A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change: Closing the Racial Disparity Gap in Breast Cancer

Abstract

It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. CA Cancer J Clin 2015;65: 221-238. © 2015 American Cancer Society.
© 2015 American Cancer Society.

Full text

A Perfect Storm: How Tumor Biology, Genomics,
and Health Care Delivery Patterns Collide to Create a
Racial Survival Disparity in Breast Cancer and
Proposed Interventions for Change
Bobby Daly, MD, MBA
1
; Olufunmilayo I. Olopade, MD, FACP
2
It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women
are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the
factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences
in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor
biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of
treatment for African American patients are of increased significance when these patients are presenting with more aggressive
forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also eval-
uates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than
addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of
future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. CA Can-
cer J Clin 2015;65:221-238. V
C2015 American Cancer Society.
Keywords: breast cancer, disparities research, health services research, precision medicine.
Introduction
According to the American Cancer Society, an estimated 231,840 new cases of female breast cancer will be diagnosed in
2015. These diagnoses represent 29% of all new cancer cases among women. Regrettably, there will also be an estimated
40,290 deaths from breast cancer, which represent 15% of all cancer deaths among women.
1
It is well known that there is a
significant racial divide in breast cancer incidence and mortality rates. White women are more likely to be diagnosed with
breast cancer, but African American women are more likely to die from it. According to National Cancer Institute’s Surveil-
lance, Epidemiology, and End Results (SEER) program, the 2007-2011 age-adjusted incidence rate for breast cancer for
non-Hispanic white women in the United States was 128 per 100,000 women per year compared with 123 for non-His-
panic African American women. However, the mortality rate for non-Hispanic white women was 21.7 per 100,000 per year
compared with 30.6 for non-Hispanic African American women.
2
The overall mortality trend reveals that breast cancer death rates in women have decreased nationally in the United States
since 1990; however, the decreases in death rates began earlier and have been larger in proportionate terms for whites versus
African Americans (Fig. 1).
3,4
SEER data from 1975 to 2011 indicate that white women had a 23% increase in breast cancer
incidence and a 34% decrease in mortality, whereas African American women experienced a 35% increase in incidence and a
2% increase in mortality.
5
Hunt et al
6
examined race-specific breast cancer mortality rates and the corresponding black/
white rate ratios (a rate ratio of 1.00 indicates no disparity between black and white mortality rates) for the largest US cities.
Data were analyzed from 41 cities, and 35 saw an increase in the black/white rate ratio between 1990-1994 and 2005-2009.
The researchers found that the disparity occurred because “white rates improved substantially over the 20-year study period,
while black rates did not.”
6
In addition to Hunt et al,
6
further studies have explored these regional variations in breast cancer mortality by
race (Fig. 2).
7
DeSantis et al
3
analyzed mortality data from the National Center for Health Statistics from 1975 to 2004.
1
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL;
2
Walter L. Palmer Distinguished Service Professor and Director
Center for Clinical Cancer Genetics, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL
Corresponding author: Olufunmilayo I. Olopade, MD, Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Ave-
nue, MC 2115, Chicago, IL 60637; folopade@medicine.bsd.uchicago.edu
DISCLOSURES: Dr. Daly serves on the board of directors for Quadrant Health Care and receives compensation from this entity. Dr. Olopade serves on the
Medical Advisory Board for CancerIQ.
doi: 10.3322/caac.21271. Available online at cacancerjournal.com
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The authors found that trends in breast cancer death rates
varied widely by region. While breast cancer death rates in
white women were decreasing in all 50 states, among Afri-
can American women, breast cancer death rates increased in
2 states, were level in 24 states, and decreased in only 11
states. Many of the states in which African American breast
cancer death rates were level or rising were in the South and
Midwest. This article will review differences in the natural
history, biology, genomics, and patterns of care of breast
cancer in African Americans that may contribute to this dis-
parity in mortality and will review innovative interventions
to close the disparity gap.
Age and Stage
Past reviews of this topic have dwelled on differences in age
and stage at diagnosis between African American and white
women. Indeed, although the overall incidence of breast
cancer is higher in whites, the incidence profile changes
when the data are stratified by age. Among African Ameri-
can women with breast cancer, 33% are diagnosed at an age
less than 50 years, whereas 21.9% of white women are.
8
In
women younger than 35 years, the incidence of breast cancer
in African American women is 1.4 to 2.0 times that in
whites.
9
In addition, African American women do present at
more advanced stages of disease. Using data from the
California Cancer Registry, Kurian et al
10
found that com-
pared with African American patients, white patients had a
higher proportion of tumors that were diagnosed at a local
stage (64.5% vs 54.5%) and that were diagnosed at a size of
2 cm or less (61.7% vs 48.6%). More recently, Iqbal et al
11
conducted an observational study of 373,563 women with
invasive breast cancer from 2004 to 2011 who were identi-
fied in the SEER 18 registries database. In that study,
African American women were less likely to be diagnosed
with stage I breast cancer than non-Hispanic white women
across all age groups (non-Hispanic white women, 50.8%;
African American women, 37.0%). Taking the analysis fur-
ther, Iqbal et al evaluated these small breast tumors and looked
at the percentages of nodal metastases and distant metastases
and the hormone receptor status by race/ethnicity for women
presenting with tumors 2 cm in size. The authors found
that an African American woman with a small-sized breast
tumor was more likely to present with lymph node metastases
(24.1% vs 18.4%), distant metastases (1.5% vs 1.0%), and a
triple-negative tumor (17.2% vs 8.0%) than a non-Hispanic
white woman. African American women were also more likely
to die of breast cancer with small-sized tumors (9.0%) than
non-Hispanic white women (4.6%). Thus, we argue that age
and stage by themselves are not significant but rather gain
importance by how they highlight differences in tumor biol-
ogy, genomics, and patterns of care (Fig. 3).
