Original Article

Health promotion, disease prevention, and lifestyle

pISSN: 2287-4208 / eISSN: 2287-4690
World J Mens Health 2021 Jul 39(3): 506-515
https://doi.org/10.5534/wjmh.200164

Male Breast Cancer: A Comparative Analysis from

the National Cancer Database
Elizabeth B. Elimimian1 , Leah Elson1 , Hong Li2 , Hong Liang1 , Nadeem Bilani1 , Emily C. Zabor2,3 ,
Abby Statler3 , Zeina Nahleh1
1
Department of Hematology-Oncology, Maroone Cancer Center, Cleveland Clinic Florida, Weston, FL, 2Department of Quantitative Health
Sciences, Cleveland Clinic, 3Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

Purpose: Breast cancer (BC) in males accounts for <0.5% of all male cancer diagnoses and ~1% of all BCs in the United
States. We sought to describe clinicopathologic characteristics among male and female BC patients and differences in overall
survival (OS) through the National Cancer Database over 13 years (2004–2016).
Materials and Methods: Secondary to the 1:99 ratio of male to female BC cases, we randomly selected female cases for equal
comparison to males cases by diagnosis year. Chi-square and t-tests compared demographic and tumor characteristics. OS
was examined using Kaplan–Meier survival analysis.
Results: Among the ~2.7 million BC patients, 9 per 1,000 BCs were in males, the rate remained similar over time. The mean
(SD) age was 64.9±13.0 years for males and 60.7±13.6 years for females. Most of the male BC cases were white (non-Hispanic)
(n=19,015 [80.2%]), clinical stage I (n=7,353 [32.1%]) or stage II disease (n=7,923 [34.6%]), and tumors were moderate or
poorly differentiated (84.5%). Males exhibited more comorbidities, presented with a larger proportion of disease, and de-
creased OS (p<0.005) than females. Male OS was >10% lower at 5-years and nearly 20% lower at 10-years for males. More
males had primary BC tumors under the nipple; the 10-year OS rate for this site was 48.8%.
Conclusions: This study reports clinicopathologic characteristics of a large cohort of male BC. Males present at older age,
with a greater comorbidity index, at later stages of disease. Increased education regarding the continued risks of male breast
cancer may be warranted.

Keywords: Breast neoplasms, male; Epidemiology; Neoplasms; Patient-relative outcomes

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0)
which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

INTRODUCTION uncommon, its incidence is increasing [2,3]. Due to its

rarity, men with breast cancer have been largely un-
Currently, breast cancer in men accounts for <0.5% derrepresented in clinical trials and population studies.
of all male cancer diagnoses made annually, and con- At present time, no results from prospective national
stitutes approximately 1% of all breast cancer cases in or international clinical trials, solely focusing on male
the United States [1]. Although male breast cancer is breast cancer patients, have been reported. This pau-

Received: Sep 11, 2020 Accepted: Oct 15, 2020 Published online Dec 4, 2020
Correspondence to: Elizabeth B. Elimimian https://orcid.org/0000-0001-5168-5781
Department of Hematology-Oncology, Maroone Cancer Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331, USA.
Tel: +1-954-659-5840, Fax: +1-954-659-5810, E-mail: dr.elizabeth.elimimian@gmail.com
*Abstract selected for poster presentation at the 2019 San Antonio Breast Cancer Symposium.

Copyright © 2021 Korean Society for Sexual Medicine and Andrology

 Elizabeth B. Elimimian, et al: Male Breast Cancer: United States Study Population

