Comparative study of breast cancer in Mexican and Mexican-American women

doi:10.4236/health.2010.29153

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Vol.2, No.9, 1040-1048 (2010) Health

doi:10.4236/health.2010.29153

Comparative study of breast cancer in Mexican and

Mexican-American women

María Elena Martínez1*, Luis Enrique Gutiérrez-Millan2, Melissa Bondy3,

Adrian Daneri-Navarro4, María Mercedes Meza-Montenegro5, Ivan Anduro-Corona2,

Ma Isabel Aramburo-Rubio6, Luz María Adriana Balderas-Peña7,

José Adelfo Barragan-Ruiz7, Abenaa Brewster3, Graciela Caire-Juvera8,

Juan Manuel Castro-Cervantes7, Mario Alberto Chávez Zamudio9, Giovanna Cruz1,

Alicia Del Toro-Arreola4, Mary E. Edgerton3, María Rosa Flores-Marquez7,

Ramon Antonio Franco-Topete10, Helga Garcia5, Susan Andrea Gutierrez-Rubio4,

Karin Hahn3, Luz Margarita Jimenez-Perez11, Ian K. Komenaka12, Zoila Arelí López Bujanda2,

Dihui Lu13, Gilberto Morgan-Villela7, James L. Murray3, Jesse N. Nodora14,

Antonio Oceguera-Villanueva15, Miguel Angel Ortiz Martínez13, Laura Pérez Michel13,

Antonio Quintero-Ramos9, Aysegul Sahin3, Jeong Yun Shim3, Maureen Stewart3,

Gonzalo Vazquez-Camacho7, Betsy Wertheim1, Rachel Zenuk1, Patricia Thompson1

1Arizona Cancer Center and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, USA;

*Corresponding Author: emartinez@azcc.arizona.edu

2Departamento de Investigaciones Científicas y Tecnológicas, Universidad de Sonora, Hermosillo, México

3University of Texas M.D. Anderson Cancer Center, Houston, USA

4Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México

5Instituto Tecnológico de Sonora, Ciudad Obregón, México

6Instituto Mexicano del Seguro Social, Hermosillo, México

7Instituto Mexicano del Seguro Social, CMNO, Guadalajara, Jalisco

8Centro de Investigación en Alimentación y Desarrollo, Hermosillo, México

9Instituto Mexicano del Seguro Social, Ciudad Obregón, México

10OPD Hospital Civil de Guadalajara, Guadalajara, México

11Departamento de Salud Pública, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México

12Maricopa Medical Center, Department of Surgery, Phoenix, USA

13University of North Carolina, Lineberger Cancer Center, Chapel Hill, USA

14Arizona Cancer Center and Department of Family and Community Medicine, University of Arizona, Tucson, USA

15Instituto Jalisciense de Cancerología, Guadalajara, México

Received 25 March 2010; revised 5 May 2010; accepted 7 May 2010.

ABSTRACT

Breast cancer is the number one cause of can-

cer deaths among Hispanic women in the United

States, and in Mexico, it recently became the

primary cause of cancer deaths. This malign-

nancy represents a poorly understood and un-

derstudied disease in Hispanic women. The

ELLA Binational Breast Cancer Study was es-

tablished in 2006 as a multi-center study to as-

sess patterns of breast tumor markers, clinical

characteristics, and their risk factors in women

of Mexican descent. We describe the design and

implementation of the ELLA Study and provide a

risk factor comparison between women in the

U.S. and those in Mexico based on a sample of

765 patients (364 in the U.S. and 401 in Mexico).

Compared to women in Mexico, U.S. women had

significantly (p < 0.05) lower parity (3.2 vs. 3.9

mean live births) and breastfeeding rates (57.5%

vs. 80.5%), higher use of oral contraceptives

(60.7% vs. 50.1%) and hormone replacement

therapy (23.3% vs. 7.6%), and higher family

history of breast cancer (15.7% vs. 9.0%). Re-

sults show that differences in breast cancer risk

factor patterns exist between Mexico and U.S.

women. We provide lessons learned from the

conduct of our study. Binational studies are an

important step in understanding disease pat-

terns and etiology for women in both countries.