Tumor Biology: The First Element in the
Perfect Storm (Fig. 4)
Hormone Receptor Status and Human Epidermal
Growth Factor Receptor 2 (HER2)/neu
As stated previously, a factor likely contributing to the
noted differences in age and stage at diagnosis for African
FIGURE 1.Mortality Trends by Race (SEER9, 1968-2008). CMF indicates cyclophosphamide, methotrexate, and fluorouracil; NATO, Nolvadex Adjuvant Trial
Organization. Courtesy of William F. Anderson, MD, MPH, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Closing the Racial Disparity Gap in Breast Cancer
222 CA: A Cancer Journal for Clinicians

American women is differences in tumor biology. Breast
cancer is not a single entity, and breast cancer subtype clas-
sifications are used in the clinical setting to determine prog-
nosis and guide management. The distinct subtypes readily
identified in the clinical setting are based on tumor
markers: estrogen receptor (ER), progesterone receptor
(PR), and HER2/neu amplification. HER2 is a member of
the human epidermal growth factor receptor family and is
encoded on the long arm of chromosome 17; it promotes
cell growth. These heterogeneously diverse tumors have
different disease-specific survival rates. Hormone receptor-
positive tumors benefit from targeted therapies such as selec-
tive ER modulators and aromatase inhibitors. Thus, these
tumors have a more favorable disease-specific survival than
hormone receptor-negative tumors.
14
African American women are more likely to present
with hormone receptor-negative tumors. In an analysis of
the California Cancer Registry, which has collected
information on ER and PR status since 1990, whites had
ahigherproportionoftumorsthatwereluminalincom-
parison with African Americans (71.6% vs 53%), with
luminal tumors defined as ER-positive, PR-positive, or
both and HER2-negative.
10
Even with stratification by
tumor stage, African Americans continue to have a
significantly higher proportion of hormone receptor-
negative tumors than whites for localized and advanced
disease.
15
Evaluating changes in breast cancer incidence
with the reduction of hormone replacement therapy,
Pfeiffer et al
16
employed data from the SEER database
and demonstrated this trend in hormone receptor status:
they found that for non-Hispanic white women aged 50
to 69 years, the incidence of ER-negative tumors declined
4.7% from 2000-2001 to 2003-2004, whereas for African
American women of the same age during the same time
period, ER-negative tumors increased 4.0%.
Although hormone receptor status varies significantly by
race, HER2 status does not show the same divergence.
HER2 amplification or overexpression is present in approxi-
mately 20% of primary invasive breast cancers. HER2-
positive, hormone receptor-negative tumors demonstrate
more aggressive features and worse breast cancer-specific
survival than hormone receptor-positive and HER2-nega-
tive tumors,
14
although survival has vastly improved with
new targeted therapies such as trastuzumab, lapatinib, and
pertuzumab. Unlike the hormone receptor status, the Caro-
lina Breast Cancer Study did not find an association between
the percentage of HER2-positive/ER-negative tumors and
race.
14
In addition, Elledge et al
17
did not find a difference
in HER2 expression between African Americans and whites
in a pathological analysis of more than 6000 tumors. None-
theless, access to appropriate diagnosis and effective HER2
targeted therapies may be limited in resource-poor settings,
leading to worse outcomes for African American women
with HER2-positive breast cancer.
FIGURE 2.Age-Adjusted African American Breast Cancer Mortality for the United States, 2007-2011.
1
Counts are suppressed if fewer than 16 cases
were reported in a specific area-sex-race category. Source: State Cancer Profiles. statecancerprofiles.cancer.gov/map/map.withimage.php?00&
001&055&02&2&02&0&1&6&0#results. Accessed November 21, 2014.
7
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Triple-Negative Breast Cancer
The triple-negative breast cancer subtype lacks the markers
of ER, PR, and HER2 overexpression. The term triple-neg-
ative is often used interchangeably with basal-like breast
cancer because basal-like breast cancers are negative for ER,
PR, and HER2 and overexpress cytokeratins 5 and 6 and
Her1/epidermal growth factor receptor.
14,18
As discussed
previously, although other subtypes have benefited from
drug development regarding hormonal therapies and
HER2-targeted treatments, triple-negative breast cancer
has not experienced the same pharmacologic break-
throughs. As such, even after analyses control for the stage
at diagnosis, women with this subtype have poorer survival
than those with other breast cancers.
19
African American
women have a higher incidence of triple-negative breast
cancer than white women.
20
The Carolina Breast Cancer
Study found that 26% of African American women had
triple-negative breast cancer, whereas 16% of non-African
American women did.
