public health democracy: u.s. and global health disparities in breast cancer

7/30/2019 Public Health Democracy: U.S. and Global Health Disparities in Breast Cancer

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Doris Browne, MD, MPH

Public HealtH Democracy:U.S. and Global Health Disparities in Breast Cancer

Global Health Initiative



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Program Director

Breast and Gynecologic Cancer Research Group,

Division o Cancer Prevention, National Cancer Institute

Public Policy ScholarWoodrow Wilson International Center or Scholars

2008

Global Health Initiative

Public HealtH Democracy:U.S. and Global Health Disparities in Breast Cancer


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We live in an age disturbed,conused, bewildered, and araid

o its own orces, in search not merely o its road but even o its

direction. There are many voices o counsel, but ew voices o vision;

there is much excitement and everish activity, but little concert o

thoughtul purpose. We are distressed by our own ungoverned, un-

directed energies and do many things, but nothing long. It is our duty

to nd ourselves.

Woodrow WilsonBaccalaureate address as

President o Princeton University,

June 9, 1907


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u.S. anD Global HealtH DiSParitieS in breaSt cancer

The Woodrow Wilson International Center or Scholars,established by Congress in 1968 and headquartered in Washington, D.C., is a living

national memorial to President Wilson. The Centers mission is to commemorate the

ideals and concerns o Woodrow Wilson by providing a link between the worlds o ideasand policy, while ostering research, study, discussion, and collaboration among a broad

spectrum o individuals concerned with policy and scholarship in national and interna-

tional aairs. Supported by public and private unds, the Center is a nonpartisan insti-

tution engaged in the study o national and world aairs. It establishes and maintains a

neutral orum or ree, open, and inormed dialogue. Conclusions or opinions expressed

in Center publications and programs are those o the authors and speakers and do not

necessarily refect the views o the Center sta, ellows, trustees, advisory groups, or any

individuals or organizations that provide nancial support to the Center.

The Center is the publisher oThe Wilson Quarterly and home o Woodrow Wilson

Center Press, dialogueradio and television, and the monthly news-letter Centerpoint.

For more inormation about the Centers activities and publications, please visit us on

the web at www.wilsoncenter.org.

lee H. Hamilton

President and Director

boarD of truSteeS

Joseph B. Gildenhorn, Chair

David A. Metzner, Vice Chair

Public members: James H. Billington, Librarian o Congress; Bruce Cole, Chair,

National Endowment or the Humanities; Michael O. Leavitt, Secretary, U.S.

Department o Health and Human Services; Tamala L. Longaberger, designated

appointee within the Federal Government; Condoleezza Rice, Secretary, U.S.

Department o State; Cristin Samper, Acting Secretary, Smithsonian Institution;

Margaret Spellings, Secretary, U.S. Department o Education; Allen Weinstein,

Archivist o the United States

Private Citizen Members:Robin Cook, Donald E. Garcia, Bruce S. Gelb, SanderR. Gerber, Charles L. Glazer, Susan Hutchinson, Ignacio E. Sanchez


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acknowleDGementS

The author expresses appreciation and gratitude to Anita Samuel, Woodrow Wilson

Center intern, or her assistance in reviewing articles; to Dr. Carrie Hunter and

Monica Botts or the multiple reviews and suggestions on revisions; to the National

Cancer Institute, Division o Cancer Prevention colleagues or their support; and to the

Woodrow Wilson Centers Global Health Initiative sta, Kai Carter and Gib Clarke,

or their review o and comments on the manuscript, as well as publishing suggestions.

These comments helped to clariy and enrich the nal document.


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contentS

vii Preace

1 Historical Overview

7 Epidemiology

13 Ethno-oncology

15 Migration

17 Socio-economic and Environmental Factors

19 Risk Assessment and Genetic Susceptibility

23 Tumor Biology

27 Molecular Proling

29 Screening and Early Detection

31 Prevention

33 Treatment and Survival

39 Health Systems Disparities

43 Policy ImplicationsClosing the Gap

47 Economic Impact

53 Conclusions and Recommendations

57 Glossary

61 Endnotes


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Public HealtH Democracy


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Preface

The title o this report, Public Health Democracy: U.S. and Global Health

Disparities in Breast Cancer, was selected to highlight democracy (or lackthereo), the primary basis o the United States government system, particularly dur-

ing an election, as well as its application to the public health o its citizens. A unda-

mental test o a nations democracy is the impact o its economy, governance, educa-

tion, criminal justice, and health systems on its people. Public health is more than a

state o general well-being, particularly as it pertains to cancer. It includes how health

services are delivered, who benets, who carries the burden o disease, and how the

costs o illnesses aect our society. This document addresses a major public health

problem in the United States and worldwide that o cancer.

Recent global statistics indicate a rising incidence o breast cancer. Since the war oncancer was declared in the early 1970s, the ocus o the U.S. National Cancer Institute

has been eliminating suering and death due to cancer. We can all be proud o the

technological advances in science and the signicant progress that has been made in the

screening, early detection, and treatment o cancer. Unortunately this progress has not

beneted minorities and the underserved in an equitable ashion, particularly Arican

Americans (AAs). Furthermore, the cancer incidence in developing countries is rapidly

rising. The problem is more than access to care, and is multi-aceted and complex.

This report is intended to synthesize health disparities inormation and increase the

level o awareness and understanding o breast cancer-related health disparities, par-

ticularly in AAs, minorities, and medically underserved women. Furthermore, it wil l

serve as a point o reerence or taking action towards increasing research on the dier-

ences in a subtype o breast cancer that aect the young, AAs, and BRCA1 mutation

carriers at a disproportionate rate.

This country is primed or participating in the democratic electoral process. Let us take

that same enthusiasm to tackle the public health problem o breast cancer health dispari-

ties. For more than three decades we have discussed health disparities, yet the gap be-

tween discovery and delivery o cancer care has either remained unchanged or increased

as health disparities have increased. It is now time to more equitably alter the course o

breast cancer in AAs, other minorities, and the underserved through a democratic publichealth process. Let us not let the past be prologue or the uture o breast cancer care.


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1

Historical overviewsummary

Despite signifcantscientifc advances in cancer research, notall population groups have beneted equally, and broad-range

health disparities persist.

Arican Americans are34 percent more likely to die rom can-cer than non-Hispanic whites, and are twice as likely to die rom

cancer as other minority groups.

Some scientistsdiminish the signicant role that race hason cancer outcomes, solely addressing race as a social construct.

However, it is extremely dicult to disaggregate the impact o race

on cancer outcomes.

In 2007, the National Cancer Institute issued a report indicatinga decline in suering and death rom breast cancer. However, mi-

nority and underserved populations, especially Arican Americans,

showed little or no change.

This paper presents possible solutions to improving the lives oArican American and minority women at risk or breast cancer in

the United States and globally.


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3

Many acknowledge that the diversity o the American population is one o the na-

tions greatest assets, yet there are striking health disparities in the United Statesalong racial, ethnic, and socio-economic lines. Cancer mortality began to rise rom

the eighth-leading cause o death in the 20th century to the second-leading cause in

the 21st century; it is now second only to cardiovascular disease as the leading cause

o death among Americans. The passage o the National Cancer Act o 1971 increased

unding or the National Cancer Institute (NCI), emphasizing training and research

directed toward developing a systematic approach to conquering cancer mortality as

soon as possible.1 Despite signicant scientic advances in cancer research, not all seg-

ments o the U.S. population have beneted rom this progress. A closer look at cancer

rates or racial and ethnic groups reveals signicant dierences in incidence, mortality,and survival that constitute health disparities.

In 1927, the ederal government allocated its rst unding or cancer research, and in

1937, Congress established the National Cancer Institute, which operated with mod-

est unding or several decades. It was not until 1971 that President Nixon declared

a national war on cancer and the National Cancer Act was passed. At that time,

Congress was led to believe that an inusion o unding devoted to cancer research

could produce a cure or cancer beore the American Bicentennial in 1976. Needless

to say, that goal has yet to be achieved. Perhaps the issue is not lack o unding, as

Congress has increased the budget or the National Cancer Institute to more than

$2 bil lion or scal year 2008. Research has primari ly ocused on treatment, but there

should now be at least an equal ocus on environmental actors and preventable causes

o cancer. In addition, the ocus should be on eliminating cancer health disparities in

Arican Americans (AAs) and other minorities, the underserved, and the poor.