M. E. Martínez et al. / HEALTH 2 (2010) 1040-1048

1041

Keywords: Binational Study; Breast Cancer;

Hispanics; Mexico; United States

1. INTRODUCTION

Rates of breast cancer in more developed nations have in

the past exceeded those in lower-income countries by a

factor of five or more [1]. In Mexico, the breast cancer

mortality rate has increased by 84% over the last two

decades [2,3] and it is now the most commonly diagnosed

cancer among women in Mexico [3]. In the United States

(U.S.), age-adjusted breast cancer incidence differs sig-

nificantly among racial/ethnic groups; rates are higher

among non-Hispanic whites (NHWs) and lower among

racial/ethnic minorities, including Hispanics [4]. Despite

their lower breast cancer incidence rates, Hispanic women

are 22% more likely to die of this disease [5]. Published

data [6-10], including our own studies in Arizona [11],

indicate that Hispanic women present with breast cancer

at an earlier age and with larger, more advanced stage

disease of higher grade, a profile similar to that observed

for African-American women. Relative to other racial/

ethnic groups, few epidemiological studies that focus on

breast cancer in Hispanic women have been conducted

to date. Published reports have provided data on the role

of reproductive factors [12,13], body size and obesity

[14], physical activity [15,16], contraceptive use [12,17],

diet [18], family history [13], and migration history [12,

19], in relation to breast cancer risk in Hispanic women

in the U.S.

It is now generally accepted that breast tumors exhibit

heterogeneity derived from intrinsic molecular differ-

ences that influence their natural history and response to

treatment [20]. A number of studies have shown that

steroid hormone dependent tumors differ with respect to

their biology and their risk factors [21] and that these

differences are clinically relevant in terms of treatment

selection, response, and patient prognosis [22-24]. In

spite of the importance of characterization of breast

cancer disease subtypes, no published data exist on the

prevalence of the tumor subtypes, such as luminal and

basal-like breast tumors in Hispanic women in the U.S.

Results of the few population-based studies published to

date [25-27], including our own [11], suggest that His-

panic women with breast cancer are more likely to be

diagnosed with hormone receptor negative tumors and

those that do not express human epidermal growth factor

receptor 2 (HER2), compared to NHWs [28,29].

Reasons for breast cancer disparities in Hispanic women

likely result from a combination of factors including

poor access to health care, less use of mammography

screening, genetic susceptibility, and environmental or

cultural factors. While there is increasing scrutiny of the

validity and theoretical basis of acculturation measures

[30-32], adequate and nuanced measurement of accultu-

ration could allow for the identification of variables

linked to risk-enhancing or protective behaviors associa-

ted with breast cancer and its subtypes.

The ELLA Binational Breast Cancer Study (hereafter

referred to as the ELLA Study) was established to

compare risk factor patterns, disease phenotypes, and

clinical characteristics between the U.S. and Mexico

populations. We hypothesized that the distribution of

breast tumor subsets differs between women in Mexico

and Mexican-American women residing in the U.S. and

that these differences are related to reproductive and

lifestyle factor profiles indicative of U.S. lifestyle and

cultural influences. Here we describe the design and

implementation of this binational study and provide a

comparison of risk factor characteristics between the two

countries.

2. METHODS

2.1. Study Design and Recruitment

The ELLA Study was initiated in 2006 as a pilot effort

with the formation of a binational investigative team,

comprising three sites in Mexico (Universidad de Gua-

dalajara in Guadalajara, Jalisco; Universidad de Sonora

in Hermosillo, Sonora; and Instituto Tecnológico de

Sonora in Ciudad Obregón, Sonora) and two sites in the

U.S. (Arizona Cancer Center, in Tucson, Arizona, which

included recruitment sites throughout the state; and at

the University of Texas M.D. Anderson Cancer Center in

Houston, Texas, which included two additional recruit-

ment sites) (See Table 1). An essential component of the

ELLA study was the partnership with clinicians and

pathologists from health care settings serving the study

participants both in Mexico and the U.S. Health care

providers included those from Mexico’s nationalized

health care system: the Instituto Mexicano del Seguro

Social (IMSS) in all three sites and the Hospital Civil

and Instituto Jaliscience de Cancerología in Guadalajara.

The study was approved by the respective Institutional

Review Boards, including the IMSS. Written informed

consent was obtained for all participants.

Participants were eligible if they were diagnosed

within 24 months of recruitment with invasive breast

cancer and were 18 years of age or older. In the U.S., par-

ticipants were self-identified as being of Mexican descent.

