Recruitment and Retention in Mexican-American Populations

Breast Cancer in Hispanic/Latina Women

Melissa Bondy, Ph.D.Professor of Epidemiology

March 4, 2011

Presentation Outline

Breast Cancer in Hispanic/Latina Women Incidence/morality rates Unique disparities

Breast Cancer Tumor Subtypes The ELLA Binational Breast Cancer Study

Study Objectives Organizational Structure and Milestones U.S.-Mexico Comparisons Recruitment and Retention of Study Participants

Breast Cancer in Hispanic/Latina Women

Female Breast Cancer Incidence and Death Rates* by Race/Ethnicity, Arizona 1999-2001

133.8

26.3

88.8

40.3

62.2

12.4

66.6

17.5

42.7

11.8

0

20

40

60

80

100

120

140

Rat

e/10

0,00

0

NHW Black Asian/PI Hispanic AI/AN

Incidence Mortality*Age-adjusted rates per 100,000Source: Arizona Cancer Registry

Breast Cancer in Hispanics

Hispanic population in U.S. is largely underserved and under-represented in research studies and clinical trials.

The profile of tumor presentation among Hispanic women with breast cancer is consistent with a pattern of more aggressive disease and less favorable prognosis compared to white women: Younger women More likely to have cancer with higher grade More likely to have larger tumors A higher proportion of tumors with later stage A higher proportion of ER- and triple negative tumors More likely to die of their disease than NHWs

No data exist on the prevalence of clinically distinct tumor subtypes (i.e., basal, luminal types).

Refs: Miller, 2002; Li, 2002; Howe, 2006; Bauer, 2007; Martinez, 2007

Breast Cancer in Hispanic/Latina Women

Soraya1969-2006

Thompson and Stopeck, 2008

Compiled from (Millikan, Newman et al.; Carey, Perou et al. 2006; Mullan and Millikan 2007).

Binational Breast Cancer StudyEstudio Binacional de Cáncer de

Mama

Funded by the Avon Foundation andThe National Cancer Institute

US PIs:M. Bondy E. MartinezP. Thompson

Mexico PIs:A. DaneriM. MezaL.E. Gutierrez

What We Would like to Understand

What types of breast cancers are common in women of Mexican descent?

What type of breast cancer occur in women migrating from Mexico to the U.S.?

Is the disease the same in the country of origin?

Are certain risk factors more strongly associated with specific types of breast cancer?

Study Objectives To compare profiles of tumor markers of prognostic and

predictive clinical importance (ER, PR, HER2, Ki67, cytokeratins) between women in Mexico and Mexican-American women in the US (case-case study design).

To assess whether differences in markers are more pronounced by Menopausal status Duration of residence in U.S. or residence status during

adolescence Factors associated with lifestyles more representative of the US

(low parity, late age at first birth, adult weight gain pattern, and body composition).

Additional Objectives

Secondary Objective To determine genetic admixture (i.e., level of population

mixing of European and indigenous American ancestry) to be correlated with the panel of standard tumor markers and other clinical characteristics.

Operational Objectives To strengthen our cancer research collaboration with

investigators at academic centers in the states of Sonora and Jalisco, Mexico.

To enhance capacity for breast tumor immuno-histochemistry among academic medical centers in Mexico, both as a clinical research tool and as an aid to treatment planning.

Binational Breast Cancer StudyEstudio Binacional de Cáncer de Mama

Eligibility and Data Collection

• Eligibility Criteria• Women 18+ years of age• Newly diagnosed with invasive

breast cancer within the last 2 yrs• Mexican descent

• Data Collection• Risk Factor Questionnaire• Medical Record Data• Saliva/blood (DNA bank)

• FFPE tissue collection• Recruitment as of 4/1/10:

• 1075 (480 US, 595 Mexico)

Advisory Committee

→ Steering Committee

Principal Investigators

↓US Sites

MDACC

University of Arizona

Mexico Sites

Universidad of Sonora

Universidad de Guadalajara

Instituto 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 DNAExtraction and