city of male-specific information necessitates the use through stage IV breast cancer, diagnosed between
of results from clinical trials focused on ‘female’ breast 2004 and 2016. The International Classification of Dis-
cancer patients to inform disease management. As ease for Oncology (ICD-O3) codes were used to classify
such, the treatment of male breast cancer patients pre- histologic information. The base population included
dominantly mirrors that of postmenopausal women [4]. n=2,696,734 primary cases of male and female breast
While breast cancer represents a relatively small cancer patients. Overall, 23,990 male patients were
proportion of all diagnosed cancers among men, it is included in our analyses. Because of an approximate
associated with one of the highest mortality rates. In 1:99 ratio of male to female patients included within
2019, the American Cancer Society reported that more the dataset, the same number of female breast cancer
than three times as many men will be diagnosed with patients as male breast cancer patients, in each diag-
testicular cancer than with breast cancer. However, nosis year, were randomly selected for this study using
paradoxically, over the last five years, more men have simple random sample method.
died from breast cancer than testicular cancer [5,6].
These reported findings underscore the importance 2. Statistical considerations
of continuing research for male-specific breast cancer. Chi-square and t-tests, where appropriate, were used
Therefore, population-based studies may be helpful to compare demographic and clinical characteristics
in providing significant insight into these rare tumor between the male and sampled female group, includ-
types, and may assist in the subsequent development ing: categorical age (<50 years, 50–69 years, ≥70 years),
of treatment guidelines and recommendations. race (white, black, Hispanic, Asian, and other including
Using a large dataset extracted from the National Pacific Islander, Native American, and other races),
Cancer Database (NCDB), we sought to investigate the insurance type (not insured, private insurance, Medic-
demographic and clinical differences between male vs. aid, Medicare, other government), categorical income
female breast cancer patients, and how these differenc- (<$30,000, $30,000–34,999, $35,000–45,999, ≥$46,000),
es may contribute to disparities in overall survival (OS). area of residence (metro, urban, rural), clinical staging
We also sought to further explore the mortality gap (0, I, II, III, IV), disease grade (well differentiated, mod-
between male and female patients with breast cancer. erately differentiated, poorly/undifferentiated), location
of tumor at breast (“primary tumor site”: axillary tail,
MATERIALS AND METHODS upper-outer quadrant, upper-inner quadrant, central/
nipple, lower-outer quadrant, lower-inner quadrant,
1. Subject and ethics statement overlapping), invasive behavior (yes or no), estrogen
After obtaining Cleveland Clinic Institutional Re- receptor (ER+) status (yes or no), progesterone recep-
view Board (IRB) approval (No. FLA 19-044), we con- tor (PR+) status (yes or no), human epidermal growth
ducted a retrospective analysis of male and female factor receptor 2 (HER2+) status (yes or no), and Charl-
patients diagnosed with breast cancer between 2004 son–Deyo comorbidity score (0, 1, 2, ≥3). All variables
and 2016, as reported to the NCDB. Male and female included less than 10% of missing data, except for
designations were made based upon biological sex. The grade (11.7%) and HER2 status (52.2% overall; ~3% af-
NCDB is a United States cancer registry that serves as ter 2010). HER2 status was not widely reported to the
a repository for cancer diagnoses and clinical outcomes. NCDB until after 2009. Follow-up time was calculated
Information in the NCDB represents more than 1,500 from the date of diagnosis to the date of death or last
medical facilities utilizing standardized reporting mea- alive contact, and patients still alive were censored for
sures approved by the Commission on Cancer and the OS. The Kaplan–Meier method estimated OS accord-
American College of Surgeons [7]. Currently, the NCDB ing to sex, and the log-rank test was used to compare
captures more than 70% of cancer cases diagnosed in sexes. Both 5-year and 10-year survival estimates are
the United States [7]. Access to the NCDB registry presented.
was achieved based on a Participant User File award Multivariable analyses using Cox proportional
granted to the principal investigator (Z.N.). hazard models were conducted to understand which
Using the NCDB dataset, we identified both female demographic and clinical factors were independently
and male breast cancer patients with TNM Stage 0 associated with survivorship, in both male and female

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Table 1. Baseline characteristics of study population