Broad-range health disparities still exist today, even though they were well-doc-

umented more than 20 years ago in reports such as the Heckler Report (1985) 2, the

Institute o Medicine (IOM) reports on unequal burden o cancer (1999)3, unequal

treatment (2002)4, health disparities (2006)5, and others. These reports documented

that persistent disparate health status existed in our racial/ethnic groups, dened

by the Oce o Management and Budget guidelines (OMB Circular 15) 6 and theDepartment o Health and Human Services Healthy People (HP) 2000report (1990)7,

HiStorical overview


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4

as AAs, Hispanic Americans, Native Americans/Alaskan Natives, and Asians/Pacic

Inlanders. These reports also outlined the need to improve the health status o mi-

nority populations, as certain racial/ethnic groups experience higher rates o specic

cancers than other groups.

HP 2000indicated that progress was being made in 8 o 17 cancer priority areas.

Yet not all population groups showed benet, especially AAs, who were 34 percent

more likely to die rom cancer than non-Hispanic whites and twice as likely to die

o cancer as other minority groups.8 The mortality rates or cervical and colorectal

cancer in AAs increased, while breast cancer mortality rates were unchanged, when

compared to other racial/ethnic groups. The breast cancer mortality rates or AAs ex-

ceeded the 2000 target o no more than 25 cases per 100,000 people. 9

The HP 2010report indicated that the HP 2000target reduction was met or allcancers, with an overall mortality rate o 27.9 cases per 100,000 or breast cancer.

The 2010 report retained most o the objectives rom HP 2000and added new tar-

gets to urther challenge the United States to obtain better health. The objective or

breast cancer mortality rate was set at less than 27.3 cases per 100,000 or whites and

35.7 cases per 100,000 or AA women (age adjusted to the year 2000 census standard

cHronoloGy of HiStorical eventS in cancer

1971 National Cancer Act (P.L. 92-218)

1973 Surveillance, Epidemiology, and End Results (SEER) program established

1985 Heckler Report outlined health disparities between racial/ethnic minori-

ties and non-minorities

1988 Cancer Prevention Awareness Program directed at high-risk AAs

1990 Oce o Research on Minority Health and Oce o Research on Womens

Health established at the National Institutes o Health (NIH)

1990 Department o Health and Human Services (DHHS) Healthy People 2000

report

1993 NIH Revitalization Act encouraged expansion and enhanced eorts in

breast and other womens cancers

1999 IOM report on unequal burden o cancer

2000 DHHS Healthy People 2010 report

2002 IOM report on unequal treatment

2006 IOM report on health disparities research

2007 NIH Annual Report to the Nation on the Status o Cancer


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5


population).10 Decreasing the number o new cases and deaths rom cancer in accor-

dance with the HP 2010objectives remains an important goal.

In the 2007 National Institutes o Health (NIH) Annual Report to the Nation on

the Status o Cancer, the overall trend in cancer mortality was very positive, continu-

ing a trend started in the early 1990s o an overall decline in cancer deaths in both

men and women o all races.11 The report also indicated an unprecedented improve-

ment in survival, widespread advances in cancer technologies, and a narrowing

gap between discovery, dissemination, and delivery o care demonstrating progress

in the ght against cancer. Unortunately, this very positive trend did not refect

the lack or unevenness o progress that has consistently plagued a large segment

Figure 1. Estimated numbers o new cancer cases (incidence) anddeaths (mortality) in 2002. Data shown in thousands or developing anddeveloped countries by cancer site or emales.

Source: Park in, D.M., Bray, F., Ferlay, J. & Pisani, P. (2005). Global cancer stat istics, 2002. CA: A Cancer Journal

or Clinic ians, 110, 2119-2152.

Incidence

Mortality

514221

16096

700 600 500 400 300 200 100 0 100 200 300 400 600 700500

Breast

Colon/Rectum

Cervix uteri

Stomach

Lung

Ovary etc.Corpus uteri

Liver

Esophagus

Leukemia

Non-Hodgkin

lymphoma

Pancreas

Oral cavity

Thyroid

Kidney etc.

Female

(Thousands)

DevelopingDeveloped

409234

214170

191168

8340

11584

195161

10863

6221

97 62

13629

147143

130110

3638

1615

7559

5838

5538

6834

4340

7238

6017

2614

6568

268

447

3325

636190

312154


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o the U.S. population: racial/ethnic minorities, the poor, the uninsured, and the

underserved.

Today, health disparities persist among minority and underserved populations.

They are maniested as increased mortality, shorter lie expectancy, and higher inci-

dence rates or cancers, inant mortal ity, asthma, diabetes, strokes, and cardiovascular

diseases. Many o the dierences in cancer mortality rates stem rom several actors,

some related to socioeconomic status, ethnicity, and comprehensive therapeutic op-

tions, including lack o or limited access to health care, increased risk o disease due to

occupational and environmental exposure, low socio-economic status, and co-morbid

conditions. Some experts believe the decline in breast cancer deaths in non-Hispanic

whites is attributable to the increased use o screening mammograms, which has led to

detection o the disease in an earlier, more treatable stage. AA women generally have alater stage o the disease at diagnosis, resulting in a greater disparity.

The three IOM reports clearly expressed the need to ensure that the cancer research

requirements o racial/ethnic minorities and the medically underserved are addressed.

The ndings rom these reports suggest that more eective programs targeting re-

sources at identiying the root causes o health disparities were required to reduce the

suering and death o minorities with cancer. Such a comprehensive solution must

be multi-aceted and involve providers, consumers, and health systems managers. The

National Cancer Institutes plan to preempt cancer and to eliminate its il l eects is con-

siderably aggressive; however, such an aggressive pursuit is needed i we are going tomake signicant progress in erasing health disparities between all racial/ethnic groups.

This document is intended to synthesize health disparity inormation and increase

understanding o cancer-related health disparities in AA and Arican women, high-

lighting specic global problem areas in breast cancer. The objective is to stimulate

breast cancer research through the identication and validation o biomarkers or basal-

like breast cancer; to reduce health disparities in AAs at high risk or breast cancer; to

present achievable solutions that can be o use in policy decision making; and to im-

prove the quality o breast health care leading to healthy outcomes or Arican and AA

women. This document will ultimately present possible solutions to the breast cancer

challenges that would improve the lives o AA and other minority women at risk or

breast cancer in the United States and globally. The idea is to recommend achievable

solutions to these challenges as we striveto end cancer orallAmerican citizens.


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7

epidemiologysummary

Cancer is a leading cause o death throughout the world and is amajor public health burden.

Among women, breast cancer is the most common cancer, and isthe second-leading cause o death in the United States behind lung

cancer.

Breast cancer is also the second-most common cancer amongblack South Arican and Nigerian women.

Arican American women have a higher breast cancer mor-tality rate than non-Hispanic white women, despite having lower

incidence rates.

Breast cancer disparities between Arican American and non-Hispanic white women may be due, in part, to an early-onset type

o breast cancer that is over-expressed among Arican Americans.

Early-onset cancers are aggressive, while late-onset ones are more

indolent in behavior.


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Cancer is a leading cause o death throughout the world and is a major public health

burden. The incidence and mortality rates vary among countries and regions o theworld, with the highest rates occurring in developing countries. Recent global cancer

statistics indicate a rising global incidence o breast cancer. This increase is occurring at a

aster rate in populations in developing countries that previously experienced a low inci-

dence o the disease. Among women, breast cancer is the most common cancer and is the

second-leading cause o U.S. cancer death behind lung cancer. The annual global inci-

dence rate o breast cancer cases exceeds 1.1 million each year, representing more than 10

percent o all new cancer cases worldwide and more than 400,000 breast cancer deaths.12

In the United States, 2008 statistics projected 1,437,180 new cancer cases and 565,650

cancer deaths, including 184,450 new breast cancer cases and 40,930 breast cancer deaths.13

Cervical cancer accounts or the highest number o cancer deaths in developing countries,

ollowed by breast cancer (Figure 2). As in the United States, breast cancer is the second

most common cancer in black South Arican and Nigerian women. In Nigeria, the breast

cancer incidence rate increased rom 33.6/100,000 in 1992 to 116/100,000 in 2001.14 In

South Arica, the incidence rate (age adjusted) was 25/100,000 in 1993.15 These gures

were based on diagnoses made through pathology laboratory reports, so they probably

underestimate the incidence rates.