14
This subtype was most common
among premenopausal African American women (39% of
diagnosed cancer subtypes). In Iqbal et al’s study
11
of
373,563 women from the SEER 18 registries database,
17.2% of African American women had triple-negative
breast tumors 2 cm in size, whereas 8.0% of non-Hispanic
white women did. Kurian et al
10
calculated the lifetime risk
of triple-negative breast cancer to be highest in African
American women at 1.98% (1.80%-2.17%) versus 1.25%
(1.20%-1.30%) for non-Hispanic whites and 1.04% (0.96%-
1.13%) for Hispanics. Interestingly, in the Carolina Breast
Cancer Study and the recent analysis of the SEER database by
Iqbal et al., when triple-negative breast cancer patients were
excluded from the analysis, breast cancer-specific survival
remained significantly worse among premenopausal African
American women.
14
Accordingly, this argues that although
the increased incidence of triple-negative breast cancer in
part explains the poor outcomes, factors associated with the
effective treatment of different subtypes of breast cancer
could also in part explain the disparity seen in mortality for
African American and white women.
Histologic Grade
Histologic grade is another characteristic of tumor biology
used to identify more aggressive breast tumors. Schwartz
et al
21
showed that for each combination of tumor size and
lymph nodes, a categorical increase in histologic grade was
associated with a progressive decrease in 10-year survival.
Using data from the SEER program, Henson et al
22
inves-
tigated histologic grade as it relates to the stage of disease,
tumor size, and survival between African American and
white women. The researchers found that regardless of age,
African American women had “proportionately more
Grade III tumors and fewer Grade I and Grade II tumors
for all stages combined and for each individual stage
group.”
22
In addition, for every tumor size, except for
tumors smaller than 1.0 cm, African American women had
significantly more grade 3 tumors than white women.
Relatedly, other studies have demonstrated that African
American women more frequently have tumors that present
with necrosis, which also portends a worse prognosis.
23
Thus, the research has demonstrated that tumor biology is
different in many African American and white patients,
and it must be assessed as a potentially significant contrib-
uting factor to the survival disparity.
Genomics
Germline Mutations: BRCA1 and BRCA2 Mutations
In addition to tumor biology, cancer genomics have become
increasingly important in guiding cancer prognosis and
treatment. Approximately 5% to 10% of breast cancer cases
present in individuals with inherited mutations in autoso-
mal dominant, highly penetrant breast cancer susceptibility
genes.
24
Accounting for 80% to 90% of families containing
FIGURE 3.(A) Breast Cancer Stage Distribution by Race: 2002-2011.
Source: Surveillance, Epidemiology, and End Results Program. Fast stats:
breast; 2014. seer.cancer.gov/faststats/selections.php?#Output. Accessed
August 6, 2014.
12
(B) Breast Cancer Distribution by Receptor Status and
Race: 2010. HER2 indicates human epidermal growth factor receptor 2;
HR, hormone receptor; TNBC, triple-negative breast cancer. Source: Demo-
graphic and clinical characteristics of breast cancer subtypes in women
with invasive breast cancer, SEER-18, excluding Alaska, 2010.
13
Source:
Howlander N, Altekruse SF, Li Cl, et al. US incidence of breast cancer sub-
types defined by joint hormone receptor and HER2 status. J Natl Cancer
Inst. 2014;106:dju055.
14
Closing the Racial Disparity Gap in Breast Cancer
224 CA: A Cancer Journal for Clinicians

multiple cases of breast and ovarian cancer, BRCA1 and
BRCA2 germline mutations are the most common of the
breast cancer susceptibility genes.
25
The profile of these
patients is often the younger patient with a higher grade
tumor that is hormone receptor-negative, which, as dis-
cussed previously, also often matches the profile of the
African American breast cancer patient.
26
Despite similarities between BRCA1-associated breast can-
cers and breast cancer in African Americans, genetic abnor-
malities in African American breast cancer patients remain
underresearched. In one study, Nanda et al
27
performed a
comparative analysis of genetic testing in an ethnically diverse
cohort of high-risk women. The researchers found that
BRCA1 and BRCA2 mutations occur with appreciable
FIGURE 4.The Perfect Storm: The Racial Survival Disparity in Breast Cancer and Interventions for Change. (A) The first element in the storm: tumor
biology and genomics. (B) The second element in the storm: patterns of care. RDI indicates relative dose intensity.
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frequency in high-risk families of African ancestry, with 28%
testing positive for a deleterious mutation in one of these
genes. This frequency, however, was at a lower rate than that
found in non-Hispanic, non-Jewish whites, who had a rate of
46%, because African Americans had a higher rate of poly-
morphisms and variants of unknown significance (44% vs
12% for non-Hispanic, non-Jewish whites). As genomics test-
ing for multiple genes becomes widely adopted, determining
the significance of unclassified variants in minority popula-
tions in breast cancer etiology remains an area for further
research.
27
African Americans are not a monolithic group,
and the results of any one study can never be extrapolated to
the general population of African Americans or blacks of Afri-
can or Caribbean ancestry in the United States. Nonetheless,
high frequencies of mutations in BRCA1 and BRCA2 have
been reported in unselected breast cancer patients of African
ancestry from Nigeria and the Bahamas, and this could inform
population-specific approaches to screening.
28,29
In a
population-based study from the Northern California site of
the Breast Cancer Family Registry, the BRCA1 mutation
prevalence was 16.7% in African American cases diagnosed
under the age of 35 years versus 7.2% in non-Hispanic, non-
Ashkenazi Jewish whites in the same age category.