Variable Total No. of subject Male (n=23,990) Female (n=23,990) p-value
Age at diagnosis (y) 47,980 64.9±13.0 60.7±13.6 <0.001
<50 3,150 (13.1) 5,410 (22.6)
50–70 12,378 (51.6) 12,574 (52.4)
≥70 8,462 (35.3) 6,006 (25.0)
Race 47,465 <0.001
White 19,015 (80.2) 18,686 (78.7)
Black 3,123 (13.2) 2,861 (12.0)
Hispanic 881 (3.7) 1,274 (5.4)
Asian 499 (2.1) 746 (3.1)
Other 194 (0.8) 186 (0.78)
Insurance 47,096 <0.001
Not insured 566 (2.4) 466 (2.0)
Private insurance/managed care 10,244 (43.6) 12,719 (53.9)
Medicaid 1,032 (4.4) 1,408 (6.0)
Medicare 11,301 (48.1) 8,744 (37.1)
Other government 357 (1.5) 259 (1.1)
Income 46,514 <0.001
<$30,000 2,742 (11.8) 2,432 (10.4)
$30,000–34,999 3,671 (15.8) 3,501 (15.0)
$35,000–45,999 6,197 (26.7) 6,272 (26.9)
≥$46,000 10,630 (45.7) 11,069 (47.6)
Area of residence 47,980 0.008
Metro 19,982 (83.3) 20,232 (84.3)
Urban 2,975 (12.4) 2,793 (11.6)
Rural 1,033 (4.3) 965 (4.0)
Clinical staging 46,107 <0.001
Stage 0 2,914 (12.7) 4,697 (20.3)
Stage I 7,353 (32.1) 9,674 (41.7)
Stage II 7,923 (34.6) 5,837 (25.2)
Stage III 3,267 (14.3) 2,049 (8.8)
Stage IV 1,461 (6.4) 932 (4.0)
Grade 42,364 <0.001
Well differentiated 3,307 (15.5) 4,514 (21.5)
Moderately differentiated 10,658 (50.0) 9,238 (43.9)
Poorly or undifferentiated 7,360 (34.5) 7,287 (34.6)
Ductal histology 47,980 17,971 (74.9) 16,035 (66.8) <0.001
Primary tumor site 47,980 <0.001
Axillary tail 57 (0.24) 103 (0.43)
Upper-outer quadrant 4,082 (17.0) 7,941 (33.1)
Upper-inner quadrant 1,238 (5.2) 2,581 (10.8)
Central/nipple 7,879 (32.8) 1,385 (5.8)
Lower-outer quadrant 974 (4.1) 1,674 (7.0)
Lower-inner quadrant 643 (2.7) 1,327 (5.5)
Overlapping/NOS 9,117 (38.0) 8,979 (37.4)
Invasive behavior 47,980 21,008 (87.6) 19,264 (80.3) <0.001
ER+ 44,398 20,432 (92.1) 18,025 (81.2) <0.001
PR+ 43,888 18,261 (83.1) 15,520 (70.8) <0.001
HER2+ (available 2010 or later) 22,928 1,481 (12.4) 1,564 (14.2) <0.001

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Table 1. Continued.
Variable Total No. of subject Male (n=23,990) Female (n=23,990) p-value
Charlson–Deyo score 47,980 <0.001
0 18,888 (78.7) 20,387 (85.0)
1 3,741(15.6) 2,842 (11.8)
2 976 (4.1) 562 (2.3)
≥3 385 (1.6) 199 (0.83)
Values are presented as number only, mean±standard deviation, or number (%).
NOS: not otherwise specified, ER+: estrogen receptor, PR+: progesterone receptor, HER2+: human epidermal growth factor receptor 2.

groups. Independent factors were identified from de-

mographic and clinical factors listed in Table 1 (except Male vs. female primary BC sites

for HER2 receptor status) using stepwise model selec-

tion procedures with significance level of p<0.01 as Axillary Axillary
tail of
entry-criteria and p<0.001 as stay-criteria, due to the
tail of Male Female
breast <1% <1% breast
Upper-inner quadrant
large sample size. For the first model, the hazard ratio
(HR) for male compared to female was initially esti- Upper-outer 17%
quadrant
5% 11%
33%
Upper-outer
quadrant
mated using the inclusion of age, clinical staging, and 6%
Charlson–Deyo comorbidity score. For the next sub- Lower-outer 4% 3% 6% 7% Lower-outer
sequent model, independent predictors were included quadrant quadrant

