103BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
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Breast Cancer: Basic and
Clinical Research
Breast Cancer Characteristics and Survival in a Hispanic Population
of Costa Rica
Nadia Srur-Rivero
1
and Mayra Cartin-Brenes
2
1
Servicio de Oncología Quirúrgica, Unidad de Mama, Hospital San Juan de Dios, Caja Costarricense de Seguro Social,
San Jose, Costa Rica.
2
Escuela de Salud Pública, Universidad de Costa Rica, San Pedro Montes de Oca, Costa Rica.
ABSTRACT
BACKGROUND: Breast cancer characteristics may vary according to the patient’s ethnic group. e goal of this cohort study was to evaluate the charac-
teristics of a group of Costa Rican breast cancer patients and their relationship with survival.
METHODS: Age, stage, tumor grade, immunohistochemistry, lymphovascular invasion, recurrence, and survival data on 199 Hispanic patients with
breast cancer diagnosis, treated between January 2009 and May 2010, were collected from a single institution in San Jose, Costa Rica. e data were sta-
tistically analyzed for signicance.
RESULTS: Median age at diagnosis was 53 years. With a median follow-up of 46.5 months, there was an 88% overall survival rate. irty-seven percent
of the patients (p 0.001) were at stages III and IV during diagnosis. e hormone receptor human epidermal receptor negative phenotype (HR-HER2-)
(p 0.001) was present in 17% of the cases. In a multivariate analysis, local (risk ratio, RR: 7.2; condence interval, CI 95%: 3.8–7.6; p = 0.06) and
distant recurrence (RR: 14.9; CI 95%: 7.7–28.9; p = 0.01) showed the strongest association with the probability of death from the disease. Patients with
HR-HER2- phenotype tumors reported more local recurrences (p = 0.04), a higher tumor grade (p 0.01), and lower overall survival than patients with
other breast cancer phenotypes (p = 0.01).
CONCLUSIONS: Although this study analyzes a modest number of cases, it is an initial insight into factors that may contribute to dierences in breast
cancer outcomes among Hispanic women in Costa Rica. e higher proportion of triple negative tumors, advanced stage, and younger median age at diag-
nosis could contribute to the inferior prognostic described among Hispanic women. ere may be a dierent distribution of tumor subtypes compared to
non-Hispanic white women. Further studies are necessary to conrm such ndings.
KEYWORDS: breast, cancer, Hispanic, Costa Rica, immunohistochemistry
CITATION: Srur-Rivero and Cartin-Brenes. Breast Cancer Characteristics and Survival in a Hispanic Population of Costa Rica. Breast Cancer: Basic and Clinical Research 2014:8
103–108 doi:10.4137/BCBCR.S15854.
RECEIVED: April 10, 2014. RESUBMITTED: June 25, 2014. ACCEPTED FOR PUBLICATION: June 26, 2014.
ACADEMIC EDITOR: Goberdhan Dimri, Editor in Chief
TYPE: Original Research
FUNDING: Statistical analysis funded by Ocina Dra Srur Rivero. Authors disclose no other funding sources.
COMPETING INTERESTS: Authors disclose no potential conicts of interest.
COPYRIGHT: © the authors, publisher and licensee Libertas Academica Limited. This is an open-access article distributed under the terms of the Creative Commons
CC-BY-NC 3.0 License.
CORRESPONDENCE: dra.nadiasrur@gineonco.org
This paper was subject to independent, expert peer review by a minimum of two blind peer reviewers. All editorial decisions were made by the independent academic editor. All authors
have provided signed conrmation of their compliance with ethical and legal obligations including (but not limited to) use of any copyrighted material, compliance with ICMJE authorship
and competing interests disclosure guidelines and, where applicable, compliance with legal and ethical guidelines on human and animal research participants.
Introduction
e population in Costa Rica recently diagnosed with breast
cancer is increasing. According to statistics from Costa Rica’s
National Cancer Registry, the adjusted incidence rate has
increased from 37.66 to 44.09 per 100,000 women in 10 years,
and breast cancer is the leading cause of cancer-related death
in women.
1
Characteristics of the disease appear to be dierent
according to the patient’s ethnic group. Hispanic women seem
to have an increased mortality risk after being diagnosed with
breast cancer, are diagnosed at a later stage,
2–4
report a lower
median age at diagnosis,
5–7
and feature a dierent immuno-
histochemical tumor subtype distribution, compared to non-
Hispanic white women.