30
In a
recent report on a large cohort of self-reported African Amer-
ican patients from a single urban institution that integrated
mutation results from next-generation sequencing, clinical
characteristics of the patients, and tumor phenotype, Churpek
et al
31
showed that inherited mutations in the BRCA1 and
BRCA2 genes were the strongest predictors of breast and/or
ovarian cancer risk. In that study, 68 damaging germline
mutations were identified in 65 of 289 African American
patients tested (22%; 95% confidence interval [CI], 18%-
28%). They found that 10.0% (29 of 289) of cases carried
pathogenic BRCA1 mutations, and 8.0% (23 of 289) of cases
were BRCA2 mutation-positive. A much smaller fraction car-
ried mutations in PALB2,CHEK2,BARD1,ATM,PTEN,or
TP53. More than 2 decades after the BRCA1 and BRCA2
genes were identified, larger studies using next-generation
sequencing in diverse populations are still needed to derive
true estimates of the burden of mutations in both genes in
underserved and understudied populations.
Somatic Mutations: TP53 Mutations
In addition to germline BRCA mutations, somatic muta-
tions are also known to contribute to breast cancer out-
comes. Germline mutations in TP53 account for less than
1% of female breast cancers, but somatic mutations are
found in approximately 50% of breast cancers and are asso-
ciated with a worse prognosis.
32
In fact, Dookeran et al
33
demonstrated that TP53 is an independent predictor of sur-
vival after adjustments for the effects of age, stage, grade,
and subtype. Although TP53 mutations have been found to
occur with equal frequency in whites and African Ameri-
cans,
17
several studies have found differences in the specific
gene alterations.
34,35
These genetic variants have been
demonstrated to have potentially different impacts on
survival. Shiao et al
34
found a significant increase in mortal-
ity in African American patients with p53 mutations that
was not observed in white patients. Accordingly, the spe-
cific gene alterations found in African American and white
patients could have a differential effect on breast cancer
behavior, but this has not been explored with sufficient
rigor. The Cancer Genome Atlas and the International
Cancer Genome Atlas are large collaborative projects that
should specifically recruit biospecimens and oversample
breast tumors from women of African ancestry to address
differences in the spectrum of clinically relevant germline
and somatic gene mutations.
36,37
Epigenetics and Metabolomics: RASSF1A,BRCA1,
and MYC Activation Signature
Epigenetics is another focus of genomics and metabolomics
research that could potentially be significant in explaining
the survival disparity. In a meta-analysis, promoter hyper-
methylation of the tumor suppressor gene RAS-association
domain family 1 isoform A (RASSF1A) conferred a higher
risk of relapse and worse survival in patients with breast
cancer.
38
A study that compared molecular alterations at
the epigenetic level found that African American women,
less than 50 years of age, with hormone receptor-negative
tumors have a significantly higher frequency of hypermeth-
ylation of RASSF1A than white women.
39
BRCA1 methyl-
ation has also been shown to play a role in a significant
proportion of triple-negative breast cancers and is a plausi-
ble biological mechanism for breast cancer disparities.
40
At
its promoter, BRCA1 transcription is controlled by several
mediators of metabolic transduction, including histone ace-
tyltransferases, p300, and P300/CBP-associated factor,
which play distinct roles in upregulating BRCA1 transcrip-
tion through histone acetylation.
41
This activity is opposed
by the action of nicotinamide adenine dinucleotide
(NADH) through the NADH-activated C-terminal–bind-
ing protein (CtBP) complexes.
42
Gardner and his col-
leagues have shown that CtBP serves as a direct molecular
link between BRCA1 expression and the metabolic status of
the cells, where metabolic manipulation of NADH levels,
through alterations of glycolysis or hypoxia, could directly
influence the transcription of the BRCA1 gene. This thus
provides molecular evidence of a link between conditions of
metabolic imbalance such as obesity and diabetes, which is
highly prevalent among African Americans and breast can-
cer.
42
Terunuma et al
43
also recently showed that African
American breast cancer patients develop a breast tumor
with an MYC activation signature more commonly than
Closing the Racial Disparity Gap in Breast Cancer
226 CA: A Cancer Journal for Clinicians

European-American patients, and this signature occurs
mostly in ER-negative tumors. The occurence of this sig-
nature can be partly explained by single nucleotide variants
(SNPs) at the 8q24 genomic locus, which has been linked
to a higher risk of prostate cancer in African American
men.
44
Patients with the 8q24 variant, which encodes a
transcription factor 4 binding site, are more likely to have
an MYC activation signature in their tumors. Thus, in part,
the heightened occurrence of the MYC signature in African
American patients compared to white patients seems to be
linked to ancestry, which affects metabolism and breast
cancer biology. Interestingly, the tumor metabolome of
ER-negative breast tumors with the MYC activation signa-
ture is very different from that of ER-negative tumors
without this signature. This again underscores the hetero-
geneity between the biology of African American and white
breast cancer tumors.
Cancer Risk Clinics: Patterns of Referral
These genetic variations in African Americans, with their
associated aggressive breast cancer characteristics, highlight
the need for further study of breast cancer genomics in
minority populations. However, Armstrong et al
45
illumi-
nated the existence of racial/ethnic disparities in patterns
of referral to cancer risk clinics. In their study, African
American women with a family history of breast or ovarian
cancer were significantly less likely to undergo genetic
counseling for BRCA1/2 testing than white women with
this family history (odds ratio [OR], 0.22; 95% CI, 0.12-
0.40). The results of this study were significant for the
magnitude of the disparity, with white women having an
almost 5 times greater odds of undergoing this clinically
important evaluation.
