve our assessment of prognosis and our treatment recommendations for these pts.
A total of 657 patients were included in this study. Median age was 65 years (range ). Median follow-up was 10 months (range 0-23). There were 34 deaths reported.
At diagnosis, 52% were 65 years or older, 82.6% were ductal, 46.4% were T1, 56.1% were N0, 7.6% were M1, 14% had breast conservation and 22% adjuvant radiotherapy. Median number of positive LNs was 0 (range 0-39).
Table 1 shows the patient characteristics according to tumor subtype. Patients with TN tumors were younger (p=0.007), had higher grade (p=0.0001), presented with more advanced stage (p=0.01), more likely to have a mastectomy (p=0.001) and to die from breast cancer (p=0.0003).
Unadjusted models revealed a decreased OS in those patients with stage IV (p<0.0001), T4 tumors (p=0.0081), M1 (p<0.0001), no surgery (p<0.0001), no radiation therapy (p=0.0347), ER- (p=0.0004), PR- (p=0.0002), HER2+ (p=0.04) and TN subtype (p<0.0001).
In multivariate analysis, patients who had no surgery, those with stage IV and those with TN tumors had a significantly worse OS.
Table 2. Univariate and Multivariate Analysis
Variable
Log-Rank P
Wald
Cox P HR
95.0% CI for HR
Lower
Upper
Stage
<0.0001
13.59
0.004 IV
Reference I
9.294
0.002
0.126
0.033
0.478 II
10.196
0.001
0.186
0.066
0.523
III
4.223
0.04
0.254
0.069
0.939
Surgery
10.042
0.007
No Surgery
Partial Mastectomy
3.395
0.065
0.219
0.043
1.102
Mastectomy
9.565
0.217
0.083
0.572
Radiation
0.0347
No Radiation
Adjuvant Radiation
1.605
0.205
0.434
0.119
1.578
Tumor Subtype
15.706
Triple Negative
HR+/HER2+
7.727
0.005
0.165
0.046
0.588
HR-/HER2+
1.264
0.261
0.281
0.031
2.572
HR+/HER2-
15.388
<0.001
0.104
0.034
0.323
Age at diagnosis
0.7006
Race
0.1425
Year of diagnosis
0.3746
Grade
0.1618
Histology
0.6715 T
0.0081 N
0.1095 M ER
0.0004 PR
0.0002
HER2
0.044
Marital status
0.3328
Table 1. Patient Characteristics
Tumor subtype:
HR+/
HER2-
HER2+
HR-/HER2+
Triple negative
Total N % P
All patients
552
84.0% 80
12.2% 8
1.2% 17
2.6%
657
Age at diagnosis, y
<50
50-64
>64 65
185
302
77.4%
80.1%
88.3% 11 38 31
13.1%
16.5%
9.1% 2 4
2.4%
0.9% 6 5
7.1%
1.5% 84
231
342
0.007
Race
White
Black
Other*
Unknown
454 27
84.7%
87.1%
100.0% 62 16
11.6%
19.0%
6.5%
0.0% 1
1.1%
3.2% 14
536
0.448
Year of diagnosis
2010
2011
258
294
82.2%
85.7% 47 33
15.0%
9.6%
1.3% 12
1.6%
3.5%
314
343
0.088
Histology
Ductal
Lobular
Other 87
83.6%
91.7%
85.3% 72 7
13.3%
8.3%
6.9% 3
2.9%
2.2%
4.9%
543
102
0.147
Grade I II
III/IV 81
293
155 23
95.3%
89.3%
72.8%
74.2% 32 37
4.7%
9.8%
17.4%
22.6%
0.3%
2.8% 15
0.6%
7.0% 85
328
213
<0.0001
Stage
III IV
218
189 97 35 13
90.1%
82.9%
81.5%
70.0%
72.2% 19 30
7.9%
13.2%
13.4%
22.0%
22.2%
1.8%
1.7%
2.0%
5.6%
2.1%
3.4%
6.0%
242
228
119 50 18
0.01
Surgery
No surgery
Partial mastectomy
Mastectomy 78
441
63.5%
84.8%
86.0% 9 57
26.9%
11.1%
5.8%
0.8%
3.8%
4.3% 52 92
513
0.001
Radiation
No radiation
Adjuvant radiation
432
120
84.4%
82.8% 61
11.9%
1.4%
2.5%
512
145
0.894
Vital status
Alive
Dead
531 21
85.2%
61.8%
23.5%
11.8%
623 34
Cause of Death
Breast cancer
45.0%
30.0%
14.3%
5.0%
20.0% 20
0.0003
Analysis of OS according to stage showed that pts with stage IV had significantly shorter survival (p<0.0001).
Objective
The aim of this population-based study was to analyze the characteristics of each tumor subtype in MaBC and its association with prognosis compared with other factors.
Materials and Methods
We obtained data from the National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) program, using the 18 registry ( ) database.
We extracted all cases of men with microscopically confirmed invasive breast cancer diagnosed between 2010 and 2011 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status. Pts with other primary either before or after breast cancer were excluded.
We analyzed the following variables: age at diagnosis, race, year of diagnosis, grade histology, ER, PR, HER2, T, N, M, stage, type of surgery, radiation therapy, laterality, number of lymph nodes (LN) examinined, number of positive LN, insurance, marital status, survival months, vital status and cause of death.
Tumor subtypes were classified as: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple negative (TN).
Pt characteristics were compared between tumor subtypes using chi2 or Fisher’s exact tests.
Survival probabilities were estimated using the Kaplan Meier method.
Log-Rank test analyzed differences in overall survival (OS) between groups.
Univariate and multivariate analyses were performed to determine the effect of each variable on OS.
OS was shorter for pts with HER2 positive tumors compared with those who had HER2 negative disease (p=0.044).
Conclusions
In this cohort, we observed significant differences in patient characteristics according to tumor subtype.
Most patients were diagnosed at age 65 or older and with early stages of disease.
Although HER2+ and TN patients represented a small proportion of cases, it is important to recognize their worse prognosis.
In addition to stage and surgery, tumor subtype has a clear influence on OS in MaBC.
Finally, analysis of OS according to tumor subtype showed significantly longer survival for pts with HR+/HER2- breast cancers (p<0.0001).
*American Indian/AK Native, Asian/Pacific Islander
1University of Iowa Holden Comprehensive Cancer Center, 2Grupo Oncológico Cooperativo del Sur