As globalization, liestyles, and longevity change in developing countries, incidence

rates or non-inection-related cancers, such as lung, breast, and colorectal cancers, are in-

creasing. Historically, breast cancer was thought to remain local or a long period o time.

However, breast cancer is a heterogeneous disease and the etiology and prognosis are com-

plicated by many actors. According to the linear model o breast cancer, there is a rapid rise

in incidence rates until the age o 50, then a plateau in incidence rates, ollowed by a slower

ascension (Figure 3).16 This midlie pause is known as the Clemmesens hook, which is

attributable to hormonal changes during menopause and may refect a mixture o two di-

erent incidence curvesone based on age o onset and the other on hormonal-dependent

breast cancer. This theory is juxtaposed against the early-onset estrogen receptor negative

and late-onset estrogen receptor positive breast cancer. Breast cancer has two peak inci-

dences, one around age 50 and the second around age 70. These incidence patterns may belinked to prognostic indicators that are unique or early-onset and late-onset breast cancers.

ePiDemioloGy


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Figure 2. Age at diagnosis o breast cancer by estrogen receptor status:

rate per 100,000; percentage age distribution; and hazard ratio or

mortality rate ater diagnosis.

Source: Anderson, W.F. & Matsuno, R. (2006). Breast cancer heterogeneity: A mixture o at least two main

types.Journal o the National Cancer Institute, 98, 948-951

0.00

0.01

0.02

0.03

0.04

20

51 years

71 yearsClemmesens hook

40 60 80 100

Age at diagnosis

Age distribution at diagnosisAge-specific incidence rates

Density(

densityx100=%)

Ra

tesper100,0

00woman-years

Age at diagnosis

All cases (n=295,257)ER positive (n=180,975)

ER negative (n=53,518)

All cases

ER positive

ER negative

BA

C

2 0 4 0 6 0 8 0 100

0 .1

1

1 0

1 0 0

1 0 00

0.00

0.02

0.04

0.06

0.08

20

2 years

40 60 80 100 120 140

Time in months after diagnosis

Hazard for breast cancer death

Hazardra

tes

All cases

ER positive

ER negative


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Early-onset cancers are aggressive, while late-onset are more indolent in behavior and tend

to parallel the ER-negative (basal-like) and ER-positive (luminal) patterns, respectively.

It is well-documented that AA women have a lower incidence o breast cancer, but a

higher breast cancer mortality rate when compared with non-Hispanic white (NHW)

Americans. This is especially true or postmenopausal women in both racial groups. Yet

there is evidence that young AA women (


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12


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Following the initiation o the war on cancer, a schism developed in the cancer

movement between those who believed there was a need or a national plan oaction and those who opposed such a plan. Independent, uncoordinated cancer re-

search programs have not equally decreased mortality rates or all, especially minor-

ity and underserved populations. Thereore, more emphasis should be placed on the

signicance and implication o thorough cancer research planning that includes all

racial and ethnic groups. One such planning mechanism was elucidated by M. Alred

Haynes, Proessor o Public Health Emeritus, at the 1999 National Action Plan on

Breast Cancer Multicultural Aspects o Breast Cancer workshop, where he coined the

term ethno-oncology.20 It is based on the existence o ethnic groups in the United

States with dierences in liestyle, culture, diet, and environmental exposures. He re-erred to ethnic group as a social construct characterized by distinctive social, cultural,

and belie traditions maintained within the group rom generation to generation; a

common history o origin; and a sense o identication within the group. Members o

the group maintain distinctive ways o lie, shared experiences, and common heritage;

these eatures may also be maniested in their health and disease experiences.

The eld o ethno-oncology seeks to learn as much as possible about the causes o

cancer by exploring dierent maniestations o cancer across ethnic groups. The ge-

netic boundaries that were once thought to separate minorities rom the majority do

not really exist, and racial classication does not provide a very rm basis or cancer

research. There is, however, much to be learned by ocusing on the cultural and ge-

netic heritage o racial and ethnic groups. This also requires an accurate data set o sta-

tistical inormation rom which to draw viable conclusions. Although some theorists

contend that cancer is due to genetic changes 100 percent o the time, genetics is not

always the cause o cancer. The role o the environment remains unclear.

It is critically important to have accurate statistics to draw reasonable conclu-

sions on cancer etiology. However, existing data is limited and does not allow or

standardized racial admixtures. There is much to be learned rom ocusing on cul-

tural and genetic heritage o racial/ethnic groups. Currently, health data collection

is based on sel-identied racial and ethnic groups. Several studies have advancedthe identication o race and ethnicity by using molecular marker analysis to show a

etHno-oncoloGy


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lineage relationship between genetic short tandem repeats and single nucleotide poly-

morphism (SNP). This results in the identication o population groupings worldwide

that is consistent with the primary racial and ethnic groups in the United States, such

as Arican American, Caucasian or NHW (European and Middle Eastern), Asian,

Pacic Islander, and Native American. Racial admixtures also provide another avenue

or examining molecular and genetic markers in dierent population groups.


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15

Cancer is a worldwide problem, but it maniests di erently in dierent parts o the

world.Breast cancer is very common on the continent o Arica, second only tocervical cancer in Arican women. Whilebreast cancer cases seem to have stabilized in

many developed countries, they continue to rise in developing countries. Reasons or

this continuing r ise in developing countries have been ascribed to changes in demog-

raphy, socio-economic status (SES), and dierent epidemiological risk actors. The

incidence rates and requency o breast cancer in Arican women tend to peak earlier

than in NHWs by at least a decade. This is potentially conounded by a lower lie ex-

pectancy o 45-55 years in Arica, as compared to 75 years or NHW in the United

States. Young women presenting with advanced-stage breast cancer is more the rule

than the exception in Nigeria and other Arican countries; generally, the breast lumpis accidentally discovered, as there are very limited mammography programs and a

lack o screening and awareness campaigns. Thereore, the stage o the disease at pre-

sentation is refective o breast cancer awareness in the general population.

Young women who are still menstruating have been ound to have the highest breast

cancer incidence rates in Nigeria and in AAs in the United States. In a Nigerian study,

75 percent o the cases had only gender and age as risk actors.21 Another Nigerian

study ound that 19 percent o women were pregnant or lactating at presentation and

that 80 percent o women in the study had advanced stage cancer.22 Risk actors and

reproductive behavior, such as early age at rst birth, which play a role in U.S. inci-

dence, may not apply in Arican communities. Arican women are characterized by

high ertility rates and multiparity. Studies have ound associations between breast-

eeding, multiparity, and breast cancer in Arican women. 23 24 Dierences have also

been shown in the incidence rates in urban versus rural populations.

The eect o migration and migration patterns have been studied as possible contribu-

tors to the higher mortality rates, including migrations rom Arica to the United States

and southernnorthern migration within the United States. One study postulated that

there might be a migration gradient that interacts with the length o stay in an urban en-

vironment. The role o genetics, liestyles, and childhood exposure to environmental haz-

ards play a signicant role in breast cancer risk, but is modied when migration occurs.25Several studies have looked at the migration o people rom several Arican countries to the

miGration


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United States and the dierences in their cancer risk. Arican women tend to present with

late stage disease, and the cancer is an aggressive type similar to that observed in young AA

women. The late stage at presentation links directly to lack o screening programs, poorcancer education and knowledge o sel examination, inadequate medical acilities, and

ailure to seek medical attention ater traditional and local methods have ailed.