Genotyping

Blood/Saliva DNA Genotyping Statistics

↓ ↓ ↓

↓ ↓ ↓

ELLA Study Organizational Structure

Recruitment

Screened 1871 women from 2007 to present, 1034 of which were eligible for the study

To date, consented 850 patients with 810 actively participating

Received 64 patient refusals at MDACC

Refusals

48 African American (AA) and 16 Mexican American (MA) Historical skepticism and mistrust of the medical research

system in the AA community Barriers in access to care Language barriers Younger Hispanic population (both overall study

population and refusals)

Most common reason given is that the patient is too overwhelmed at time of diagnosis

Other reasons include belief that study gives no direct benefit to the patient, fear of interference with treatment

Reasons for Refusal

Not Interested43%

Too Sick7%

Overwhelmed23%

Family Member Did Not Approve of Participa-

tion10%

Did Not Want Addi-tional Blood

Draws7%

Other10%

Characteristics of Refusals by Race

CharacteristicAfrican-Americans

(N=48)Mexican-Americans

(N=16) p-valueAge <40 Years 5 (10%) 2 (12%) 0.11 40-49 Years 12 (25%) 7 (44%) 50-59 Years 10 (21%) 5 (31%) 60+ Years 21 (44%) 2 (12%)Stage at Diagnosis I 6 (14%) 3 (19%) 0.97 II 16 (36%) 6 (38%) III 16 (36%) 5 (31%) IV 6 (14%) 2 (12%)Subtype ER+/PR+ 28 (58%) 11 (69%) 0.84 HER2+ 6 (12%) 2 (12%) ER-/PR-/HER2- 14 (29%) 3 (19%)Education Less than High School 7 (17%) 6 (46%) 0.02 High School 12 (28%) 5 (39%) Post-High School 23 (55%) 2 (15%)Family History No 34 (72%) 12 (92%) 0.26 Yes 13 (28%) 1 (8%)

Comparison of Refusals and Participants by RaceAfrican-Americans Mexican-Americans

CharacteristicParticipants

(N=402)Refusals(N=48) p-value

Participants(N=386)

Refusals(N=16)

p-value

Age

<40 Years 63 (17%) 5 (10%) 0.02 78 (22%) 2 (13%) 0.68 40-49 Years 111 (29%) 12 (25%) 117 (33%) 7 (44%) 50-59 Years 118 (31%) 10 (21%) 95 (27%) 95 (31%) 60+ Years 86 (23%) 21 (44%) 63 (18%) 2 (12%)Stage at Diagnosis I 43 (18%) 6 (14%) 0.06 48 (24%) 3 (19%) 0.27 II 124 (51%) 16 (36%) 86 (43%) 6 (38%) III 62 (26%) 16 (36%) 62 (31%) 5 (31%) IV 13 (5%) 6 (14%) 6 (3%) 2 (12%)Subtype ER+/PR+ 201 (60%) 28 (59%) 0.37 207 (65%) 11 (69%) 0.63 HER2+ 61 (18%) 6 (12%) 69 (22%) 2 (12%) ER-/PR-/HER2- 71 (21%) 14 (29%) 40 (13%) 3 (19%)Education Less than High School 27 (7%) 7 (17%) 0.06 116 (30%) 6 (46%) 0.19 High School 107 (27%) 12 (29%) 121 (32%) 5 (38%) Post-High School 262 (66%) 23 (55%) 146 (38%) 2 (15%)Family History No 317 (81%) 34 (72%) 0.17 306 (81%) 12 (92%) 0.48 Yes 75 (19%) 13 (28%) 73 (19%) 1 (8%)

Lessons Learned

Employ study staff who are of the same race/ethnicity

Support from physicians who are treating the populations of interest

Study does not require extensive follow up participation

Preliminary ResultsUS-Mexico Comparisons

Sociodemographic Characteristics

U.S. (N=364)

Mexico (N=401)