6–8
Srur-Rivero and Cartin-Brenes
104 BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
Hormone receptors (HR) are proteins expressed in breast
epithelium and stroma that bind to circulating hormones to
trigger cellular changes. e HRs more extensively studied
in breast cancer are estrogen receptors (ER) and progester-
one receptors (PR).
9
Patients diagnosed with HR+ tumors are
usually older, more responsive to hormone therapy, and tend
to have better disease-free and overall survival.
HER2 is a transmembrane tyrosine kinase receptor that
belongs to the epidermal growth factor group, encoded by
the ERBB2-HER2 oncogene. Its overexpression is associated
with a more aggressive cancer behavior and worse prognosis.
9
erapy with the humanized monoclonal antibody Trastu-
zumab directed to the HER2 receptor has shown an inhibi-
tory eect on tumor growth.
Tumors lacking HR and HER2 expression are associ-
ated with younger age at diagnosis, a more aggressive clinical
course and worse results than other breast cancer subtypes.
e HR-HER2- subtype has been found in higher proportion
in African-American and Hispanic, than in Caucasian and
Asian breast cancer patients.
5,8,10
is cohort study aims to evaluate the traits of a Hispanic
group of breast cancer patients, such as mean age at diagnosis,
stage of disease, tumor grade, immunohistochemistry (IHC),
and their relationship with survival. e purpose is to con-
tribute to improve health programs and adapt them to the
patient’s requirements.
Methodology
We requested the statistics department at San Juan de Dios
Hospital of the Costa Rican Social Security System (Caja
Costarricense del Seguro Social), a reference cancer treatment
center for Costa Rica’s South Central Region, to provide a
list of patients with “breast cancer” diagnosis discharged from
the Hospital from January 2009 to May 2010. e study pro-
cedures were approved by the hospital’s institutional review
board.
e analysis included all Hispanic women newly diag-
nosed with in situ or invasive breast cancer. A group of 199
patients was continuously selected from the list by the medi-
cal records department and clinical-pathological data were
collected for each patient. e data analyzed in each medi-
cal record, if any, were patient’s age in years, ethnicity, cancer
stage, subsequent hospitalizations, operative note, pathology
report, and follow-up visits to the Hospital until June 1, 2013.
Information on stage and lymph node status was collected
according to the American Joint Committee on Cancer’s
(AJCC, 7th edition) staging criteria. e histopathological
type was classied as ductal, lobular, both, or other. Histo-
logic grading was classied according to the modied Bloom
and Richardson method by Elston and Ellis (Nottingham’s
grading system). Lymph vessel invasion was assessed using
hematoxylin–eosin stained glass slides. Vascular channels
lined by thin endothelial cells, especially close to the small
arteries and veins, were considered as lymph vessels, and
tumor emboli were oating in the lumen in lymph vessel
invasion-positive cases.
Immunohistochemical subtypes such as ER, PR, and
HER2 status were determined by IHC. Antigen retrieval was
performed in a decloaking steam chamber. Manual antibody
incubation, DAKO “in vision” detection system, DAB Chro-
mogen System, and bluish Gill H&E staining using lithium
carbonate were used. For HR receptor staining, primary
antibodies were applied at a 1:30 dilution for 1 hour. After
30-minute incubation with a secondary antibody, DAKO
detection solution was applied. e last step was the addition
of a substrate–chromogen solution. e cuto for receptor
positivity was 1%.
For HER2 staining, primary HER2 antibodies were
applied for 30 minutes. After 30-minute incubation with
a secondary antibody, a substrate–chromogen solution was
added. It was scored on a qualitative scale based on staining
intensity: 0 and 1+ were negative; 3+ was considered posi-
tive; and 2+ was considered borderline, and sent to an exter-
nal laboratory for uorescence in situ hybridization (FISH)
evaluation. FISH was scored on a quantitative scale: less than
2 copies of the HER2 gene was negative, and 2 or more copies
was HER2-positive.
Follow-up visits until June 1, 2013 were analyzed for dis-
tal or local recurrence. Patients with initial metastatic disease
were separated from patients who experienced distant recur-
rence a period of time after initial diagnosis. e survival sta-
tus and date of death were conrmed at the Civil Registry of
Costa Rica on a case-by-case basis. Survival time was dened
in days from the time of diagnosis at the hospital to the date
of death, or survival conrmation on June 1, 2013. Seven
variables were selected and identied by their signicance for
mortality statistical analysis.