45
It has also been demonstrated that
there is a lack of education in the African American com-
munity by physicians about the role and importance of can-
cer genomics and genetic counseling.
46
In focus group
sessions, Matthews et al
47
found that among a sample of
African American participants with a strong family history
of cancer, nearly one-half (48%) reported rarely discussing
cancer-related issues with family members, and none had
knowledge of breast cancer genomics, genetic counseling,
or the BRCA genes. Wideroff et al
48
have reported that
the factor most strongly associated with physician use of
genetic services, more so than availability of services, is
patient inquiry about whether she or he can or should get
tested (OR, 5.52; 95% CI, 3.97-7.67).
48
These differences
in patterns of referral contribute to the paucity of data on
African American genetic variants in BRCA1 and BRCA2
susceptibility genes and the potential misclassification of
deleterious mutations as unclassified variants.
Although these differences in tumor biology and
genomics tell part of the mortality disparity story, they are
not the only voices, and there is more of the story to be
told. In a study of African American and white patients in
South Carolina, Adams et al
49
determined survival rates by
ethnicity adjusted for disease stage and other prognostic
characteristics. After they controlled for age, stage, ER, and
HER2 as well as insurance status, African American
women still had a 2-fold excess risk of death from breast
cancer (hazard ratio [HR], 2.41; 95% CI, 1.21-4.79).
Henson et al
22
demonstrated that for each combination of
grade and stage, the 6-year disease-specific survival rate was
consistently lower for African American women versus
white women, and Menashe et al
50
showed that the hazard
of breast cancer death was statistically significantly higher
in African American women versus white women, regard-
less of ER expression, and it persisted after adjustments for
multiple tumor and demographic characteristics. Finally, in
another study that examined survival after controlling for
stage and hormone receptor status, the authors found that
African American women younger than 50 years had sig-
nificantly lower stage-specific survival rates for ER-positive
and ER-negative tumors.
51
Thus, in addition to differences
in the innate characteristics of the breast tumors, racial dif-
ferences in patterns of care for women with breast cancer
must be considered in unraveling the observed disparity in
mortality.
Patterns of Care: The Second Element of the
Perfect Storm
Screening and Treatment
Mammography
Despite advances in breast cancer imaging technology, the
mainstay of breast cancer screening has remained mammog-
raphy. Chu et al
51
found that African American females
have less early-stage disease in every age group for each
hormone receptor status, and this raises the concern that
mammography screening might be inadequate in this popu-
lation. Although historically African American women used
mammography less than white women, this difference has
fortunately almost disappeared with time.
4
According to
results from the 2010 National Health Interview Survey,
among women who were 40 years or older, 50.6% of non-
Hispanic African Americans and 51.5% of non-Hispanic
whites reported having a mammogram within the past
year.
52
A study by van Ravesteyn et al
53
designed to further
investigate how much of the mortality disparity could be
attributed to racial differences in factors such as uptake in
mammography demonstrated that the effect of reduced
screening use on breast cancer mortality rates was relatively
small (7%-8%).
However, although mammography uptake may be simi-
lar, there remain differences in the quality and follow-up
of abnormal imaging results. A study of mammography
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capacity and quality in a large urban setting found that the
facilities that served predominantly minority women were
less likely to be academic (27% vs 71%) or private institu-
tions (29% vs 43%), less likely to have digital mammog-
raphy (18% vs 71%), and less likely to have dedicated breast
imaging specialists reading the films (23% vs 87%). The
authors concluded that the mammography process was bro-
ken, with quality differences in the manner in which the
centers provided care and reported back results.
54
High-
lighting the importance of place on breast cancer care,
Gehlert at al.
55
asserted that ensuring that inner-city health
facilities have up-to-date, well-maintained equipment and
that mammographers have access to continuing training
and opportunities for consultation should help reduce
African American breast cancer mortality.
With respect to follow-up of abnormal imaging results, a
large retrospective cohort study of 6722 women with an
abnormal mammogram from January 2002 through
December 2002 at a New York academic medical center
found longer times to diagnostic follow-up for African
American versus white women. The median number of
days to diagnostic follow-up after an abnormal mammo-
gram was 20 days for African American patients and 21
days for Hispanic patients versus 14 days for white patients,
and racial disparities remained significant after the
researchers controlled for age, Breast Imaging Reporting
and Data System (BIRADS) category, insurance status,
provider practice location, and median household income.
More importantly, in the population of women with a BIR-
ADS classification of 4 or 5 who did not have same-day
additional imaging, the median number of days to follow-
up was 26 for African American women and 23 days for
Hispanic women versus 14 days for white women
(P<.05).
56
Delays in Treatment
A cascade of delays has been documented in breast cancer
care for African American women in addition to the delays
just discussed regarding abnormal mammogram follow-up.
Silber et al
57
recently investigated factors associated with
differences in African American and white breast cancer
outcomes in a large population-based study using SEER-
Medicare data. The mean time from diagnosis to treatment
was 29.2 days for African Americans versus 22.5 days for
whites (P<.001). The authors also found that African
Americans were more likely to have very long treatment
delays. Six percent of African Americans did not initiate
treatment within the first 3 months of the diagnosis,
whereas only 3% of whites did not (P<.001). Gwyn et al
58
also found potentially clinically significant treatment delays
more often for African American women versus white
women. The time from medical consultation to the initia-
tion of treatment was greater than 3 months for 22.4% of
African American women versus 14.3% of white women.