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

Country of birth, No. (%) U.S.-born 150 (41.2) -- Foreign-born 214 (58.8) --Language use, No. (%) English 173 (47.5) -- Spanish 191 (52.5) --

Reproductive Factors

Characteristic U.S. (N=364) Mexico (N=401)

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

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

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

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

Ever breastfeeding, No. (%) 210 (57.7) 322 (80.5)*

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

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

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

Contraceptive use, No. (%) 219 (60.7) 197 (50.1)*

HRT use, No. (%) 49 (23.3) 21 (7.6)*Women in Mexico women have significantly more children, breast feed more often (and for longer duration), use less OCs and HRT.

Family History and Lifestyle Factors

Characteristic U.S. (N=364) Mexico (N=401)

Fam. history breast cancer, No. (%) 56 (15.7) 35 (9.0)*

Recent BMI, mean (SD) 29.6 (6.9) 28.8 (5.4)

Overweight, No. (%) 105 (32.0) 127 (38.0)

Obese, No. (%) 138 (42.1) 124 (37.1)

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

Waist circumference, cm 94.4 (16.6) 95.6 (12.8)

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

Women in Mexico report a significantly lower percentage of family history of BC

Clinical and Marker DataCharacteristic U.S. (N=350) Mexico (N=399)

Stage, n (%)

I 86 (26) 46 (14)* IIA/IIB 130 (40) 162 (48) IIIA/IIIB/IIIC 89 (27) 118 (35) IV 22 (7) 13 (4)

Tumor markers, n (%)

ER+ 220 (72.4) 161 (58.1)* PR+ 173 (56.9) 155 (56.0) HER2+ 68 (22.4) 65 (23.5) Triple negative 49 (16.1) 57 (20.6)

Women in Mexico have a lower proportion of early stage BCand a lower proportion of ER positive tumors

Family History: How Accurate is Self-Report?

Country of Residence and Level of Acculturation

Family Hx of Breast Cancer

Mexico 9.0%U.S. 15.7% Spanish-dominant 10.8% Bilingual 19.4% English-dominant 23.1%

Summary of Country Differences Significant differences in risk factor profiles observed

between Mexico and the US Parity, breastfeeding, age at menopause, family history of

breast cancer, OC use, HRT. Obesity a major problem for both countries.

Clinical/marker characteristics (preliminary): Younger age at diagnosis in US vs. Mexico Triple negative disease is high in both countries: 16% in US

and 21% in Mexico; difference could reflect variation in lab performance

Factors that Influence Mammography Use and Detection:Findings from the ELLA Binational Breast Cancer Study

RACHEL ZENUK, MPH

R Zenuk1, J Nodora2, S Carvajal1, A Wilkinson4, I Komenaks3, A Brewster4, G Cruz1, BC Wertheim2, M Bondy4, P Thompson1,2, ME Martinez1,2

1University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, Arizona, USA; 2Arizona Cancer Center, Tucson, Arizona, USA;

3Maricopa Medical Center, Phoenix, Arizona, USA; 4M.D. Anderson Cancer Center, Houston, Texas, USA

Breast Cancer Screening Guidelines

ACS recommends: Average-risk women should

receive mammography at age 40 years or older; and

High-risk women receive annual screening mammography and MRI beginning at age 30 years.

USPSTF recommends: Regular biennial screening

mammography should begin at age 50 to 74 years for women at average risk; and

Women under age 50 years should “talk to their doctor” about beginning screening earlier or more frequently than biennially.

Change in Detection Method by Diagnosis Year (N=6074)

Malmgren et al. BMC Cancer 2008 8:131

Significance and Rationale• Compared to non-Hispanic Whites (NHWs), African Americans (AAs) and

Hispanics with BC are diagnosed with more advanced disease resulting in poorer prognosis (Smith-Bindman et al. 2006; Carey et al. 2006; Martinez et al. 2007).