with demonstrated impact on OS. Lower-inner quadrant

Due to biological differences, a gender stratified anal-

Overlapping lesion 38% Overlapping lesion 37%

ysis was performed to identify common and uncommon Fig. 1. Primary breast cancer (BC) tumor site, stratified by sex.
predictors in both the male and female groups.
All statistical analyses were conducted with SAS scores. In addition, the distribution of primary tumor
ver. 9.4 (SAS Institute Inc. Cary, NC, USA). Two-sided site was different between male and females groups:
p-values are presented, p<0.001 is considered as signifi- with males exhibiting more central/nipple disease ten-
cant. dency (32.8% vs. 5.8%), and females exhibiting more up-
per-outer quadrant disease tendency (33.1% vs. 17.0%).
RESULTS There were similar rates of primary tumors with over-
lapping sites (Fig. 1). The male group also demonstrated
A total study population of 47,980 (23,990 males and a lower rate of private insurance coverage compared
23,990 females) was included in our analyses. Male and with the female group. Male breast cancer patients
female median (interquartile range) follow-up time presented more frequently with ER+ (92.1% vs. 81.2%,
from diagnosis to death or last contact was 4.0 years p<0.001) and PR+ (83.1% vs. 70.8%, p<0.001) disease than
(1.9–6.9) and 4.7 years (2.3–7.7), respectively. Compara- female patients (Table 1).
tive demographic and clinical characteristics between Notably, males exhibited significantly worse OS
groups are presented in Table 1. (p<0.001) than females. The 5-year OS was 72.8% in
Univariate analyses (Table 1) showed that the follow- males vs. 83.4% in females, and the 10-year survival
ing demographic and clinical characteristics were sig- was 52.5% in males vs. 69.1% in females (Fig. 2A). Ad-
nificantly different (p<0.001) according to sex: age, race, ditionally, the median OS was 10.7 years for the male
insurance status, income, clinical staging, Charlson– group, but the median survival for the female group
Deyo comorbidity score, disease grade, primary tumor was not reached. The unadjusted hazard of early death
site, invasive behavior, ER+ status, and PR+ status. was 75% higher (unadjusted HR, 1.75; 95% confidence
Of note at diagnosis, male patients were older, present interval [CI], 1.69–1.82) in males than in females (Fig.
with later clinical staging, exhibit worse disease grade, 2B). In a stepwise, multivariable model, after adjusting
had more ductal histology, and worse comorbidity for age, clinical stage, and Charlson–Deyo comorbid-

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A B
100

83.4 1.75 (1.69 1.82)

75 Unadjusted
Overall survival (%)

69.1
72.8

50
52.5
1.25 (1.20 1.30)
a
25 Male Adjusted
Female
p (logrank) <0.001
0
0 5 10 15 1.00 1.25 1.50 1.75 2.00
Years from diagnosis Hazard ratio (95% CI)
Fig. 2. (A) Comparison of overall survival (OS) in male and female breast cancer; numbers indicate % OS at 5-years and 10-years in each group. (B)
Hazard ratio of death for male vs. female patients (adjusted and unadjusted). aAdjusted for age, clinical stage, and Charlson–Deyo comorbidity
score. CI: confidence interval.

ity score, with 87.5% of the study sample, the hazard early death, in both males and females, were: late clini-
of early death was still observed to be higher in the cal stage, older age, and Charlson–Deyo score. Other
male group (adjusted HR, 1.25; 95% CI, 1.20–1.30) (Fig. factors associated with early death for both males and
2B). These results remained the same (adjusted HR, females included: being African American, having low
1.28; 95% CI, 1.21–1.35) when expanding the analyses income, using Medicaid insurance type, and presenting
to a second, stepwise multivariable model to include with poorer grade. With respect to uncommon factors,
additional independent protectors identified from this primary tumor site was associated with early death for
study and reported elsewhere, including: race, income, males only (Table 2).
insurance type, grade, and both ER+ and PR+ status,
in addition to the primary tumor site, which has been DISCUSSION
uniquely identified from this study with 70% of the
study sample (Table 2). The age (mean, 62.9 vs. 62.2 This analysis represents one of the largest studies
years old), clinical staging (III or IV) (16.5% vs. 17.4%), evaluating demographic characteristics, clinical charac-
and grade 3 (34.6% vs. 34.2%) were similar between pa- teristics, and survival outcomes associated with gender
tients included in multivariate analysis and those who disparities among patients with breast cancer. Similar
were excluded. The 5-year (70.8% vs. 75.6%–84.9%) and to previous reports, patients with male breast cancer
the 10-year (48.8% vs. 58.4%–69.2%) OS for primary tu- were more likely to have ER+ and PR+ tumors, ductal
mors originating under the nipple or the central breast histology, and present at later stages of disease, com-
location, was the worst compared to all other locations pared to female patients with breast cancer [8-11]. Sur-
(Table 3). vival analyses in this study indicated that males with
Owing to the inherent biological differences between breast cancer have an observed survival disadvantage
meles and females, multivariable analyses were next when compared to their female counterparts, demon-
stratified by gender. All variables listed in Table 1 (ex- strating significantly poorer 5-year and 10-year OS.
cept HER2+ status data, which was not available until These results may be partially explained by indepen-
after 2009) were included in the analyses to identify dent factor analyses indicating that males were found
factors independently associated with OS separately to be older at diagnosis (mean age 64.9 years for males
for males and females (Table 2). Due to variance in vs. 60.7 years for females), present with later stages of
completeness of data, the final multivariable model in- disease, exhibit different primary tumor location, and
cluded 70% of the study population for both males and experience different disease management, when com-
females after excluding cases with missing values. The pared with females.
top three factors identified as being associated with These findings corroborate earlier studies, which also