Three months was chosen as clinically significant because
Richards et al
59
demonstrated that a delay greater than or
equal to 3 months may affect survival. The impact of treat-
ment delays on survival was also explored by McLaughlin
et al
60
in a study of North Carolina Medicaid enrollees
diagnosed with breast cancer. A large proportion of this
population (44.3%) were racial minorities. The authors
found that 1 in 10 women waited 60 days to initiate treat-
ment after a diagnosis of breast cancer, and a delay of this
length among patients with late-stage breast cancer was
associated with 66% and 88% increased risks of overall and
breast cancer-related death, respectively. Thus, delays in
the diagnosis and treatment of African American women
are eroding factors that worsen the survival gap.
Misuse of Treatment
Once treatment is initiated, studies have demonstrated that
African Americans are often receiving inappropriate ther-
apy. Li et al
61
examined SEER data from 1992 to 1998 to
evaluate the relationship between race and ethnicity and
breast cancer treatment. African American women with
stage I or II disease were 40% more likely to receive inap-
propriate treatment (P<.05), which was defined as not
meeting 2000 National Comprehensive Cancer Network
practice guidelines. In another study, a prospective analysis
of 957 patients in 101 oncology practices, Griggs et al
62
found more frequent use of non–guideline-concordant
adjuvant chemotherapy regimens in African American
women. In a univariate analysis, African American patients
were more likely to receive a nonstandard regimen than
whites (19% vs 11%, P5.047). Although we will discuss
further in this review whether guidelines based on clinical
trials are appropriate for African American patients, the
studies demonstrate that these women are not uniformly
receiving standard-of-care treatment.
Underuse of Treatment
Aside from the misuse of treatment, studies have also
examined undertreatment of African American patients
with breast cancer. Freedman et al
63
examined racial dis-
parities in local therapy for early-stage breast cancer. For
women with stage I and II breast cancers, guidelines rec-
ommend breast-conserving surgery with whole breast radi-
ation or modified radical mastectomy for definitive local
therapy. The authors found lower rates of definitive local
therapy for African American patients versus white patients
(86.0% vs 82.8%, P<.0001).
Beyond local treatment, another study examined chemo-
therapy administration among African American patients
with stage I to III breast cancer at 10 different treatment
sites. African American patients received a lower dose pro-
portion (actual vs expected dose) and relative dose intensity
Closing the Racial Disparity Gap in Breast Cancer
228 CA: A Cancer Journal for Clinicians

than white patients (0.80 vs 0.85 [P5.03] and 0.76 vs 0.80
[P5.01]). The authors found that differences in biological
and medical characteristics, such as tolerance of therapy,
comorbidity, and leukocyte counts, did not explain the dif-
ference. In fact, despite the association between lower leu-
kocyte counts and African American ethnicity, there was
no evidence that the white blood cell level accounted for
the difference in dose proportion or relative dose intensity.
Most significantly, the authors discovered that more
African Americans had chemotherapy dose reductions for
the first cycle of treatment (OR for nonoverweight African
Americans, 3.7; P<.05), and this perhaps indicates physi-
cian assumptions regarding African American patients’
ability to tolerate chemotherapy.
64
Smith et al
65
also examined ethnic differences in the
administration of adjuvant chemotherapy for breast cancer.
The authors found that modification of chemotherapy
administration was more common among African Ameri-
can patients (65.2% vs 41.8%, relative risk, 1.56; P5.04),
and African American patients were also 2.49 times more
likely than white patients to receive reduced cumulative
doses of chemotherapy (P5.03). In contrast to their
hypothesis and similarly to the aforementioned study, they
also did not find excess hematologic toxicity among African
American patients as the source of these chemotherapy
modifications.
Silber et al
57
also examined differences in the administra-
tion of chemotherapy between white and African American
breast cancer patients. The authors found that 3.7% of
African Americans received both an anthracycline and a
taxane, whereas 5.0% of whites matched to African Ameri-
cans at presentation did. Bickell et al
66
explored further
racial disparity in the underuse of adjuvant breast cancer
treatment. The researchers examined the medical records of
677 women treated surgically for stage I or II breast cancer
in 1999 to 2000. The study defined underuse as omissions
of radiotherapy after breast-conserving surgery, adjuvant
chemotherapy after the resection of hormone receptor-
negative tumors 1 cm, or of hormonal therapy for
receptor-positive tumors 1 cm. Underuse of appropriate
adjuvant treatment was found in 34% of African American
patients versus 16% of white patients (P<.001). There
were racial disparities present in all 3 adjuvant therapies
assessed.
Oral hormonal therapy has been demonstrated in clinical
trials to be effective in preventing breast cancer recurrence
and death in women with early-stage breast cancer.
67
Bickell et al’s study
66
documented underuse of this treat-
ment in African American patients. Partridge et al
68
con-
ducted the largest study of the use of oral antineoplastics
outside a clinical trial setting. Their study consisted of 2378
primary breast cancer patients enrolled in New Jersey’s
Medicaid or pharmaceutical assistance program, with the
main outcome being the number of days covered by filled
prescriptions for tamoxifen in the first year of therapy. The
study found that nonwhite patients had significantly lower
adherence rates than white patients (OR, 1.62; 95% CI
1.26-2.09). Although further investigation is needed to
determine the drivers of this nonadherence to oral
antineoplastics in African American patients, the cost of
these medications has been proposed as a significant factor
leading to their underuse. Streeter et al
69
analyzed a nation-
ally representative pharmacy claims database for oral anti-
neoplastics and calculated the abandonment rate for the
initial claim. Not surprisingly, high cost sharing and low
income were associated with a higher abandonment rate
(P<.05). Despite being an important component of health
equity research, treatment adherence has been recently iden-
tified by the Association of American Medical Colleges as a
critically underrepresented area in disparities-focused health
services research; it represents only 4% of health outcomes
assessed in disparities-focused research projects.