Women with carcinoma in situ and those with recurrent

disease were ineligible. A clinic-based approach was the

dominant strategy used for recruitment in the study,

although the number of recruitment sites and their tactics

M. E. Martínez et al. / HEALTH 2 (2010) 1041-1048

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of identifying patients differed by region (see Table 1).

2.2. Data Collection

Participation involved in-person (93%) or telephone ad-

ministration (7%) of a risk factor questionnaire. Three

comparable questionnaires were created: English and

Spanish versions for the U.S. and a separate instrument

for Mexico. No differences existed between the two U.S.

versions and only minor differences between the U.S.

and Mexico questionnaires (see Table 2).

All study personnel were jointly trained prior to the

initiation of recruitment and continue to receive training

as needed. The instrument takes a median of 45.0 min-

utes to administer (59.0 minutes for Mexico and 43.2

minutes for the U.S.).

As part of data collection, we abstracted the medical

records for clinical and histopathological factors, includ-

ing predictive and prognostic factors. It is important to

note that ER, PR, and HER2 are not uniformly con-

ducted in all IMSS institutions in Mexico; marker status

is not conducted at all in the Hospital Civil or the Insti-

tuto Jaliscience de Cancerología. The Avon Foundation,

one of the study’s sponsors, provided additional funding

for the breast cancer patients to have consistent tumor

marker information that is important for their treatment

course.

Figure 1 presents the operational structure of the

ELLA Study. The organizational structure includes the

five recruitment sites, the research core elements, and

the Steering and Advisory Committees. Recruitment,

data collection, tissue collection, and DNA extraction are

conducted at each site.

2.3. Biological Samples

An essential component of the ELLA Study was the

routine collection of formalin fixed paraffin embedded

(FFPE) breast cancer tissue including biopsy sample for

patients receiving neoadjuvant therapy. FFPE tissue

samples were sent to M.D. Anderson Cancer Center for

the construction of tissue microarrays (TMAs) (Figure

1). The markers being evaluated in the TMAs were

selected to characterize basal and luminal subtypes (ER,

PR, and HER2, Ki67, epidermal growth factor receptor

(EGFR) and basal cytokeratins [CK5 or 6, CK14 and

CK17]) for subset delineation by immunohistochemistry

as described by Nielsen et al. [33]. Prior to initiation of

the ELLA recruitment, special trainings were conducted

at Ventana Medical Systems (Tucson, Arizona) that in-

cluded all Mexico pathologists involved in the study. To

assure uniformity of tumor marker measures of diagno-

stic value across community and international laborato-

ries, ER, PR, HER2, and Ki67 analyses were repeated on

all tumor samples at Ventana Medical Systems with auto-

mation and intra- and inter-batch control. We do not

present clinical characteristics or marker data due to their

premature nature as data derived from Mexico will need

to undergo quality control verification.

Figure 1 also shows the establishment of a deoxyribo-

nucleic acid (DNA) repository with the collection of

blood or saliva on all participants. DNA was extracted at

each recruitment site from saliva according to manufac-

turer instruction for the Oragene saliva kit (DNA Genotek©,

Ontario Canada) or from blood using the QIAmp Mini

Kit (Qiagen©, Valencia CA). A single DNA aliquot was

then sent to the Arizona Cancer Center for study banking

with each site retaining the remainder of their study

DNA.

2.4. Data Management and Tissue Tracking

Data management supporting the risk factor question-

naire and medical record abstraction for the ELLA Study

was centralized at the Arizona Cancer Center. We de-

veloped web-based databases built with two well-establi-

shed open-source software systems, providing the capac-

ity to allow access from anywhere via the Internet. Da-

tabase applications were built around the individual needs

Table 1. Recruitment sites in the ELLA study, March 1, 2007 to June 1, 2009.

Region Recruitment Sites

Arizona (United States)

Arizona Cancer Center (Tucson); St. Elizabeth of Hungary Clinic (Tucson); University Physician’s

Healthcare Kino Hospital (Tucson); El Rio Community Health Center (Tucson); Arizona Oncology

(Tucson); Maricopa Integrated Health System (Phoenix); Mountain Park Community Health Center

(Phoenix); Dr. Edward Donahue (Phoenix); Arizona Oncology (Phoenix); Mariposa Community Health

Center (Nogales); Regional Center for Border Health (Yuma).

Houston, Texas (United States) M.D. Anderson Cancer Center; Lyndon B. Johnson Hospital; The Rose Diagnostic Clinic.