Studies have also addressed migration rom the southern United States to the north-

ern United States, as well as migration rom rural to urban areas.26 The data on south-

to-north migration indicated that native northern AAs had higher cancer incidence rates

than southern natives. However, rural-urban dierences also existed or breast cancer,

where the ratios were slighter higher or southern urban natives. A study by Greenberg

and Schneider in 1995 indicated that southern-born AAs who moved north had greater

cancer mortality rates, in contrast to the low rates seen in oreign-born blacks.27

Anotherstudy reviewed the dierences in cancer risk among childhood and adult migrants and

compared them to native-born AAs; the conclusions armed that there is a regional di-

erence in breast cancer proportional to the incidence rates seen in these racial groups.28

However, other actors, such as occupation, SES, environment, liestyle, and access to

medical care also play a role in breast cancer outcomes.

Mobility o immigrants once they have arrived in the United States is also an issue

worth exploring. According to 2000 census data, oreign-born persons accounted or

24 percent o two or more races o those responding to the census survey; 6.1 percent

o AAs, 3.5 percent o NHWs, and 40 percent o Hispanics were oreign-born.29 U.S.

oreign-born populations increased by more than 50 percent between 1990 and 2000.

The number reporting Latin American, Arican, and European ancestries more than

quadrupled during the same decadeor instance, the Arican population grew rom

246,000 to 1.2 million. AA and Mexican ancestry were the most commonly reported in

the ten largest cities. O this number, 16 million were rom Latin America, representing

52 percent o the total oreign-born population. Only about three percent were rom

Arica (Figure 6). The mobility rate (changing o usual residence) or Aricans once in

the United States is 68 percent. Understanding migration patterns o the oreign-born

U.S. population is becoming increasingly important as the patterns o migration may

hold some signicance, not only or population growth issues, but also on health care

requirements and consequent economic impact.

Figure 4. Percent distribution o oreign-born

population by world region o birth: 2000

(Data based on sample. For inormation on confdentiality

protection, sampling error, nonsampling error, and defnitions,

see www.census.gov/prod/cen2000/doc/s3.pd.)

Note: Adds to 99.9 percent due to rounding.

Source: U.S. Census Bureau, Census 2000, Summary File 3.

Central

America

36.0Latin

America

51.7

Caribbean 9.5

South America 6.2

Asia

26.4

Europe

15.8

Africa 2.8

Northern America 2.7 Oceania 0.5


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Cancer is infuenced by both environment and genetic actors; nevertheless, the

direct infuence o various environmental triggers on genetic actors has notbeen well-delineated. Because o the mutational spectra within breast cancers o

women rom dierent racial and ethnic backgrounds, p53 mutations are present in

a signicantly higher proportion o transitional-type mutations among tumors in

AA women when compared with NHW women.30 Although AA women are more

likely to have low SES, based on education, amily income, and occupation, many

have better health coverage because o public insurance programs. Despite this, AA

women are signicantly more likely to be diagnosed with later-stage cancer, with

54 percent o AA women diagnosed with ER-negative tumors as compared to 39

percent o NHW women.31

There are many reasons proposed or the dierences in breast cancer seen between

AA and NHW women. High mortality rates in conjunction with low incidence rates

and low survival rates were previously believed to be the result o late-stage diagnosis

and lack o access to health services. Today, we recognize that while access and SES

actors are important, there are many other actors that must be considered. One study

researched cultural reasonsincluding customs, norms, values, belies, language, and

health systemsdriving the high mortality rates and low survival o AA women with

breast cancer.32 The study ound that ear, hopelessness, atalism, and disease percep-

tion all infuenced the ability and willingness o AA women to seek screening, diag-

nostic, treatment, and preventive services in an appropriate and timely manner.

A signicant percentage o AA women are infuenced by popular myths about

breast cancer. For instance, many believe that breast cancer is a white womens disease;

that traumaincluding surgeryprovokes the outgrowth o the cancer, causing the

primary tumor to grow and metastasize; and that i a woman does not know she has

breast cancer, it will disappear. These are some o the myths that infuence 61 percent

o AAs and 29 percent o NHWs in the United States.33 These perceptions lead to a

delay in seeking medical care and ollow-up. Peer education has been eective in cor-

recting some o these alse perceptions and minimizing the ear o cancer. Education

has resulted in a sense o empowerment or AA women, providing them with a moreproactive role in their health status.

Socio-economic anD

environmental factorS


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Known risk actors or breast cancer include increased age, personal and amily

history o breast cancer, atypical hyperplasia, early onset o menarche (< age 12),late age o menopause (> age 50), and rst live birth ater age 30. Other risk actors,

such as hormone replacement (estrogen/progestin) therapy, ionizing radiation, alcohol

consumption, and obesity have also been correlated with increased breast cancer risk.

Increased breast density, high at diet, little or no exercise, and (possibly) electromag-

netic elds may also play a role.

One theory regarding the origin o breast cancer is that it arises rom a series o

genetic events linked to morphologic changes in cell progression. Another theory

postulates that breast cancer evolves in normal ductal tissue through a series o

changes that result in cancer. Estrogen has been associated with molecular changesin breast tissue and plays a signicant role in breast carcinogenesis. Estrogen is im-

portant because it acts as a highly potent mitogen to normal breast epithelial cells.

Many believe that the length o exposure o the breast epithelium to estrogendeter-

mines its role in the development o breast cancer. Thereore, the duration and level

o estrogen exposure are very signicant risk actors or breast cancer. The age o

onset o menses and menopause, the age o rst l ive birth, and the number o preg-

nancies are all reproductive risk actors that are directly related to estrogen expo-

sure. Hyperplastic changes commonly occur in the breast; however, the progression

to cancer occurs in only a small percentage o the breast. Breast cells progression

rom normal to premalignant hyperplasia and then to in situ carcinoma is thought

to be the result o estrogens eect on the cell and the result ing mutation eect on

the receptor cells.

Between ve and 10 percent o breast cancers are caused by mutation in the breast

cancer genes, BRCA1 or BRCA2. The BRCA gene mutation is more likely to occur

at a young age, in ER-negative tumors, and in an environment where other gene in-

teractions play a role. The BRCA1 gene mutation corresponds with the high incidence

o cancer seen in AA women between the ages o 30-49. BRCA1 mutation cancers are

poorly dierentiated, have high S phase raction, medullary or atypical histology, high

p53 mutations, and are ER-negative/PR-negative. A similar pattern is seen in youngAA women who exhibit polymorphisms and other variants.34

riSk aSSeSSment anD

Genetic SuScePtibility


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Childbearing seems to have a dual eect: Early age (younger than 30 years) at rst

live childbirth is protective. Multiple births at a young age (prior to age 45 years) may

increase breast cancer risk; however, it is protective against breast cancer ater age 45.

A study by Pathak indicated that the increased risk or breast cancer in AA women

may be due to the higher prevalence o early childbearing in AA women compared

to NHW women.35 The typical prole o Nigerian women with breast cancer is con-

sistent with that o other developing countries, in that they are generally multiparous,

premenopausal, and have prolonged breasteeding. In a 10-year review o Nigerian

women, the mean parity was 5.35, the age at rst ull term pregnancy was 20 in 57

percent o cases, and breasteeding continued or a mean o 8-12 months.36

The ability to determine i a women is at high risk or acquiring breast cancer is

based on the presence o several known risk actors. Mitchell Gail o the NationalCancer Institute developed a risk assessment tool, known as the Gail model, which is

designed to determine the eligibility o a woman to participate in cancer clinical tri-

als.37 Data or this model were based primarily on NHW women, and the useulness

and applicability o this model or AA women has been challenged by several groups.