70
More
attention to this area is needed to understand the underuse
of hormonal therapies in African American breast cancer
patients.
The treatment strategies that have been shown to be
delayed, underused, or misused in African American
patients in the aforementioned studies have been demon-
strated to improve disease-free and overall survival in large
randomized trials. Furthermore, diminished total dose and
dose intensity of adjuvant chemotherapy for breast cancer
have been associated with lower survival rates.
71,72
Thus,
these quality-of-care failures in breast cancer treatment for
minority patients are thought to partially explain the racial
survival disparity because it has been proposed that African
American and white patients derive a similar benefit from
systemic therapy when it is administered in accordance with
their clinical and pathologic presentation.
73
This assump-
tion, though, becomes more nuanced when the clinical trial
experience is reviewed.
Clinical Trial Experience
Dignam
73
examined survival by race in several National
Surgical Adjuvant Breast and Bowel Project trials. He
found that the benefit from systemic adjuvant therapy for
recurrence and mortality reduction was comparable between
African American and white patients. His survey of trials
consistently indicated equivalent disease-free survival.
However, a mortality deficit for African Americans was also
consistently found. There was a 21% excess risk of mortality
among lymph node-negative African American patients and
a 17% excess risk of mortality among lymph node-positive
African American patients. This excess mortality risk was
thought to be attributable to greater mortality from non-
cancer causes among African American patients rather than
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a failure of African American patients to respond to breast
cancer treatment.
In contrast to Dignam’s findings,
73
Hershman et al
74
assessed the association between race and treatment discon-
tinuation/delay, white blood cell counts, and survival in
women enrolled in Southwest Oncology Group adjuvant
breast cancer trials. The study found that African American
women were significantly more likely to experience treat-
ment discontinuation/delay than white women (87% vs
81%, respectively, P5.04). These delays were not accounted
for by toxicities because these were experienced in similar
proportions by race. African American women were also
more likely to miss appointments than white women (19%
vs 9%, P5.0002); perhaps, as Hassett and Griggs
75
specu-
lated, this speaks to economic barriers, including the inabil-
ity to arrange alternate child care, miss work, or afford
transportation to the clinic. However, despite these barriers
to care for African American patients, they still received the
same mean relative dose intensity as white patients (87% for
African Americans vs 86% for whites).
In their survival analysis, Hershman et al
74
controlled for
treatment-related factors such as dose reductions and delays,
body surface area, baseline white blood counts, and other
predictors of survival and still found that African American
women had worse disease-free (HR, 1.56; 95% CI, 1.15-
2.11) and overall survival (HR, 1.95; 95% CI, 1.36-2.78)
than white women. The authors concluded that the study
was “unable to demonstrate that any factor related to treat-
ment quality or delivery contributed to racial differences in
survival between the groups.”
74
The study thus established 2
important findings related to the disparity gap. First, even in
the controlled setting of a clinical trial, African American
patients faced barriers to optimal treatment,
75
and, second,
despite attempts to control for treatment quality and deliv-
ery, African American women still had worse outcomes.
Role of Comorbidity and Obesity
Beyond tumor, diagnostic, and treatment factors, research-
ers have argued that other clinical factors, including obesity
and associated comorbidities, are the significant contribut-
ing factors to the racial mortality disparity. Using a histori-
cal cohort from the Henry Ford Health System,
Tammemagi et al
76
evaluated the role of comorbidity in
racial disparity among breast cancer survivors. The research-
ers found that at least one adverse comorbidity was observed
in 86% of African Americans versus 65.7% of whites (OR,
3.20; 95% CI, 2.17-4.72), and comorbidity explained nearly
half of the overall survival disparity. Diabetes and hyperten-
sion were particularly significant in explaining the disparity.
Tammemagi et al
76
also found a preponderance of obesity
among African American patients. A body mass index of
25 kg/m
2
or higher (classified as overweight) was observed in
72% of African Americans versus 49.7% of whites (P<.001).
Ogden et al
77
also demonstrated that the prevalence of obesity
dropped 13.2% among non-Hispanic white women 60 years
old or older from 1999-2000 to 2003-2004 but increased
7.6% among African American women in the same age group
during the same time period. Obesity has been proposed to
affect breast cancer survival through a variety of mechanisms,
including mammography use, screening performance, mam-
mography follow-up, and treatment efficacy.
78–80
Despite these findings, studies controlling for comorbid-
ities and obesity have still found a racial survival difference.
Griggs et al
62
found that comorbidity was not associated
with receiving nonstandard treatment. In addition, as
discussed previously, the survival difference remains in clini-
cal trials, which would presumably control for significant
clinical comorbidities,
20
and a survival disparity was found
despite researchers’ controlling for body surface area in
Hershman et al’s study
74
examining data from Southwest
Oncology Group trials. Finally, Curtis et al
81
examined
SEER-Medicare data to evaluate racial differences in breast
cancer survival after adjustments for several factors, including
comorbidity. Comorbidity contributed relatively little to the
racial differences noted (approximately 2% in their model).