Guadalajara, Jalisco (Mexico) Instituto Mexicano del Seguro Social; OPD Hospital Civil de Guadalajara; Instituto Jaliscience de

Cancerología.

Ciudad Obregon, Sonora (Mexico) Instituto Mexicano del Seguro Social.

Hermosillo, Sonora (Mexico) Instituto Mexicano del Seguro Social.

M. E. Martínez et al. / HEALTH 2 (2010) 1040-1048

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Table 2. Characteristics of the risk factor questionnaire and the medical record abstraction in the ELLA study.

Characteristic Details

Sociodemographics Date and place of birth, residence history, age at migration to the U.S. (U.S. only), education, marital status,

religious preference, income (Mexico only), parents’ place of birth, poverty index (Mexico only).

Occupational history Longest paid job held for one year or longer; farm work.

Pesticide exposure Exposure at home, residence in or near agricultural community.

Acculturation/

Westernization

Language use, media language exposure (U.S. only). Westernization questionnaire developed for Mexican pa-

tients.

Tobacco Exposure Cigarette use status (never, past, current), dose, and duration. Second-hand smoke exposure history.

Alcohol History Alcohol use, type, dose and duration.

Menstrual history Age at menarche, menstrual cycle regularity. Age at menopause and type.

Pregnancy history Age at pregnancy, number of full term pregnancies, type of birth, breast feeding, weight gain.

Breast health history History of breast self exam, clinical breast exam, mammography, biopsies.

Method of breast cancer detection, symptoms, delay in care, reason(s) for delay.

Medical history History of diabetes, hypertension, heart disease, endometriosis, autoimmune disease(s), polycystic ovaries, gall-

bladder disease, radiation to the chest.

Medication use Use of aspirin/nonsteroidal anti-inflammatory drugs and oral corticosteroids, dose, and duration.

Birth control and hormone

use Type of birth control and history of use. HRT use, type, and duration.

Family history of cancer First and second degree family members, type of cancer, and age at diagnosis of affected family member.

Physical activity Time spent in occupational, housework, and recreational activities and activity type. Sedentary behavior (time

spent sitting and sleeping). Activity level at various ages during lifetime.

Anthropometrics Height, weight, and weight history. Waist and hip measurement.

Medical Record abstraction Site of recruitment. Age at diagnosis. Stage, histology, tumor markers (ER, PR, HER2).

Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HRT, hormone replacement therapy; PR, progesterone receptor; U.S.,

United States

of the study and tailored to meet its specific tasks. With

Secured Socket Layer (SSL) certificate, the password

protected online database application was free of inter-

cept by others during data transmission from each study

site to the database server. We developed a tissue track-

ing database in Oracle (Oracle, Redwood Shores CA),

a relational database using caTissue Version 1.0 structure

with extensions to track tissue transfer across the ELLA

consortium (Figure 1). All bodily fluids and FFPE tissue

samples were inventoried in the ELLA Station and the

data are secure at the M.D. Anderson Cancer Center. The

database can be accessed via a browser-based front end

using Java Server Faces

3. RESULTS

Data presented are based on 765 study participants re-

cruited as of June 1, 2009 (364 in the U.S. and 401 in

Mexico). The majority (78.9%) of participants were in-

terviewed within one year of diagnosis. Response rates

were extremely high, ranging from 95 to 99%. Table 3

presents selected risk factor characteristics for the total

population as well as by country.

Women in the U.S. were significantly younger than

those in Mexico. Fifty-nine percent of the U.S. patients

were born in Mexico and the majority has lived in the

U.S. for over ten years. We recruited roughly equal pro-

portions of English and Spanish speakers in the U.S.

Women in Mexico had a significantly higher number of

live births and rates of breastfeeding. The proportion of

post-menopausal women was significantly higher in Me-

xico than the U.S. Use of oral contraceptives and hor-

mone replacement therapy were significantly higher in

the U.S. than Mexico, but use of hormone therapy was

low overall (14%). Women in Mexico were less likely to

have had prior mammography. Although obesity rates

were equally high in both countries, women in Mexico

reported a lower BMI at age 30 compared to those in the

U.S. Current cigarette smoking was low in both coun-

tries, whereas alcohol consumption was significantly

higher in the U.S. than in Mexico.