Distribution of advanced-stage invasive tumors among screened women†

42%

55%52%

42%46%

0%

10%

20%

30%

40%

50%

60%

NHW AA Hispanic Asian/PI American Indian

• †Includes 17,558 women from the NCI–funded Breast Cancer Surveillance Consortium with BC who had mammogram between 1996-2002.

Significance and Rationale Younger age, socioeconomic factors, insurance status,

and acculturation/language use have been shown to play a role in knowledge about BC risk and screening mammography receipt; and

Foreign-born women are less likely to know their family history of cancer and receive a mammogram than U.S.-born women

Refs: John et al. 2005; Jacobs et al. 2005; Friedman 2006; Ramirez et al. 2000

Specific Aims

• Specific Aims:• Assess factors that influence screening behaviors

among AA and MA women.• Assess method of BC detection among AA and

MA women

Methods: Study Population and Recruitment

ELLA study population Inclusion criteria:

AA and MA women aged 40-86 years BC diagnosis within last 24 months prior to interview Recruited in U.S. between March 1, 2007 - March 1, 2010

Methods: Data Collection

Medical Record Abstraction Age at diagnosis Stage at diagnosis Insurance status

Interviewer-administered RFQ Sociodemographic characteristics Reproductive history and hormone use Anthropometrics Acculturation (language use/exposure) Breast health history (mammography use and method of BC

detection)

Methods: Data collection Bidimentional Acculturation Scale (Marin and Gamba,

1996) Highly reliable 8-item language-based scale; each item scored

1(never)-5(always) Participants were classified as high or low acculturation using average

cutoff of 2.99 Acculturation groups were:

English LOW English HIGHSpanish LOW Marginalized

reclassified according to interview language

English-dominantscored 3.0 average or above in both English and Spanish

scalesSpanish HIGH Spanish-dominant

scored 3.0 average or above in the Spanish scale

only

Bilingualscored 3.0 average or above

in the English scale only

Mammography use Prior to Breast Cancer Diagnosis

AA (n=28

2)

MA –

English

dom

inan

t (n

=67)

MA -

bilingu

al (n

=173)

MA –

Spanish

dom

inan

t (n=14

8)

55%

60%

65%

70%

75%

80%

85%

79% 76% 76%

66%

Odds Ratios for Mammography Use*

MA - English

MA - bilingual

MA - Spanish

MA - English

MA - bilingual

MA - Spanish

MA - English

MA - bilingual

MA - Spanish

0

0.5

1

1.5

2

2.5

Od

ds

Rati

os

Adj. for age Adj. for age, education Adj. for age, insurance

*Compared to African Americans

Method of Detection among Screened Women

AA (n=217) MA – English dominant

(n=51)

MA - bilingual (n=131)

MA – Spanish dominant (n=98)

0%

10%

20%

30%

40%

50%

60%

70%

57%

47%50%

64%

32%

43%39%

29%

10%6%

9%6%

Self-detected

Mammography-de-tected

Physician-detected by CBE

Other

Delay between First BC Symptom(s) and Seeking Medical Attention

• p<0.001

AA (n=282) MA – English dominant (n=67)

MA - bilingual (n=173)

MA – Spanish dominant (n=148)

0%

10%

20%

30%

40%

50%

60%

70%

80%

62%

72%

64%

46%

26%23%

21% 21%

12%

6%

16%

33%<30 days30-90 days>90 days

Factors Influencing Health-seeking Behaviors

Reasons for prolonging medical attentionone month or more

Discouraged 6%Fear 13%Doctor did not have any earlier appointments 12%Unable to see a doctor due to other commitments 6%Unable to afford or lack of health insurance 31%Did not feel it was important 33%

Study Findings

Differences in mammography use prior to BC diagnosis observed in AA and MA women by level of acculturation are entirely explained by level of education.

Consistent with data in national surveys (70-80% based on BRFSS), AA and MA women in the ELLA Study report high rates of mammography; however, the majority of BC in the ELLA Study was NOT detected by mammography.