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Table 2. Factors independently associated with OS in male and female

Male Female
KM OS (%) Cox multivariable KM OS (%) Cox multivariable
Variable  No. of  No. of
subject 5-year OS 5-year OS
HR (95% CI) p-value subject HR (95% CI) p-value 
(95% CI)  (95% CI) 
Stage
Stage 0 2,679 89.6 (88.3–91.0) 1   4,312 93.9 (93.0–94.7) 1  
Stage I 6,665 83.7 (82.7–84.7) 1.36 (1.15–1.60) <0.001 8,744 89.1 (88.4–89.9) 1.57 (1.34–1.83) <0.001
Stage II 7,205 73.2 (72.0–74.4) 2.06 (1.76–2.42) <0.001 5,355 82.3 (81.1–83.4) 2.46 (2.11–2.86) <0.001
Stage III 3,003 58.1 (56.1–60.2) 3.38 (2.88–3.98) <0.001 1,891 67.1 (64.8–69.5) 4.85 (4.13–5.71) <0.001
Stage IV 1,313 19.8 (17.3–22.3) 12.26 (10.33–14.55) <0.001 819 23.5 (20.1–26.9) 17.38 (14.61–20.68) <0.001
Age (y)            
<50 2,917 84.1 (82.5–85.6) 1   4,997 90.7 (89.8–91.7) 1  
50–70 11,257 80.4 (79.5–81.2) 1.20 (1.07–1.35)  0.002 11,432 88.1 (87.4–88.8) 1.40 (1.24–1.58) <0.001
≥70 7,712 57.8 (56.5–59.1) 2.64 (2.32–3.01) <0.001 5,471 67.3 (65.9–68.7) 3.65 (3.17–4.20) <0.001
Charlson–Deyo score            
0 17,245 76.8 (76.0–77.5) 1   18,637 85.4 (84.8–85.9) 1  
1 3,444 63.6 (61.7–65.5) 1.49 (1.39–1.60) <0.001 2,590 75.9 (74.0–77.8) 1.29 (1.17–1.42) <0.001
2 884 46.6 (42.8–50.4) 2.34 (2.09–2.61) <0.001 508 60.7 (55.9–65.6) 2.09 (1.78–2.46) <0.001
≥3 313 32.0 (25.9–38.0) 2.71 (2.31–3.19) <0.001 165 45.5 (36.9–54.1) 3.56 (2.80–4.52) <0.001
Insurance type            
Not insured 531 67.7 (62.9–72.4) 1.55 (1.27–1.88) <0.001 437 76.8 (72.3–81.3) 1.40 (1.06–1.83) 0.016
Private 9,399 84.2 (83.4–85.1) 1   11,684 90.6 (90.0–91.2) 1  
Medicaid 927 67.4 (63.7–71.0) 1.72 (1.48–1.99) <0.001 1,266 80.4 (77.9–83.0) 1.68 (1.44–1.97) <0.001
Medicare 10,256 63.3 (62.2–64.4) 1.53 (1.41–1.65) <0.001 7,898 73.6 (72.5–74.7) 1.50 (1.35–1.66) <0.001
Other government 312 67.7 (61.2–74.3) 1.45 (1.11–1.90)  0.007 239 90.5 (86.3–94.8) 1.12 (0.71–1.77) 0.62
Grade            
1 3,023 83.0 (81.5–84.6) 1   4,121 88.9 (87.8–90.0) 1  
2 9,633 75.3 (74.3–76.3) 1.13 (1.03–1.25)  0.011 8,339 84.9 (84.0–85.8) 1.1113 (1.0005–1.2345) 0.049
3 6,735 65.9 (64.6–67.2) 1.41 (1.27–1.55) <0.001 6,661 78.6 (77.5–79.8) 1.32 (1.17–1.48) <0.001
Race            
White 17,403 72.8 (72.0–73.5) 1   17,146 83.6 (83.0–84.3) 1  
Black 2,798 68.3 (66.3–70.4) 1.05 (0.96–1.15) 0.28 2,571 77.1 (75.2–78.9) 1.15 (1.03–1.28) 0.012
Hispanic 805 80.7 (77.4–84.0) 0.66 (0.55–0.80) <0.001 1,133 88.1 (85.9–90.4) 0.70 (0.58–0.86) <0.001
Asian 447 80.8 (76.3–85.2) 0.755 (0.576–0.988) 0.041 669 90.6 (87.9–93.3) 0.63 (0.47–0.84) 0.002
Other 170 79.5 (71.9–87.1) 0.81 (0.53–1.24) 0.34 164 88.8 (83.1–94.5) 0.72 (0.41–1.27) 0.26
Income            
<$30,000 2,510 66.7 (64.5–68.8) 1.29 (1.18–1.42) <0.001 2,192 76.5 (74.4–78.5) 1.19 (1.05–1.33) 0.004
$30,000–$34,999 3314 67.3 (65.4–69.2) 1.28 (1.18–1.38) <0.001 3,203 80.4 (78.8–82.0) 1.13 (1.02–1.26) 0.016
$35,000–$45,999 5,645 72.4 (71.1–73.8) 1.12 (1.04–1.20) 0.002 5,748 81.8 (80.7–83.0) 1.02 (0.94–1.12) 0.59
≥$46,000 9,733 76.3 (75.4–77.3) 1   10,095 86.4 (85.7–87.2) 1  
PR status    
Negative 3,424 66.4 (64.6–68.2) 1.27 (1.18–1.36) <0.001 -   -  -   -
Positive 16,515 74.1 (73.3–74.9) 1 -   -  -   -
ER status    
Negative -  -  -  - 3,826 76.2 (74.7–77.7) 1.39 (1.26–1.52) <0.001
Positive -   -  -  - 16,360 85.1 (84.4–85.7) 1  