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Advisory Committee

Steering Committee

Principal Investigators

US SITES

MDACC University of Arizona

MEXICO SITES

Universidad of SonoraUniversidad de GuadalajaraInstituto Tecnológico de Sonora

Tumor Tissue Collection

•Collection at each site

•TMA construction at MDACC

Sample Collection

•Blood or Saliva

•DNA Extraction at each site

IT/Data Management

•Questionnaire and Medical Record Data

•Web-based database housed at Arizona

Tumor Tissue DNA

Extraction and

Genotyping

Blood/Saliva DNA GenotypingStatistics

Figure 1. ELLA binational breast cancer study organizational structure. The organizational structure

includes the five recruitment sites, the research core elements, and the Steering and Advisory Com-

mittees. Recruitment, data collection, tissue collection, and DNA extraction are conducted at each

site. Tracking of participants, Risk Factor Questionnaire (RFQ), Medical Record Abstraction (MRA),

and biological samples (deoxyribonucleic acid [DNA] and Tissue Microarray [TMA] repositories)

are maintained in separate but integrated databases. Databases can be accessed via browser-based

front end using Secured Socket Layer certificate.

4. DISCUSSION

In 2006, there were 44.3 million Hispanics (14.8 percent

of total) in the U.S., with those of Mexican descent

comprising 64 percent of the total. It is projected that the

Hispanic population will grow to 102.6 million (24.4

percent of total) by 2050 [34], making it the fastest

growing racial/ethnic minority group in the U.S. In addi-

tion, foreign born individuals from Mexico comprise the

largest immigrant group in the U.S. In spite of the con-

tinued growth of the Hispanic population in the U.S.

(44.3 million in 2006) [34] and the fact that breast can-

cer represents the number one cause of cancer deaths in

Hispanic women [35], limited data exist on breast cancer

risk factors or the breast cancer clinical and tumor

marker profile for this underserved population.

The binational nature of the ELLA Study and re-

cruitment of large numbers of women of Mexican

descent in the U.S. and Mexico will provide a unique

opportunity to explore a variety of risk and protective

factors in relation to breast cancer subtypes, including

the cultural impact of the adoption of U.S. lifestyles.

Pike et al. [12] proposed that the lower breast cancer

risk among Hispanic women compared to NHWs is

almost entirely explained by their younger age at first

full term pregnancy, higher parity, low use of HRT,

and low alcohol consumption. These authors also ob-

served a lower risk of breast cancer in foreign-born

than U.S.-born Hispanics. The large proportion of

foreign-born women in the ELLA Study (59%) will

provide unique opportunities to assess residency and

migration history in relation to risk factor profiles and

disease patterns. Our data show that Mexican women

with breast cancer tend to have more children, are less

likely to use contraceptives or HRT, and less likely to

consume alcohol or smoke cigarettes, as compared to

their U.S. counterparts. However, no differences were

shown for age at menarche, age at menopause, or age

at first birth. Data from the South-west Hormone, In-

sulin, Nutrition, and Exercise (SHINE) Study [15,18]

show that a later age at menarche and higher parity

were shown to be protective, whereas a later age at

first birth was associated with higher risk of breast

cancer; however, associations were not all statistically

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Table 3. Characteristics of participants in the ELLA study, March 1, 2007 to June 1, 2009.

Total (N = 765) U.S. (N = 364) Mexico (N = 401)

Age at interview, years, mean (SD) 53.6 (12.6) 51.6 (12.2) 55.5 (12.7)*

Highest level of educationa, No. (%)

Less than high school 376 (53.3) 142 (39.1) 234 (68.4)

High school 187 (26.5) 120 (33.1) 67 (19.6)

Post-high school 142 (20.1) 101 (27.8) 41 (12.0)*

Country of birthb, No. (%)

U.S.-born 150 (41.2)

Foreign-born 214 (58.8)

Nativityb, No. (%)

U.S.-born, living in U.S. ≥ 10 y 137 (37.6)

U.S.-born, living in U.S. < 10 y 13 (3.6)

Foreign-born, living in US ≥ 10 y 163 (44.8)

Foreign-born, living in US < 10 y 51 (14.0)

Language useb,c, No. (%)

English 173 (47.5)

Spanish 191 (52.5)

Age at menarche (y), mean ± SD 12.8 (1.6) 12.8 (1.6) 12.9 (1.6)

Parous, No. (%) 700 (91.5) 334 (91.8) 366 (91.3)