Statistical Analysis
Sample size. In 2009 and 2010, there were a total of
957 and 997 newly diagnosed breast cancer cases in Costa
Rica. e sample size was calculated based on 87% expected
survival, which in statistical terms is a proportion, for
which the formula N = Z
2
× P × (1 – P)/D
2
was used, where
Z= CI chosen (if α = 95%, Z = 1.96); P = expected ratio, 0.87;
D = maximum error, 0.05; and n = sample size, 173. Although
the recommended sample size is 173 cases, information for
more cases was collected due to the probability of nding
records with incomplete information. Since the information
was obtained retrospectively from medical records, selection
bias was avoided because the sample was selected randomly.
For descriptive purposes, continuous variables were sum-
marized as arithmetic means with standard deviations and
medians with ranges, and categorical variables were summa-
rized as relative frequencies, ratios, and 95% CIs. Inferential
comparisons were performed using the Student’s t-test or the
Breast cancer characteristics in Costa Rica
105BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
Mann–Whitney U test according to distribution (normal or
not normal) determined by the Kolmogorov–Smirnov test.
Pearson chi-square tests and relative risk ratios (RRs) were
used to compare the clinical and pathological variables. For the
multivariate analysis, the variables included were those bearing
clinical signicance and those that were signicant or nearly
statistically signicant (p 0.05) in the univariate analysis.
All variables were dichotomized for survival analysis.
Adjustment of potential confounders was carried out with
Cox proportional hazards regression analysis. All tests were
two-sided, and signicance was set at p 0.05. SPSS soft-
ware (version 20.0; SPSS, Chicago, Il) was used for data anal-
ysis purposes.
Dierences between breast cancer subtypes with regards
to clinical-pathological characteristics were examined using
analysis of variance, c
2
tests, or Fisher’s exact test. e log-
rank test was used to compare mean survival across IHC
subtypes. StatView statistical software (version 3.0; Abacus,
Baltimore, MD) was used to manage and analyze data. Statis-
tical dierences were considered signicant at p 0.05.
Results
Clinical-pathological and non-cancer specic survival data on
199 Hispanic patients with breast cancer diagnosis were col-
lected from a single institution in San Jose, Costa Rica.
Table 1 displays the population’s general characteristics.
Median age at breast cancer diagnosis was 53 years. e his-
topathological type was 80% ductal carcinoma. Stage was dis-
tributed as follows: Stage 0, 3%; stages I and II, 59.3%; and
stages III and IV, 37.1%. Survival for a median follow-up of
46.5 months was 88%. e immunohistochemical subtypes
were HR+HER2-, 62.3%; HR+HER2+, 9%; HR-HER2+,
9.5%; and HR-HER2-, 17.1%. e proportion of HR-
and/or HER2+ tumors was higher for patients under 50 years
than for older patients, this relation is not statistically signi-
cant (p = 0.32). ere were 7 (3.5%) local and 11 (5.52%) dis-
tant recurrences.
Using the univariate analysis, there were dierences in
age (p = 0.003), stage (p 0.001), immunohistochemichal
subtype (p = 0.02), lymphovascular invasion (p = 0.015), local
recurrence (p 0.001), distant recurrence (p 0.001), and
survival. No statistically signicant dierence was found for
histologic grade (p = 0.33) and survival.
Dichotomized variables and their analysis are included in
Table 2. In the univariate analysis, age 50 years (p 0.001,
RR: 4.1), stages III and IV (p 0.001, RR: 5.8), presence
of lymphovascular invasion (p 0.02), HR-HER2- IHC
(p 0.001, RR: 2.7), local recurrence (p 0.001, RR: 7.2),
and distant recurrence (p 0.001, RR: 14.9) were statisti-
cally signicant dierences in patients who died after diagno-
sis. Grade III tumor (p = 0.18, RR: 1.8) was not signicantly
associated with survival. In the multivariate analysis, local
(p = 0.06) and systemic recurrence (p = 0.01) showed the
strongest association with the probability of dying from the
disease.
Table 3 shows the characteristics of 195 patients accord-
ing to the immunohistochemical subtype. Dierences in
histological grade (p 0.01) were observed: grade III was
less frequent in the HR+HER2- subtype (21.8%) and more
frequent in the HR-HER2- subtype (64.7%). Local recur-
rence showed an uneven distribution in the study groups
(p = 0.04), the event being most frequent in HR-HER2-
patients (11.8%). With a median follow-up of 45.6 months,
breast cancer subtypes signicantly diered in survival rate
(p = 0.01): HR+HER2-, 91.9%; HR+HER2+, 94.4%; HR-
HER2+, 89.5%; and HR-HER2-, 73.5%.