The Claus model was developed using some o the criteria rom the Gail model, with

additional modications in an attempt to have greater applicability or AA and other

minorities.38 The number o AA women in clinical trials remains small, as the eligibil-

ity criteria (based on number o rst-degree relatives with breast cancer, age at menar-

che, age at rst live birth, and number o breast biopsies) exclude many women whoare interested in participating in such trials. The Study o Tamoxien and Raloxiene

(STAR) trial is an excellent example o the increased interest o AA women in par-

ticipating in a cancer prevention trial. In this study, 20,278 AA women were screened

and completed the risk assessment tool. However, only 2.5 percent (488) were deemed

eligible to participate in the study o 19,747 women.39

In 2007, Gail and his team o researchers developed a new risk assessment tool to

more accurately predict the breast cancer risk o AA women, using data rom the SEER

program and the Womens Contraceptive and Reproductive Experiences (CARE)

study.40 The CARE study involved a comparison o 1607 AA women with invasive

breast cancer and 1637 AA women o similar age without breast cancer. Factors used to

create this new model were age at rst menarche, number o rst degree relatives with

breast cancer, and number o previous benign breast biopsies. Age at rst live birth was

not identied as a predictive actor o signicance in AA women. Risk was calculated

by combining the above actors with the rates o invasive breast cancer and mortality

rates in SEER. The outcome o the CARE model was validated using two risk pro-

les. One group consisted o AA women in the Womens Health Initiative study with

no history o breast cancer. The comparison group was AA women who were screened

or the STAR trial, but were deemed to be ineligible.

The results revealed that the risk or invasive breast cancer in AA women was 30.3percent based on CARE, compared to 14.5 percent based on the Breast Cancer Risk


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Assessment Tool that determined previous eligibility or the STAR trial and other

cancer studies. This is a major step orward in determining breast cancer risk in AA

women. Nevertheless, it is important to recognize that this tool may be inappropriate

or all minority women and certainly has no benet or women with a prior history

o breast cancer. Moreover, it may not provide an accurate prediction or women with

the breast cancer gene mutation or who have been exposed to radiation treatment.

While the CARE model is eective in AA and other minority women, it still needs

urther validation.

Genetically engineered animal models can provide important venues or analyzing

prevention and treatment mechanisms. Such models could serve as useul preclini-

cal testing grounds or potential interventional agents, as well as predictive models

or human response. Recently, research has compared the gene expression proleso mouse mammary tumors and human breast cancers. For instance, a UK research

group perormed an engineered mouse model or basal-like carcinoma expressing

the triple-negative phenotype using BLG-Cre, BRCA1, and p53. The BRCA1 gene

was inactivated in luminal epithelial cells o mouse mammary gland, and all cells

had one wild-type allele o p53. The analysis o tumors arising in these mice was

consistent with human tumors that were ER-negative/HER2-negative, expressed

basal markers 78 percent o the time, and had 88 percent homologous metaplastic

elements. This model may provide the necessary link between basal-like phenotypes

and BRCA1 pathways, as well as prove useul or testing novel therapy or humanbasal-like cancers.41 This work is similar to work perormed in the United States by

Green at the National Cancer Institute (NCI), who perormed a genomic analysis

o the T antigen mouse model and identied a gene expression signature contain-

ing many genes involved in prolieration, DNA repair, metabolism, cell cycle, and

apoptosis.42 The T antigen signature is similar to what is seen in human basal-like

tumors and is predictive o survival in breast cancer patients. The applicability in AA

women has yet to be validated.


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tumor Biologysummary

Statistically signifcant characteristics o breast tumors inArican American women include later stage at diagnosis, larger

size, positive lymph nodes, higher histologic and nuclear grade, and

aggressive growth. These result in poorer overall survival rates.

Arican Americanwomen are diagnosed twice as oten asnon-Hispanic whites with advanced stage breast cancer with poorly

di erentiated nuclear grade.

Mutations inp53 and c-met both result in negative prognosesor women, and Arican American women are signicantly more

likely to have tumors with these mutations.


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Generally, AA women have a lower incidence rate o breast cancer than their

NHW counterparts. However, young AA women (< age 45) have higher in-cidence rates. The disease in AAs is more aggressive and usually presents earlier as

high grade histology with estrogen receptor negativity, resulting in a poorer overall

survival rate. Many studies conrm that AA women tend to have breast tumors with

high-grade nuclear atypia, high mitotic activity, higher S phase raction, poor dier-

entiation, ER-negativity, and progesterone receptor (PR) negativity. Mutations in p53

and c-met both result in negative prognoses or women, and AA women are signi-

cantly more likely to have tumors with p53 mutations and c-met positive tumors, even

when adjusted or age and other conounding actors.However, conounders such as

ER- and PR-negative hormone status and obesity may skew the potential associationbetween c-met expression and mortality rates in AA women. A study by Poola et al re-

vealed that a beta isoorm expression in the estrogen receptor,which may be protective

against prolierative changes in mammary epithelial tissue, may be disproportionately

low in AA women.43 Other biomedical studies have ound that hormone-receptor

negative, aneuploidy, and node positive breast cancer appear to be specic to AA breast

cancer, even ater controlling or stage at diagnosis and age.

Demographics o Aricans and AAs, such as younger age at presentation and dietary,

genetic, and environmental actors, may independently or simultaneously infuence the

biological and clinical patterns o breast cancer observed in these groups and contrib-

ute to the aggressiveness o the disease and poorer outcomes. One Arican study ound

that ater adjusting or these actors, the results were similar to U.S. studies where AA

patients had higher mitotic activity and nuclear grade atypia.44 The higher prolierative

activity may be partially explained by several actors, such as the prevalence o obesity,

which is associated with high plasma estrogen levels. Obviously, the concept o tumor

biology should be used to aid in predicting the outcome o breast disease.

Several studies45464748 have shown that younger women tend to have breast carci-

nomas that are endocrine negative, have poorer outcomes, and have higher local ail-

ure rates ollowing surgery. While these tumors may be smaller, they are biologically

more aggressive, with high vascular potential and a greater probability o regionalnodal metastases. Statistically signicant characteristics in the breast tumors o AA

tumor bioloGy


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women include later stage at diagnosis, larger size, positive lymph nodes, higher histo-

logic and nuclear grade, and aggressiveness o growth. These same characteristics have

also been seen in studies o young Arican women. Factors infuencing late presenta-

tion include religious belies, denial, SES, herbal treatments, ear, unriendly hospital

atmosphere, preerence or indigenous or non-allopathic healers, general lack o breast

cancer awareness, and, in some cases, a lack o knowledge among primary health care

providers about breast cancer.

Increased breast cancer awareness has led to greater use o mammograms and may

be partially responsible or the increase in the presentation o ductal carcinoma in

situ (DCIS) cases. One study o premenopausal women (ages 1935 years) ound a

DCIS correlation in most o the invasive cancers, which may indicate that a pathogenic

mechanism in the pathway to invasive breast cancer progressed through an in situ phasein these young women.49 These ndings suggest that biological changes progressing

toward the development o breast cancer start very soon ater puberty.The presenceo

intermediate to high nuclear-grade DCIS elements was used to explain the rapid inva-

sion into the stroma observed in this study.

The pathologic predictive indicators or HER2/neu gene amplication and/or

over-expression also seem to dier or AA women and NHW women, but are not

likely to explain the survival dierences between the two groups. AA women are

diagnosed twice as oten as NHW women with advanced-stage breast cancer that has

poorly dierentiated nuclear grade.


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Molecular proling is a tool used or better classication o cancer origins; it ulti-

mately aids in providing a more accurate prognostic and therapeutic selection.The mechanism identies sets o genes whose expression classies breast cancer into

distinct intrinsic subtypes and allows or an association with survival. Molecular prol-

ing allows the comparison o di erent tissue types on a molecular level to a global scale

through the use o two primary techniques, one supervised and the other unsupervised.

The supervised technique uses sample groups that have known clinical outcomes in

order to generate gene expression data that is useul in determining dierences in gene

expression within the known outcomes group. The unsupervised method character-

izes samples into sub-classes through di ering gene expressions rom a cohesive set o

samples. The goal o molecular proling is to identiy a distinct subset o breast cancerthat will be helpul in determining the variability o response to treatment and clinical

outcome. Because o the heterogeneous nature o breast cancer, molecular proling

has lead to subsequent identication o ve intrinsic subtypes: Luminal A, Luminal B,

normal, HER-2 over-expressing, and basal-like. Dierentiation into these sub-types

is based on a comparison o gene expression data rom the unknown sample with

known expression controls.