report the median age for male breast cancer patients toxicity of systemic or radiotherapies. Additionally, age
to be in the 60s [2,12-14]. Older patients exhibit a higher related-immune dysfunction/immunosenescence results
variability of health, and may be less resilient to the in an abnormal prolongation of inflammatory reactions

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Table 2. Continued
Male Female
KM OS (%) Cox multivariable KM OS (%) Cox multivariable
Variable  No. of  No. of
subject 5-year OS 5-year OS
HR (95% CI) p-value subject HR (95% CI) p-value 
(95% CI)  (95% CI) 
Primary BC site    
Axillary tail 52 75.9 (63.2–88.5) 0.65 (0.33–1.31) 0.23 -   -  -  - 
Upper-outer quadrant 3,711 79.2 (77.7–80.8) 0.911 (0.833–0.998) 0.044 -   -  -  - 
Upper-inner quadrant 1,112 82.4 (79.8–85.0) 0.80 (0.68–0.93) 0.004 -   -  -  - 
Central/nipple 7,104 69.0 (67.8–70.3) 1 -   -  -  - 
Lower-outer quadrant 879 83.2 (80.3–86.1) 0.77 (0.65–0.92) 0.003 -   -  -  - 
Lower-inner quadrant 574 81.5 (77.8–85.2) 0.77 (0.63–0.94) 0.010  -  -  -  - 
Overlapping/NOS 8,454 70.2 (69.1–71.4) 0.98 (0.92–1.05) 0.65 -    -   -   - 
OS: overall survival, KM: Kaplan–Meier, CI: confidence interval, HR: hazard ratio, PR+: progesterone receptor, ER+: estrogen receptor, BC: breast
cancer, NOS: not otherwise specified, -: not available.