Patients with HR- and/or HER2+ overexpression tumors
were more likely to present with an advanced stage than
patients with HR+HER2- tumors; however, this was not sta-
tistically signicant (p = 0.18). No signicant dierences were
found in age (p = 0.44), lymphovascular invasion (p = 0.86),
and distant recurrence (p = 0.42) between subgroups.
Discussion
e median age at diagnosis of this group of patients was
53 years. Dierent to the mean age at breast cancer diagnosis
of 61–63 years among Australian and European women;
11
a
younger median age at cancer diagnosis has been described
for Hispanic women.
4–8,12
In some studies, the median age is
10 years younger than the average age reported in the United
States, and there is a higher proportion of non-Hispanic whites
(57%) diagnosed with breast cancer younger than 60-years
old, when compared to their white counterparts (47%).
2–4
e distribution of breast cancer subtypes among young
patients has been found to be dierent from that observed in
older women, and has further variations with race/ethnicity.
Young women are also more likely to be diagnosed with stages
III/IV disease and high-grade tumors than older women.
13
Hispanics are described as the ethnic group with the highest
percentage of women under 41 years diagnosed with breast
cancer.
8
irty-seven percent of the patients in the group had
stages III and IV cancer at diagnosis. is is much higher than
the number described in other studies for Central and South
American women with stages III and IV cancer at diagnosis
(14.3%).
2
Social and cultural barriers, like “fear to be left by
her partner, poor awareness of the population and primary
health providers, as well as decient mammographic screen-
ing programs,” could lead to an advanced stage at diagnosis.
4
Hispanic women have been found to have a 1.7- to 2.5-fold
elevation in the risk of stages III and IV tumors, compared
to non-Hispanic whites.
2–6,14
Warner et al
3
found Hispanic
and other minority women were more likely to show up with
cancer symptoms versus a problem detected through screen-
ing mammography, and experienced longer times from initial
signs of cancer to nal diagnosis.
Srur-Rivero and Cartin-Brenes
106 BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
Table 1. General characteristics of patients with breast cancer in
Costa Rica.
NO. OF PATIENTS, (%) P VALUE*
Age, years-old
50 years
74 (37.2)
50–70 years 103 (51.8) .03
70 years
22 (11.1)
AJCC stage
0 6 (3)
I 35 (17.6)
IA 31 (15.6)
IB 4 (2)
II 83 (41.7)
IIA 50 (25.1)
IIB 33 (16.6)
.001
III 67 (33.6)
IIIA 38 (19.1)
IIIB 15 (7.5)
IIIC 14 (7)
IV 7 (3.5)
Missing 1 (0.05)
Immunohistochemical (IHC) subtype
HR+/HER2-
124 (62.3)
50 years
41 (20.6)
50 years
83 (41.7)
HR+/HER2+
18 (9)
50 years
8 (4.02)
50 years
10 (5.02)
HR-/HER2+
19 (9.5) .02 .32*
50 years
10 (5.02)
50 years
9 (4.52)
HR-/HER2-
34 (17.1)
50 years
14 (7.03)
50 years
20 (10.05)
Missing 4 (2.01)
Histologic grade
Grade I 27 (13.6)
Grade II 74 (37.2) .33
Grade III 62 (31.1)
Missing 36 (18.1)
Lymphovascular
Invasion present 34 (17.08)
Absent 66 (33.16) .015
Missing 99 (49.74)
Local recurrence
Present 7 (3.58)
.001
Absent 192 (98.46)
Distal
Recurrence 11 (5.53)
Present 182 (91.46)
.001
Absent 6 (3.02)
Stage IV
Notes: *Univariate analysis. **IHC subtype and age.
e group of patients diagnosed with stage I disease was
small (17.6%). In previous publications, only a small percent-
age of Hispanic women are diagnosed with stage I breast
cancer,
2–6,14
Walters et al reported that stage I at diagnosis
ranged from 30% to 45%, and stages III and IV from 8% to
22%, depending on the screening program implemented by the
country, in a European, Canadian, and Australian population
study.