O the ve subtypes, two are estrogen receptor-(ER) negative tumors: the basal-

like and HER2-positive/ER-negative. The HER2-positive/ER-negative subtype is

characterized by an over-expression o a HER2-related cluster o genes. The basal-

like subtype is characterized by low expression o HER2-related genes, but a high

expression o a group o genes having characteristic o normal basal epithelial breast

tissue. These basal cells stain with antibodies to cytokeratin 5/6, 14, and 17; BRCA-1

gene mutations; and have higher prolieration rates, aggressive histology, and unavor-

able clinical outcomes. Evidence suggests that the basal-like type is a distinct subtype

o invasive carcinoma. They are also characterized by ER negativity, PR negativ-

ity, HER-2 negativity, BRCA-1 mutations, high-grade nuclei, mitotic index and ag-

gressive histology, shorter survival, p53 over-expression, unsupervised gene expres-

sion proling, and a lack o response to endocrine therapy. This histologic subtype is

most oten consistent with the ductal, but medullary or non-specic cell types havealso requently been seen. Because o the earlier age at diagnosis (more prevalent in

molecular ProfilinG


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premenopausal women), higher tumor grade, and greater proportion o basal-like

(ER-, PR-, HER2-) tumors, researchers suggest that this type o breast cancer is more

commonly seen in AA women and is biologically dierent.

Studiesshow that 80-90 percent o triple-negative carcinomas are basal-like and are

characteristic o mouse stem cells. There are also ndings that subtypes are aliated

with mammary cells o origin, indicating that changes in gene expression patterns may

be associated with carcinogenesis occurring early in the cell progression process.50 One

study identied 10-17 percent triple-negative carcinomas, which is comparable to the

reported incidence o basal-like cancer. Using triple-negative as a surrogate marker or

basal-like breast cancer reveals that pre-menopausal AA women are a high-risk group

and that there is a biologically distinct negative survival correlated with having the

triple-negative phenotype.51In order to characterize triple-negative (ER-, PR-, HER2-) phenotypes with re-

gard to age, ethnicity, SES, and survival, a population-based study observed all new

invasive breast cancer cases in 92,358 women in the Caliornia Cancer Registry be-

tween 1999 and 2003.52 Using micro-array proling, 13 percent (6370 cases) were

identied as triple-negative phenotypes, with 63 percent being diagnosed beore the

age o 60. The percent o AA women with triple-negative phenotypes was twice that

o other racial and ethnic groups. Approximately 85 percent o triple-negative breast

cancers were basal-like, although all basal-like tumors are generally triple-negative.

Reports indicate that women with higher SES tend to have higher breast cancer in-cidence and smaller tumors.53 The median tumor size is generally larger in women

with the triple-negative phenotypes and the primary histology is classied as poorly

dierentiated or undierentiated. Women under age 40 are 1.53 times more likely to

develop triple-negative cancer than those women age 60 or older. Survival rates are

also lower or women with triple-negative, with only 77 percent o women surviving

beyond ve years in comparison to 93 percent survival rates or other subtypes.

A population-based study involving 196 AA women and 300 NHW women con-

cluded that despite the presence o all the subtypes in both populations, there was an

interaction between race, age, and subtype.54 Basal-like tumors were present in 39

percent o the AA population and probably impacted the poor outcome or the AA

cohort. Genetic and biologic variation in cancer gene expression is evidenced in the

higher mortality rates coupled with low incidence rates generally seen in AA women.


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Population-based, single-institutional, multi-center, and meta-analysis studies have

shown that AA women o all ages tend to present with advanced stage diseasecompared with NHW women. Failure to present with early stage disease is consis-

tent with the absence o optimal screening practices by AA women. Screening rec-

ommendations rom the NCI, American Cancer Society (ACS), and the National

Comprehensive Cancer Network (NCCN) in the United States include an annual

clinical examination and mammogram and monthly breast sel-examinations, with

40 as the baseline starting age. Mammography may be started earlier in high-risk in-

dividuals, as decided by the patient and the health care provider. However, data rom

ACS reveal a statistically insignicant dierence in mammography screening utiliza-

tion between NHW (70 percent) and AA (67 percent) women. Obviously, other ac-tors impact the late stage at diagnosis prevalent in AA women.

Screening and early detection are paramount to improved outcomes and increased

survival rates in AA women. National Health Interview Survey (NHIS) data shows

an increase in screening mammograms among both AA and NHW women, indicat-

ing a usage rate o 68 and 71 percent, respectively, or those over age 50. For women

age 40-49 years, usage is 61 and 67 percent, respectively.55 However, studies ocusing

on SES ound that outcome disparities will not be eliminated entirely by intensive

screening eorts alone.56One report showed that even ater adjusting or SES, stage,

and age at diagnosis, AA women had a 22 percent higher mortality risk.

In Arican countries like Nigeria, where mammography is a scarce resource and

there are no recommended guidelines, most subjects present with large tumors involv-

ing extensive skin pathology o the whole breast (26 percent) and axillary nodes (84

percent).57 Experts propose that using the count o mitotic gures as a prognostic tool

is a less expensive and more cost-eective diagnostic method or Nigeria.

ScreeninG anD early

Detection


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There is a critical need to develop innovative strategies or preventing and treating

breast cancer in order to identiy a more comprehensive approach to reducingthe disproportionate number o breast cancers in AA women in particular, but also to

eliminate breast cancer health disparities more broadly. Cancer chemoprevention uses

either naturally occurring or synthetic chemical agents to prevent, reverse, or arrest

the progression o preneoplastic lesions to invasive breast cancers. The progression

rom normal, preneoplastic, dysplasia, hyperplasia, in situ to invasive cancer may also

be blocked rom progressing by inhibiting epithelial mutagens and mitogens. This can

occur when modication or prevention o carcinogenesis steps takes place by prevent-

ing DNA damage rom ree radicals, decreasing epithelial cell prolieration, and/or

increasing dierentiation.An investment in cancer prevention research that began in 1998 with the initiation

o the rst breast cancer prevention trial (BCPT) demonstrated an eective agent or

the reduction o breast cancer incidence among high-risk women. The study results

showed that tamoxien, a selective estrogen receptor modulator (SERM), caused a 49

percent reduction in invasive breast cancer in high-risk postmenopausal women and

an overall reduction o 50 percent in the incidence o breast cancer in pre- and post-

menopausal women.58 This oers proo o principle or targeting the estrogen recep-

tor in ER-positive breast cancer. The STAR (Study o Tamoxien and Raloxiene)

Trial in 2006 yielded consistentresults in urther advancing ER-positive breast cancer

preventionby showing a second SERM,raloxiene, to be equivalent totamoxien in

preventing breast cancer, but with lessserious toxicity.59It demonstrated a preventive

eect or invasive breast cancer in high-risk postmenopausal women, and in 2007,

this agent became the second breast cancer prevention agent approved by the U.S.

Food and Drug Administration or human use. In act, the overall reduction refects a

70 percent reduction in ER-positive disease, but no reduction in ER-negative breast

cancerleavinga major gap in breast cancer prevention.Denitive Phase III cancer

prevention trials based on cancer incidence are intensive in their requirement or clini-

cal resources and will become more dicult to und in the uture.

However, an attractive way to study potentially useul chemopreventive agents isto perorm short term (pilot or Phase 0) studies examining the eect o interventional

Prevention


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agents on molecular, imaging, and histologic surrogate endpoints o disease status in

populations at high risk or developing invasive cancer. A clinical opportunity or

prevention o ER-negative (basal-like) breast cancer presents itsel in using this pre-

surgical model in women with an initial diagnosis o ER-negative cancer on biopsy

specimens that require a denitive excision procedure. Investigators might consider

smaller studies that measure biomarkers o interest (or example, HER2/neu). Prior

to denitive surgery, the eect o a single or multiple dose oral agent with prospects

or prevention could be given. Following excision, a measurement o targeted tissue

or biomarkers would be obtained and compared with placebo to determine pharma-

cokinetic measures and changes in concentration o the molecular targets o interest

(or example, progenitor cell characteristics) in the denitive excision material. This is

the model used previously in preclinical or animal studies to determine the ecacy ochemoprevention agents.

Due to advances in molecular biology, promising agents or chemoprevention stud-

ies in ER-negative breast cancer may be discovered, such as kinase inhibitors (e.g.