Table 3. Overall survival and primary breast cancer site (p<0.001) that factors beyond age and staging may also contrib-
% of 5-year survival % of 10-year survival ute to the survival disparities noted here. In fact, in
Primary site
(95% CI) (95% CI) this study, after adjusting for age, clinical stage, and
Overall 78.1 (77.7–78.6) 60.9 (60.2–61.6) comorbidity index, the risk of death for breast cancer
Axillary tail 79.7 (72.7–86.6) 63.8 (52.9–74.8) among male patients decreased by 50%, but male were
UO quadrant 83.2 (82.4–84.0) 68.9 (67.6–70.2) ‘still’ observed to exhibit a significantly higher risk of
UI quadrant 84.9 (83.5–86.3) 69.2 (66.6–71.8) death than female.
Central/nipple 70.8 (69.6–71.9) 48.8 (47.0–50.5) Sex-based survival differences may also be due to
LO quadrant 84.0 (82.2–85.7) 68.3 (65.2–71.3) primary tumor site. Among the unique observations
LI quadrant 84.2 (82.2–86.1) 67.1 (63.7–70.5)
of our analyses, is the effect of primary tumor site
Overlapping 75.6 (74.8–76.3) 58.4 (57.2–59.6)
on breast cancer mortality, stratified by gender. Male
CI: confidence interval, UO: upper-outer, UI: upper-inner, LO: lower-
with breast cancer had more tumors diagnosed under
outer, LI: lower-inner.
the nipple/central breast area (33%) compared to fe-
which may actually promote the progression or devel- male with breast cancer (6%). This clinicopathologic
opment of cancer [15]. In elderly patients, the immune difference may contribute to the adverse prognoses
system produces myeloid cells from the bone marrow observed in male, as the 5-year OS for centrally-located
at an increased frequency and subsequently decreases breast cancers was significantly worse than tumors in
B and T cell progenitors [15]. Exposure to chemother- the upper outer quadrant of the breast (71% vs. 83%,
apy can accelerate these processes, making older pa- respectively). Similarly, at 10 years, the OS for nipple/
tients more vulnerable to infection and chemotherapy- central tumors was significantly worse than the sur-
induced side effects [16]. Clinical trials which evaluate vival rate for tumors in the upper-outer quadrant (49%
male breast cancer patients, stratified by age, would vs. 69%, respectively). Unlike clinical grade, lymph node
further the understanding of chemotherapy-dependent involvement, and hormone receptors and HER2 status,
effects in elderly patients, at the cellular level. primary breast tumor location is not widely regarded
Another possible contributing factor to the mortal- as a prognostic factor. However, several studies have
ity differences noted between sex is the differences in reported ‘some’ association between breast tumor loca-
stage at diagnosis. Our analyses revealed that male tion and OS. An analysis of 305,443 female with breast
patients were diagnosed with later stage breast cancer, cancer, as recorded in the SEER database between 1990
compared to female patients, a trend widely supported and 2009, found that mortality was increased for pri-
in the literature [8-11]. However, mortality differences mary tumors in the left central portion of the breast
between genders have been observed, even in early as well as the left and right lower outer quadrants [18].
stages of breast cancer [17]. This supports the notion Similar studies found that breast tumors in the me-

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 Elizabeth B. Elimimian, et al: Male Breast Cancer: United States Study Population