11
Sassi et al described that Hispanic women who devel-
oped breast cancer had somewhat lower probability of early
stage diagnosis than non-Hispanic white women, but with
more steeply increasing screening rates, there was a similar
increase in the number of cases diagnosed at an early stage.
15
Rodriguez-Cuevas et al described results of a rst mammog-
raphy screening program in Mexico. Even though it was a
case study of 208 patients, one-third of diagnosis were stage
0 or I, 42%, stage II and 26.7%, stage III. ese results were
dierent from other published data of Mexican breast cancer
series, in which 25–40% were stages I and II and 57% were
stages III and IV.
5
In our study, the percentage for the HR-HER2-
phenotype is higher (17.1%) than in non-Hispanic whites
(11.7–12.5%).
7,8
is proportion (17.2–17.3%) has been
reported for Hispanics in previous studies,
16,10
which is higher
than the one reported for Japanese patients (8%),
17
but lower
than for African-Americans (24.6–27.9%).
8,10
A higher pro-
portion of HR- HER2- (23%) has also been described by
Lara-Medina et al in Hispanic patients.
6
Patients with HR-HER2- phenotype tumors expe-
rienced more local recurrences, had higher tumor grades,
and lower overall survival than patients with other breast
cancer phenotypes. Hispanics have been found more likely
to present high-grade tumors than non-Hispanic whites.
7
HR-HER2- tumors exhibit in average a high-grade tumor:
over 80% of HR-HER2- tumors have high histologic grade,
compared to less than 20% of the HR+HER2- tumors.
8,18
Local recurrence has been described as three times higher
in patients with the HR-HER2- phenotype than with the
HR+HER2- phenotype.
18
ree-year survival for HR-HER2- patients was lower
than for patients with other inmunohistochemical subtypes
(73.5%). In California studies, survival among women with
HR-HER2- breast cancer was lower: they reported a 76–77%
5-year survival rate, compared to 93–96% 5-year survival rate
for women with other types of breast cancer.
10,19,20
In Japanese
women, there was also a lower overall survival (86.2%) for
basal-like cancer than for the luminal A phenotype (96.9%).
17
With a median follow-up of 46.5 months, there was an
88% survival rate for patients in this group. ere was a 3-year
overall survival rate of 91% to 94% in other two European
countries, Canada, and Australia, compared to 87% and 89%
in UK and Denmark, related to screening implementation and
dierences in treatment.
11
Hispanics have been described to
have a 1.3- to 2-fold increase in mortality risk compared to
non-Hispanic whites.
2,21
Breast cancer characteristics in Costa Rica
107BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
Table 2. Dichotomized clinico pathologic characteristics of patients with breast cancer in Costa Rica.
CHARACTERISTIC NO. OF PATIENTS, (%) UNIVARIATE ANALYSIS MULTIVARIATE LOGISTIC
REGRESSION ANALYSIS P
ALIVE DEAD P RR (95% CI)
Age
50 years
71 95.9% 3 4.1%
50 years
104 86.0% 17 14.0%
.01
4.1 (1.2–13.4) .95
AJCC stage
I and II 113 95.8% 5 4.2%
III and IV 55 75.3% 18 24.7%
.001
5.8 (2.25–414.9) .59
Histologic grade
1 and 2 93 92.1% 8 7.9 %
3 53 85.5% 9 14.5% .18 1.8 ( 0.74–4.5) NA
Lymphovascular invasion
Absent 34 100% 0 0%
Present 52 78.8% 14 21.2% .015 NA .94
Distant recurrence
No 172 94.5% 10 5.5%
Yes 2 18.2% 9 81.8%
.001
14.9 (7.7–28.9) .01
Local recurrence
No 173 90.1% 19 9.9%
Yes 2 28.6% 5 71.4%
.001
7.2 (3.8–13.6) .06
Immunohistochemical subtype
HR+HER2-, HR+HER2+, and HR-HER2+
148 91.9% 13 8.1%
HR-HER2-
25 73.5% 9 26.5%
.001
2.7 (1.2–5.8) .93
Abbreviations: RR, relative risk; CI, condence interval.
Table 3. Prevalence of immunohistochemical subtypes and clinico-pathologic characteristics of patients in Costa Rica.