Epidermal Growth Factor Receptor (EGFR) or Kit) and rexinoid (RXR) agonists,

which may interact with multiple nuclear receptors, anti-infammatory and anti-an-

giogenesis agents, Vitamin D analogs, Poly ADP-ribose polymerase (PARP) inhibi-

tors, or a combination o these agents. One such example may be kinase inhibitors

activity targeted at EGFR1 and HER2/neu, which might reduce the risk o develop-

ing ER-negative breast cancer. For BRCA1 mutation carriers who are diagnosed withER- negative breast cancer, biomarker studies need to be organized with a ocus on

drug modulatable targets.


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treatment and survival summary

Some reasons or the racial/ethnic disparities in survival are di-erences in treatment utilization, co-morbid conditions, insurance

coverage, and/or provider biases.

Arican Americanwomen tend to obtain appropriate primarytreatment (surgery), but not adequate adjuvant chemotherapy.

While theUnited States is starting to address the impact obreast cancer as the leading cause o death in younger women,

Arican countries have not, and the ravages o this disease continue,

due to poor health conditions and inadequate health care acilities.

In Nigeria and other Arican countries, breast conserving op-tions are not readily easible, due to late-stage presentation, lack o

adequate radiotherapy acilities, ew diagnostic oncology specialists,

inability to characterize prognostic actors, young age o patients, and

poor ollow-up.


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Large prospective randomized, controlled trials have shown that adjuvant therapy

is an integral component o breast cancer early stage management, even or ER-negative disease. Such treatment has led to an increased rate o survival. Even in

areas where there are multi-disciplinary teams o breast cancer providers, large dis-

parities exist in the provision o appropriate adjuvant treatment (i.e., under-use o

ecacious adjuvant treatment was 16 percent or NHWs versus 34 percent or AAs

in a New York study).60 Poor survival continues to occur in AA and other minority

women. The reason or this poor survival is not well-dened. In part, it may be due

to the severity o the disease, larger tumors, and late stage at diagnosis. Some reasons

or the racial dierences in survival are disparate treatment utilization, co-morbid

conditions, insurance coverage, and/or provider biases. While AA women seem toreceive appropriate primary treatment (surgery), they do not receive adequate ad-

juvant chemotherapy, and when the accompanying co-morbid conditions are con-

trolled or, the disparity in treatment continues to persist. One study ound that AA

women do not receive recommended oncology consultation, which leads to missed

opportunities or optimal treatment and may partially explain the poorer survival.

Enhanced communication between patients and providers may help in reducing ra-

cial dispar ities in cancer care. Improving the overall quality o breast cancer care and

ensuring that AA women receive the required intensive treatment is a cost-eective

way to decrease the mortal ity di erential. 61

Despite the poor prognosis o basal-like and HER2+/ER-negative subtypes, they

demonstrate high rates o pathologic complete response (pCR) when treated with

neoadjuvant chemotherapy and may benet more rom chemotherapy than Luminal A

tumors, according to results rom a study by Morris and Carey.62 Negative associations

o triple-negative phenotype with survival disappeared in the group receiving chemo-

therapy, which indicates better response to this orm o therapy. Analyses o survival

ound that nodal status, tumor size, and negative androgen receptor status correlated

with reduced disease-ree intervals and overall survival. However, nodal status and size

were the only markers with independent prognosis signicance. Less than 10 percent

o ER-negative, PR-negative tumors respond well to chemotherapy. There are limited

options or treatment o triple-negative tumors, which require additional biomarkers

treatment anD Survival


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36

to be more clearly characterized as a subgroup. There are no known specic targets

identied in tr iple-negative breast cancer, thus limiting treatment strategies. Attention

has been given to conducting exploratory investigational new drug studies or the so-

called Phase 0 studies.

Successul cancer management varies substantial ly between developing and devel-

oped countries, and one primary challenge is to decrease the signicant gap between

survival rates in developed and developing countries. Early breast cancer detection and

treatment are not readily available in most sub-Saharan Arican countries, or instance,

so women tend to present with late-stage disease and have poor survival rates. I the

care regimen requires multimodality therapeutic or a complex preventive regime, it is

very challenging to provide in a country that lacks appropriate inrastructure and/or

specialized medical sta. Additionally, in the case o breast cancer in young women,the eect o tumor biology and its aggressiveness must be considered. While the United

States is starting to address the impact o breast cancer as the leading cause o death in

younger women, Arican countries have not, and the ravages o this disease continue,

due to poor health conditions and inadequate health care acilities.

In Nigeria, most tumors are diuse, large, and multi-ocal, and radiation therapy is

not readily available. Poor compliance and poor outpatient clinic attendance limit the

ability to assess the ecacy o using hormonal therapy in women whose ER status is

either positive or unknown. While chemotherapy is readily available and used, high

cost limits widespread use. Advanced-stage breast cancer is dicult to manage andresults in a less than 10-15 percent ve-year survival rate. Adjuvant chemotherapy is

the primary treatment method in many developing countries due to the limited avail-

ability o radiation therapy.

Treatment modalities in Ar ica also vary. Data rom one study in Nigeria evaluated

185 subjects who had undergone surgeries spanning mastectomy to modied radical

mastectomy. Neoadjuvant chemotherapy was used in 64 cases, and adjuvant chemo-

therapy was used in 178 cases. Only 70 (33 percent) o the surgery patients returned

or radiotherapy, although all patients were reerred back or radiation by their sur-

geons. All 70 were deemed to have good treatment compliance. Follow-up care varied

rom a mean o 8.4 months; 91 percent died within the rst year o diagnosis, while

89 percent o those lost to ollow-up also died within the rst year ater diagnosis. 63

However, in Nigeria and other Arican countries, breast conserving surgical options

are not readily easible due to late stage presentation, lack o adequate radiotherapy a-

cilities, ew diagnostic oncology specialists, inability to characterize prognostic actors,

young age o patients, and poor ollow-up.

Breast cancer surgery is generally aimed at making a diagnosis, reducing the

tumor burden, controlling disease at a loco-regional level, and obtaining prognostic

inormation. However, in Arica, surgery may soon become an adjuvant orm o

therapy. Adjuvant chemotherapy helps to reduce local recurrence and to increaseoverall survival in women regardless o menopausal or nodal status. Preoperative


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(neoadjuvant) chemotherapy is being used to down stage the tumor and allows or

selection o women with poor prognosis. Neoadjuvant chemotherapy has also been

considered or managing operable cancer and as a prognostic actor; subjects who do

not respond to neoadjuvant therapy will not be given similar drugs post-operatively.

Doxorubicin and Taxane are mainstay combinations that have shown better patho-

logic complete response than other drug regimens. Cisplatin-based regimes seem to

be more eective in ER-negative tumors. The direct treatment cost or early stage

breast cancer in Nigeria is at a minimum is US$800.00 and the cost or advanced

stage disease is much more, neither o which includes the ull economic potential o

the patient or associated cost or care. The gross national product in Nigeria is only

about US$250.00 per person. The rising cost o cancer management makes empha-

sizing prevention a very important management option.Cancer treatment spending in the United States continues to rise, along with total

health care spending. Unexplained cancer-related health disparities remain among

population subgroups, especially AAs and Hispanics. AAs and people with low SES

have the highest rates o both new cancers and cancer deaths. In addition, AAs

and other minorities, poor, and underserved populations are likely to have poorly

controlled co-morbid conditions that impact their response to cancer therapy. Co-

morbid conditions, such as hypertension and diabetes, have accounted or the result-

ing poor survival o up to nearly 50 percent o AAs with breast cancer, as reported

in several studies.64

65

66

67

68


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HealtH systems disparities

summary

The U.S. health system is marred by many cases o neglectand/or ailure to enact and implement health policy mandates that

have the potential to minimize suering and death rom cancer

experienced by Arican Americans and other minorities.

I the United States is to eliminate health disparities, we mustacknowledge that poverty and race/ethnicity do aect health.

Eorts to eliminate breast cancer health disparities must addressthe roles o the health care provider, insurer, and industry, as well as

those o government and academia.

Health disparities can be eliminated by the identication andimplementation o evidence-based, cost-eective, and culturally

appropriate interventions.