Age at first live birth, mean (SD) 22.9 (5.5) 22.7 (5.6) 23.0 (5.5)

No. live births, mean (SD) 3.6 (2.1) 3.2 (1.8) 3.9 (2.4)*

Ever breastfeedingd, No. (%) 532 (69.6) 210 (57.7) 322 (80.5)*

Up to 9 months 165 (31.0) 87 (41.4) 78 (24.2)

9+ months 367 (69.0) 123 (58.6) 244 (75.8)*

Menopausal status at interview, No. (%)

Premenopausal 334 (43.7) 186 (51.1) 148 (36.7)*

Post-menopausale 431 (56.3) 178 (48.9) 253 (63.1)

Age at natural menopause, years, mean (SD) 48.4 (5.2) 48.7 (4.7) 48.3 (5.4)

Contraceptive usef, No. (%) 416 (55.2) 219 (60.7) 197 (50.1)*

HRT use g, No. (%) 70 (14.3) 49 (23.3) 21 (7.6)*

Prior mammography, No. (%) 470 (61.4) 244 (67.0) 226 (56.4)*

Family history of breast cancerh, No. (%) 91 (12.2) 56 (15.7) 35 (9.0)*

Recent BMIi, mean (SD) 29.2 (6.2) 29.6 (6.9) 28.8 (5.4)

Underweight (< 18.5), No. (%) 5 (0.8) 4 (1.2) 1 (0.3)

Normal (18.5-24.9), No. (%) 163 (24.6) 81 (24.7) 82 (24.6)

Overweight (25.0-29.9), No. (%) 232 (35.1) 105 (32.0) 127 (38.0)

Obese (≥ 30.0), No. (%) 262 (39.6) 138 (42.1) 124 (37.1)

BMI at age 30 yearsj, mean (SD) 24.4 (4.6) 24.7 (4.9) 24.0 (4.3)

Waist circumferencek, cm, mean (SD) 95.2 (14.2) 94.4 (16.6) 95.6 (12.8)

Waist/hip ratiol, cm, mean (SD) 0.88 (0.1) 0.88 (0.1) 0.89 (0.1)

Current cigarette smoking, No. (%) 50 (6.5) 29 (8.0) 21 (5.2)

Alcohol usem, No. (%) 428 (56.1) 228 (62.8) 200 (50.0)*

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Abbreviations: BMI, body mass index; HRT, hormone replacement therapy; SD, standard deviation; U.S., United States; *P < 0.05 comparing differences

between Mexico and the U.S. Differences in means were determined by t test, and differences in proportions were determined by chi-squared tests; P val-

ues are 2 sided; aIncludes 705 participants (363 in the U.S. and 342 in Mexico); bAll Mexican women were born in Mexico had questionnaire administered

in Spanish. With the exception of 2 participants, all foreign-born U.S. women were born in Mexico; cBased on language use during the interview.; dIn-

cludes 764 participants (364 in the U.S. and 400 in Mexico); ePeriods stopped for at least 12 months due to natural menopause, bilateral oopherectomy, or

other reason and age at interview older than mean age of natural menopause; fIncludes 754 participants (361 in the U.S. and 393 in Mexico); gIncludes

women reporting periods stopped for at least 12 months; 488 participants (210 in the U.S. and 278 in Mexico); hFamily history of breast cancer in first de-

gree relatives. Excludes adopted women who reported not knowing their blood relatives and those who reported not knowing whether any family member

had any type of cancer. Includes 746 participants (356 in the U.S. and 390 in Mexico); iWeight (kg)/height (m)2. Defined by self-reported weight and

height 1-3 years prior to diagnosis. Includes 662 participants (328 in the U.S. and 334 in Mexico); jWeight (kg)/height (m)2. Includes 542 participants (296

in the U.S. and 246 in Mexico) and excludes women less than 30 years of age; kIncludes 603 participants (208 in the U.S. and 395 in Mexico); lIncludes

599 participants (207 in the U.S. and 392 in Mexico); mIncludes 763 participants (363 in the U.S. and 400 in Mexico).

significant, and some varied by pre- and post-menopausal

status. Data on the protective effect of breastfeeding have

been published, including the most recent recommenda-

tions from the World Cancer Research Fund/American

Institute for Cancer Research (WCRF/AICR) for breast

cancer prevention [36]. Given the high proportion of

women who breastfed in the ELLA Study (70%), future

studies will be able to explore associations among

women by molecular subtype with higher rates of breast-

feeding than those reported in the literature.