ALL CASES
HR+HER2- HR+HER2+ HR-HER2+ HR-HER2-
P VALUE*
Number of cases 195 124 18 19 34
Age, median (range), years-old 53 (24–88) 54 (24–86) 50.5 (29–71) 49 (26–72) 52 (27–88) .44
AJCC stage
I and II 114 58.5% 81 65.9% 8 53.3% 7 41.2% 18 54.5% .18
III and IV 74 37.9% 42 34.1% 7 46.7% 10 58.8% 15 45.5%
0 6 3.1%
Missing 1 0.5%
Histologic grade
I and II 99 50.8% 79 63.7% 9 50.0% 8 42.1% 3 8.8%
.01
III 61 31.3% 27 21.8% 5 27. 8% 7 36.8% 22 64.7%
Missing 35 17. 9% 18 14.5% 4 22.2% 4 21.1% 9 26.5%
Lymphovascular invasion
Present 34 17.4% 24 19.4% 3 16.7% 2 10.5% 5 14.7% .86
Absent 66 33.8% 43 34.7% 5 2 7. 8% 7 36.8% 11 32.4%
Missing 95 4.7% 57 46.0% 10 55.6% 10 52.6% 18 52.9%
Local recurrence
Present 7 3.6% 3 2.4% 0 0% 0 0% 4 11.8% .04
Absent 188 96.4% 121 97. 6% 18 100.0% 19 100.0% 30 88.2%
Distant recurrence
Present 11 5.6% 6 4.9% 0 0% 2 10.5% 3 9.7% .42
Absent 178 91.3% 116 95.1% 17 100% 17 89.5% 28 90.3%
Initial stage IV 6 3.1%
Follow-up, median (range), months 45.6 (2–55.4)
Overall survival 88.7% 91.9% 94.4% 89.5% 73.5% .01**
Notes: *Compares four subtypes using Fisher’s exact text. **Log rank test.
Srur-Rivero and Cartin-Brenes
108 BREAST CANCER: BASIC AND CLINICAL RESEARCH 2014:8
Hines et al
7
found tumor single marker staining for
HER2+ was 31.9% in Hispanics, compared to 14.3% in non-
Hispanic whites. In our study, 18.5% of the tumors displayed
single marker staining for HER2+, or were FISH+. e
slightly higher survival in this study for the HR+HER2+ sub-
type compared to the HR+HER2- may be explained in part
by public access to treatment and systemic therapies, as well as
sample size and short follow-up period.
Information from patient records was not found for tumor
grade in 18.1% of the cases and for lymphatic invasion in 50%
of the cases. No standardized synoptic report for breast can-
cer was used by pathologists at the time; therefore, informa-
tion was omitted in some pathology reports. Future changes
in reporting are expected with the recent implementation of
the standardized synoptic report for breast pathology, and the
assignment of a specialized group of pathologists to work on
breast diseases.
e study's weakness is that the patient cohort is from a
single institution, which is a reference cancer treatment center
for Costa Rica’s South Central Region; hence, the data may
not reect the true epidemiology of the entire Hispanic popu-
lation in Costa Rica.
is is the rst published study of breast cancer clinical-
pathological characteristics and survival of Costa Rican breast
cancer patients, according to Medline search terms: breast
cancer, Costa Rica.
Conclusions
ese ndings may provide an initial insight to factors that con-
tribute to dierences in breast cancer outcomes among Hispanic
women in Costa Rica. e higher proportion of triple negative
tumors, advanced stage, and younger median age at diagnosis
could lead to a worse cancer prognosis in this group.
e higher proportion of stages III and IV tumors
at diagnosis demands a review of the region’s breast cancer
screening program. It is important to make emphasis on breast
cancer awareness programs for the population and primary
care physicians, and to investigate social and cultural barriers
that make earlier cancer detection a dicult task.
Since patients are diagnosed at a younger age, it is desir-
able to organize programs for fertility preservation and genetic
testing, among others, to improve patient care.
Acknowledgments
We thank Allan Ramos MD for providing data collection
support, and Yetty Vargas MD, Adonay Jaen and Jason, San
Juan de Dios IHC pathology technicians for their help with
the IHC specications for our study. We also thank Angela
Ulloa for her help editing the manuscript.
Author Contributions
Conceived and designed the experiments: NSR. Analyzed the
data: NSR, MCB. Wrote the rst draft of the manuscript: NSR.
Contributed to the writing of the manuscript: NSR, MCB.
Agree with manuscript results and conclusions: NSR, MCB.
Jointly developed the structure and arguments for the paper:
NSR, MCB. Made critical revisions and approved nal ver-
sion: NSR, MCB. All authors reviewed and approved of the
nal manuscript.
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