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I the United States is to eliminate health disparities, we must acknowledge that

poverty and race/ethnicity do aect health. In certain situations, poverty shouldprobably be considered a carcinogen, although in certain cancer epidemiological stud-

ies, it is dicult to distinguish the impact o poverty rom that o race. Eorts to

eliminate breast cancer health disparities must address the role o providers, insurers,

industry, government, and academia. Obviously, i we are to close the gap in breast

cancer health disparities, the research agenda must use multidisciplinary approaches to

care and address mechanisms or removing all barriers leading to the provision o high

quality eective care to the poor, minorities, and the underserved. Unortunately, the

health system is marred by ar too many cases o neglect and/or ailure to enact and

implement health policy mandates that have the potential to minimize suering anddeath rom cancer experienced by AAs and other minorities.

Data rom the Disease Control Priorities Project-2 (DCPP2) indicated that a num-

ber o inequities remain as a result o disparities in health care services.69 For example,

one-third o the worlds population has no eective access to essential modern medi-

cines or vaccines. Nearly 47 percent o those in sub-Saharan Arica cannot obtain es-

sential drugs when needed. Many barriers prevent people rom obtaining appropriate

breast health care. These barriers can be categorized as the ollowing:

a) Servicestransportation costs; distances to service acilities; hours o operation;

poor quality o care; inappropriate care; cultural and linguistic dierences; and

negative sta attitudes

b) Customerssocial and cultural constraints; lower income or women; burden

o assigned amily roles; limited educational awareness; to a degree, rights and

availability o services; and poor understanding o health inormation provided

c) Providers/Institutionsstigma and discrimination in health settings; lack o

involvement in decision-making process; perception o illness; cultural incom-

petency; bias in provision o recommended screening and treatment guidelines;

health costs; and perceptions

d) Insurerscoverage o eective interventions to improve survival; greater costcontainment concern; and health budgets

HealtH SyStemS DiSParitieS


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The question is how these inequities can best be addressed while maintaining and

advancing previous technological and historic gains in health status. Our challenge is

to identiy specic evidence-based and cost-eective interventions that apply cultur-

ally appropriate, intelligent policy changes that will help us progress toward equitable

health care or all. The application o health policies to support quality health care, re-

duce barriers to access, and generate knowledge in specic prioritized areas o cancer,

specically breast cancer, is critical to eliminating health disparities. Such a program

will likely require additional human and nancial resources.

The DCPP2 report gives special attention to strengthening the health systems. It

indicates that it will be almost impossible to improve health outcomes in a cost-eec-

tive manner unless the health system is better equipped to provide ecient, eective,

and equitable services. Changes to the system would require all components (provid-ers, insurers, and government) to critically analyze business practices and make drastic

changes that will benet all people. A major step in that direction is to make health

a priority and to ocus intensely on prevention. Additionally, recommendations rom

the 2007 ER-negative Think Tank, sponsored by the NCI, urther supported the need

to recognize that ER-negative breast tumors are aggressive. Thereore, it is important

to design studies that will elucidate eective strategies not only or screening, early

detection, prevention, and treatment, but also to assess the biology o these tumors.

Insight into health disparities and the biology o ER-negative breast cancer can be

gained through collaborative studies. Investment priorities should include:

a) Developing evidence-based criteria or identiying breast cancer subtypes;

b) Evaluating research interventions to improve prevention and treatment

outcomes;

c) Identiying biomarkers or young women at high risk or developing aggres-

sive breast cancer;

d) Determining whether dierences in tumor microenvironment and/or nor-

mal tissue contribute to dierences in ER-negative cancer between AA and

NHW women;

e) Ensuring equal access to care;

f) Conducting collaborative studies that collectively analyze available data to

optimize return on past investments;

g) Examining the relationship between SES and ER-negative/basal-like breast

cancer;

h) Developing the inrastructure to support and integrate high-throughput clini-

cal studies on ER-negative and/or triple-negative breast cancers.


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policy implications summary

The most eective approach to solving cancer health disparitiesmust ocus on patients/consumers, health care providers, and the

health delivery system.

In order to begin to minimize health disparities between developedand developing countries, each high-technology approach developed

to address early detection, screening, prevention, and treatment must

have a easible low technological counterpart available.

The top priority in ending cancer health disparities is creatingincentivized prevention measures.

Policies should include legislative requirements to coverscreening, prevention, early detection, and payment coverage byMedicaid, Medicare and other insurers.

Creating a more equal health eld also requires changes outside thehealth sector, within economic, employment, and social policies.


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Policy imPlicationS

cloSinG tHe GaP

Unless we begin to seriously and eectively address cancer prevention and early

screening, cancer incidence will increase rom 10 million to approximately 20million by the year 2020. Estimates suggest that more than 70 percent o all new

cancers cases will occur in people in the developing world and with these new cases,

the mortality rate will increase rom 6 million to more than 12 million each year.

Greater eorts must be made to address and eliminate health disparities in cancer.

Such disparities have persisted and in some cases worsened during the 23 years since

the Heckler report.70 Race as a social construct must be removed rom consideration

in the decisions aecting our public health whether deliberate or subconscious. All

aspects o public healthincluding behavioral and social science, politics, economics,

and medicinemust be embraced in the eort to eliminate health disparities.I we truly value and desire an increase in cancer survivalnot simply longevity,

but high-quality survivalthen we need to adopt a new health system management

approach. Such a program will include education and training or the public and pro-

viders, and will develop a health service delivery system that is accessible to all, with

a special emphasis on those incapable o paying. Perhaps most importantly, it will

create incentivized prevention measures. The most eective approach to solving can-

cer health disparities will ocus on patients/consumers, health care providers, and the

larger health delivery system. In order to begin to minimize health disparities between

developed and developing countries, each high-technology approach developed to ad-

dress early detection, screening, prevention, and treatment must have a easible low

technological counterpart available.

Policy implicationsinclude legislative requirements to cover screening, prevention,

early detection, and payment coverage by Medicaid, Medicare, and other insurers.

Independent eligibility criteria or Medicare should be instituted to reach those with

conditions that could become economically catastrophic. In Arica, insurance and ad-

ditional resources (nancial and human) are needed to improve the provision o high-

quality, multidisciplinary, evidence-based breast health services.

Cost remains a major constraint or many nations, including the United States, so

early detection is an important actor in obtaining eective treatment or alland wil lcontinue to play a major role in the uture. Strategies must be tailored and take into


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barrierS to reDucinG HealtH

DiSParitieS

SolutionS to HealtH

DiSParitieS

1. Poverty and lack o employment 1. Increase employment options

2. Lack o insurance and underinsured 2. Universal insurance coverage

3. Modied clinical trials criteria 3. Increase research opportunities

4. Impact o race construct as variable4. Understand & overcome racial

biases

5. Unequal health service delivery 5. Monitor quality o health systems

6. Co-morbid conditions6. Evaluate relevance o co-

morbidities

7. Detrimental liestyles7. Educate and incentivize healthy

choices

8. Impact o genes and environment8. Evaluate gene/environment

interaction

9. Dierences in tumor biology9. Measure and validate biological

dierences

10. Lack o eective targeted therapies10. Research targeted therapy or

minorities

11. Inability to manipulate the system 11. Provide patient navigators

account the potential or cooperation and synergy between dierent health programs.

Priorities or global cancer prevention need to strike a balance between research, de-

velopment, and implementation.

Another possible approach to initiating the reduction in health disparities and to

creating a more equal health eld would be to make changes outside the health sector,

such as within the economic, employment, and social policies listed below:


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economic impact summary

In 2001, cancer accounted or more than 7 million deaths world-wide (translating into more than 100 million DALYs), with the

majority occurring in developing countries.

Although breast cancer represents 85 percent o the globalcancer disease burden, breast cancer research receives less than our

percent o all available cancer research unding.

Return on research investment can be quite lucrative, butgreater emphasis must be placed on prevention and early detection,

as well as on altering the trend in outcomes or all groups.


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economic imPact

In 2001, cancer accounted or more than 7 million deaths worldwide, with the

majority occurring in developing countries.

public health democracy: u.s. and global health disparities in breast cancer

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