Our data on obesity show that prevalence is equally

high in both countries. Obesity in Mexico is a recent

major epidemic; in 1988, 33.4 % of adults were classi-

fied as overweight/obese and this figure has risen to

71.9% in 2006 [37], with rates higher in women than

men. In the U.S., Hispanics suffer disproportionately

from obesity [38], albeit foreign-born Hispanics have a

lower likelihood of being overweight/obese compared

with those born in the U.S. [39]. Although results of the

SHINE study showed no deleterious effect of obesity for

risk of breast cancer in pre- or post-menopausal Hispanic

women [15], a better understanding of its potential ef-

fects on the distribution of breast cancer specific pheno-

types is needed. Results of two studies found that a

higher BMI and/or a high waist-to-hip ratio was associ-

ated with an increased risk of basal-like breast cancer

[40,41] or triple negative tumors [42]. Data from the

ELLA study will allow us to elucidate the relation of

obesity measures to disease phenotypes for women of

Mexican descent who are disproportionately affected by

high rates of overweight and obesity.

Reports in the literature show that Hispanic women

tend to be diagnosed at a younger age than NHWs [6,

7,43]. Our data based on age at interview are consistent

with these findings. Whether or not this lower age pri-

marily reflects the age structure of the population is un-

clear. In the U.S, Hispanics have a lower median age

compared to NHWs (25.8 vs. 38.6 years) [34] and is

similar to the median age in Mexico (25 years) [44].

Data on tumor stage show that women in Mexico are

diagnosed less frequently with early stage tumors, which

is consistent with published reports from Mexico [45].

Results of our study show lower rates of mammography

screening in Mexican participants compared to those in

the U.S., albeit these are much higher than those re-

ported in national surveys for Mexico [46].

Limitations of our study include the lack of a popula-

tion-based sample. Both countries included largely a

clinic-based recruitment. Given that Mexico does not

have a population-based cancer registry, recruitment for

the study occurred in the IMSS hospitals in all three sites.

IMSS covers approximately 60% of the Mexican popu-

lation by providing care to all formally employed indi-

viduals and their family members. In Guadalajara, two

additional hospitals that serve the unemployed, poorer

segment of the population were used for recruitment.

Thus, in Mexico, patients seeking care in the private

hospital setting are not captured through our recruitment

strategies; however, this is likely to represent only ap-

proximately 5% of the population [47]. In the U.S., re-

cruitment took place at M.D. Anderson, a tertiary refer-

ral center, a county hospital, and a clinic serving indigent

patients and underserved women. In Arizona, cases were

ascertained at the Arizona Cancer Center, county hospi-

tals in Tucson and Phoenix, community health centers,

and other facilities that serve the Hispanic population in

the state.

Results of the ELLA Study show that differences exist

in breast cancer risk factor patterns between Mexico and

the U.S. women. Our experience working with Mexico

has shown that logistics related to recruitment, collection

of medical record data, and tissue retrieval is less chal-

lenging in this country compared to the U.S. Given that

our study includes well-characterized populations, with

comprehensive epidemiological data linked to well-anno-

tated tumor samples and clinical data, future studies will

be extremely valuable in understanding the breast cancer

burden in Mexican and Mexican-American women.

5. ACKNOWLEDGEMENTS

We are indebted to Ana Lilia Amador, Leticia Cordova, Carole Kepler,

and Fang Wang from the Arizona Cancer Center as well as Dr. Alejan-

dro Gómez-Alcalá from the IMSS in Ciudad Obregon, Sonora for their

valuable contribution. We appreciate the support of the Biosciences

Graduate Studies of the Department of Scientific and Technological

M. E. Martínez et al. / HEALTH 2 (2010) 1040-1048

1047

Research of the University of Sonora.

6. GRANT SUPPORT

In the U.S., work was supported by the Avon Foundation, a supplement

to the Arizona Cancer Center Core Grant from the National Cancer

Institute (CA-023074-2953), a grant from Susan G. Komen for the

Cure (KG090934) and a supplement to the M.D. Anderson Cancer

Center SPORE in Breast Cancer (P50 CA116199-02S1). In Mexico,

work was supported by the Consejo Nacional de Ciencia y Tecnología

de México (CONACYT).

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