dial breast adversely impacted OS [19]. Although these have decreased significantly [25]. In fact, the female
studies focused on a smaller population of patients and breast cancer death rate reached its peak in 1989, and
included only females, our analyses adds to the existing has been steadily declining in the years since [5], attrib-
literature and further suggests an association between utable to early detection via regular screening, symp-
primary tumor site and mortality. tom awareness, and management. The development
Another possible explanation for the survival dispar- and wide implementation of breast cancer screening
ity between male and female breast cancer patients is recommendations for high-risk male populations might
based on management. A recent NCDB analysis, be- similarly lead to improvements in early detection and
tween 2004 and 2014, revealed a shift in the manage- survival. Currently, breast cancer screening recommen-
ment preferences among male breast cancer patients, dations for male exist for those with a genetic predis-
with more men choosing to receive mastectomy vs. position (including BRCA1 or BRCA2 gene mutations)
breast-conserving surgery (BCS) [20]. One possible ex- and/or a strong family history (1st degree relative with
planation for this trend is that male patients wanted confirmed mutation or breast cancer diagnosis at age
to avoid the radiotherapy that accompanies BCS 40 or younger) [26]. The current clinical efficacy of the
[14,20,21]. But Yadav et al [14] reported a possible cor- implementation of these guidelines remains unclear.
relation between total mastectomy and decreased OS. It is our hope that the information provided from our
Additionally, there was a significant survival benefit analysis of the NCDB is used to shape future medical
for male patients who received adjuvant radiotherapy guidelines and practical recommendations towards the
with BCS, even among stage I male breast cancer cases management of male breast cancer.
[14], which may underscore the potential importance The strengths of this analysis include: 1) the 13-year
of radiotherapy for patients with male breast cancer. duration of data collection, which allowed for the cal-
Future research evaluating gender survival differences culation of median survivorship in males and for the
by management can improve the mortality of male analysis of patient outcomes over time; 2) the large
breast cancer patients. sample size of males, considering the rarity of this dis-
In our analysis, we noted that the 5-year OS was ease; 3) utilizing data collected from a national registry
lowest for the following combination of factors for which allowed for a homogenous sampling of patients
male patients with breast cancer: >70 years of age, >2 across accredited centers in the United States; 4) the
comorbidities, median income <$30,000, and insurance standardized method of data collection within the
with Medicare (compared to other types of insurance). NCDB which maximized the fidelity of the data col-
Unfortunately, the clinical characteristics of those with lected. The limitations of this study include those that
the poorest survival outcomes among their respective are typically encountered when utilizing a registry-
subcategory is typically not reflective of the majority based data set such as limited pathologic information,
of patients recruited into clinical trials. For instance, comorbidity information limited to categorical ranking,
older patients are significantly underrepresented in and lack of detailed treatment categories.
clinical cancer trials [22]; while younger, healthier, and
more highly educated patients are well represented [23]. CONCLUSIONS
Even those over the age of 64 years, with universal
access to Medicare, were found to be less likely to par- This analysis of a large population of male and fe-
ticipate in a clinical trial [24]. This data calls for more male patients, diagnosed with breast cancer between
inclusive participation in clinical trials as a crucial step 2004 and 2016, suggests that male patients with breast
towards addressing the survival gap between male and cancer were older at diagnosis, exhibited more comor-
female breast cancer patients. bidities, presented with a larger proportion of disease
The current paucity of medical resources and male- metastasis, and exhibited more poorly differentiated
specific preventative guidelines might also present an tumor grades. Independent factors found to be associ-
obstacle to closing the mortality gap between genders. ated with poorer OS were: male sex, older age, African
Since the implementation of public health initiatives in American ethnicity, presenting with 2 or more comor-
the 1980s, which promoted the use of screening mam- bidities, having lower income, presenting at later clini-
mograms, breast cancer mortality rates among women cal staging, and having poor tumor differentiation.

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 https://doi.org/10.5534/wjmh.200164

Based on the above data, we propose four recommen- 2011;29:4381-6.

dations: 1) strongly implementing specific breast can- 9. Giordano SH. Breast cancer in men. N Engl J Med
cer screening recommendations for high risk male; 2) 2018;378:2311-20.
considering sex specific differences including primary 10. Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van
tumor site as prognostic criteria with implications on Leeuwen-Stok E, Porter P, et al. Characterization of male
mortality and treatment e.g., inclusion of radiation; 3) breast cancer: results of the EORTC 10085/TBCRC/BIG/
widening the clinical trials eligibility criteria to include NABCG International Male Breast Cancer Program. Ann
historically underrepresented male with breast cancer; Oncol 2018;29:405-17.
and 4) increasing efforts to promote awareness of dis- 11. Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast can-
parities in male vs. female breast cancer. cer: a population-based comparison with female breast can-
cer. J Clin Oncol 2010;28:232-9.
Conflict of Interest 12. Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van
Leeuwen-Stok E, Porter P, et al. Characterization of male
The authors have nothing to disclose. breast cancer: results of the EORTC 10085/TBCRC/BIG/
NABCG International Male Breast Cancer Program. Ann
Author Contribution Oncol 2017;29:405-17.
13. Masci G, Caruso M, Caruso F, Salvini P, Carnaghi C, Gior-
Conceptualization: EBE, ZN. Data curation: ECZ, HL, HL. For- dano L, et al. Clinicopathological and immunohistochemical
mal analysis: ECZ, HL, HL. Supervision: ZN. Writing – original characteristics in male breast cancer: a retrospective case se-
draft: EBE. Writing – review & editing: LE, NB, AS, ZN. ries. Oncologist 2015;20:586-92.
14. Yadav S, Karam D, Bin Riaz I, Xie H, Durani U, Duma N, et
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