17% of women reported delaying more than 90 days between noticing their first BC symptom(s) and seeking medical attention from a health professional; the highest proportion was shown for Spanish dominant patients (33.3%).

Conclusions Given that less acculturated MA women are less likely to have

a usual source of medical care, they are less likely to follow the USPSTF recommendations to “talk to their doctor about screening mammography”.

AA and MA women must be educated about the importance of breast awareness and prompt reporting of any breast changes to a physician or health professional.

Due to the large proportion of self-detected tumors among ELLA Study participants, additional work is needed to assess the degree of effectiveness of screening mammography in these underserved populations.

Ella StudyFuture Directions (N=5000)

Epidemiological Risk Factors:

Reproductive, Obesity, Physical Activity, Cultural

CLINICALPATHOLOGICAL FACTORS, TUMOR SUBTYPES,

AGE AT DX

OUTCOMES (RECURRENCE, SURVIVAL)

Future StudiesGenetic Risk Factors:

BRCA germline mutation,

GWAS hits, Ancestry

X

Summary Unique and tremendous (yet challenging)

opportunities to address breast cancer disparities in Hispanic/Latina women.

Breast cancer rates are lower among Hispanic/Latina women, but unique disparities are evident.

Understanding of complex dynamic between tumor biology (i.e., aggressive disease types) and influence of poverty, culture, access to care (i.e., inadequate treatment) is important.

Essential to involve the communities served.

Acknowledgements

MD Anderson Cancer Center M Bondy, A Sahin, K-A Do, C Amos, A

Brewster, M Edgerton, G Hortobagyi University of Arizona

ME Martínez, P Thompson, AM Lopez, AK Bhattacharyya, ER Greenberg, DS Alberts, R Nagle, R Livingston, I Komenaka

Ventana Medical Systems Anne Lodge, Greg Stella, Eric Walk, Tom

Grogan

Universidad of Sonora/Hermosillo

LE Gutierrez-Millan, G Caire-Juvera (CIAD), E Urquieta-Hernandez, MI Arámbula-Rubio, MA Ortiz-Martínez

Instituto Tecnológico de Sonora/Cd. Obregon

MM Meza, A Gomez Alcalá, MA Ortiz Martinez, JM Ornelas Aguirre, MA Chávez Zamudio, L Pérez Michel

Universidad de Guadalajara A Daneri-Navarro, M Jimenez-Perez, R

Franco-Topete, J Tavares, A Oceguera-Villanueva, G Morgan-Villela, G. Vazquez, MR Flores, A Barragan Ruiz, A Balderas, A Quintero-Ramos

Mexico Health Care Providers Instituto Mexicano del Seguro Social,

Hospital Civil de Guadalajara, Hospital Jaliscience de Cancerología

¡¡Muchas Gracias!!

Variable AA (n=282)MA – English

dominant (n=67)

MA - bilingual (n=173)

MA – Spanish dominant (n=148)

Age at diagnosis, mean ± s.d. 54.9 ± 9.6 55.3 ± 10.9 53.6 ± 9.7 54.4 ± 11.0 *

Private insurance, n (%) 131 (60.7) 32 (62.8) 81 (61.8) 19 (19.4)*

Foreign-born, n (%) 13 (4.8) 9 (13.4) 70 (40.5) 141 (95.3)*

Less than high school, n (%) 21 (7.6) 7 (10.6) 36 (20.8) 106 (72.1) *

Family history of BC, n (%) 53 (20.7) 14 (22.2) 32 (18.9) 15 (10.9)

Oral contraceptive use, n (%) 195 (73.3) 41 (62.1) 118 (68.2) 67 (45.9) *

BSE prior to diagnosis, n (%) 250 (90.9) 54 (80.6) 146 (84.4) 105 (71.0) *

CBE prior to diagnosis, n (%) 239 (87.2) 61 (91.0) 144 (83.2) 102 (69.4) *

Characteristics of Ella Study Population by Race/Ethnicity and Acculturation

*P<0.05