Thus, the search for the source of the breast cancer racial
survival disparity has identified multiple contributing
agents. We have reviewed the fact that tumor biology and
genomics are significantly different between African Amer-
ican and white patients. We have also discussed that there
are differences in screening, follow-up, and treatment by
race, with African American patients receiving inferior
quality of care. However, the consensus from the research
is that neither of these features alone is sufficient to explain
the breast cancer survival gap. The conclusion to be drawn
is that in closing this gap, policymakers must consider both
the biological differences and the patterns-of-care differen-
ces concurrently to form effective interventions.
Interventions
Insurance
Eliminating racial disparities in cancer mortality through
effective interventions has become an increasingly important
imperative in federal, state, and community health
care programs. It is one of the American Cancer Society’s
2015 challenge goals and of the American Society of Clinical
Oncology.
4,82
It has been posited that interventions aimed at
providing insurance coverage to minority patients will be
able to reduce racial health care disparities.
83
Studies have
indicated that women without insurance present with more
advanced-stage disease,
84,85
are more likely to not undergo
breast-conserving surgery for nonmetastatic T1/T2
tumors,
85
and are more likely to receive nonstandard
treatment.
86
However, outside of cancer care, a large study
of Medicaid expansion in Oregon demonstrated that
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230 CA: A Cancer Journal for Clinicians

Medicaid coverage alone generated no significant improve-
ments in measured physical health outcomes in the first 2
years.
87
Thus, coverage alone does not ensure that patients
will be able to navigate the health care system and that qual-
ity care will be provided.
In breast cancer, Hoffman et al
88
evaluated the effect of
race and health insurance on the diagnostic time, which
was defined as the number of days from a suspicious finding
to diagnostic resolution (either no evidence of malignancy
on diagnostic mammogram or definitive diagnosis by
biopsy), in a large urban setting. The authors’ hypothesis
was that every insured patient would receive the same
timely diagnosis as any other patient with equivalent insur-
ance, regardless of race or ethnicity. The study found that
non-Hispanic whites with government insurance had sig-
nificantly shorter diagnostic times than non-Hispanic Afri-
can Americans with government insurance (P5.0003): the
average diagnostic times were 12 and 39 days, respectively.
In addition, privately insured non-Hispanic whites also had
significantly shorter diagnostic times than privately insured
non-Hispanic African Americans (16 versus 27 days). The
odds of non-Hispanic African Americans having diagnostic
delays greater than 60 days (ie, past the guideline recom-
mended by the Centers for Disease Control and Preven-
tion) were 1.6 times greater than the odds for non-
Hispanic whites. The authors concluded that the lack of
health insurance is not the only barrier to quality care for
African American patients.
This study supports the findings discussed earlier by
Press et al,
56
who examined median days to follow-up
after an abnormal mammogram. Their study found that
differences remained significant in their multivariate
model after they controlled for insurance. In addition,
Short et al
89
demonstrated that when the health plan sta-
tus was held constant in a retrospective study of 476 white
patients and 99 African American patients with newly
diagnosed breast cancer, African Americans had a higher
mortality rate (8.1% vs 3.6%, P5.06) and were diagnosed
at a later stage (OR, 1.71; P5.02). Accordingly, interven-
tions must go beyond just providing health insurance to
minorities in order to have a significant impact on the
mortality gap.
Patient Education and Physician Communication
An underlying cause frequently cited for the delayed diagno-
sis and treatment of African American patients with breast
cancer is a lack of patient education and physician communi-
cation. These elements are essential components of quality
care. In a qualitative study of low-income, ethnically diverse
women older than 40 years, Allen et al
90
identified salient
themes differentiating women who received timely follow-
up from those who did not. For the women who delayed
follow-up, prominent themes were dissatisfaction with the
communication of results, disrespect on the part of providers
and clinic staff, logistical barriers to accessing services, anxi-
ety and fear about a possible cancer diagnosis, and a lack of
information about breast cancer screening and symptoms. In
another study, Masi and Gehlert
91
employed focus group
interviews of African American adults to characterize per-
ceptions of breast cancer treatment. Their analysis revealed a
core set of themes, including mistrust of the medical estab-
lishment and concern about the effect of racism on treatment
quality; they concluded that “in the eyes of many study
participants, the issues of trust, race, and quality of care
were closely intertwined.”
91
With interventions aimed at
improving patient education and physician communication,
these barriers identified by Allen et al and Masi and Gehlert
can likely be overcome, and this will allow more timely diag-
nosis and treatment.
Janz et al
92
examined racial differences in the adequacy
of information and support for women with breast cancer.
The researchers used survey data from a population of 1766
women diagnosed with nonmetastatic breast cancer and
reported to the Los Angeles County SEER registry. The
study found that across treatment- and survivorship-related
issues, African American women desired more information
than white women (P<.001). One of the explanations for
the unmet information needs posited by the authors is a
failure to provide culturally appropriate information related
to health issues. This breakdown in patient education and
communication was demonstrated by Hawley et al
93
to
hold across providers and locations.
Hawley et al
93
evaluated the association between minor-
ity patients’ knowledge of breast cancer treatment risks and
benefits and provider characteristics and treatment loca-
tions. The provider characteristics included surgeon-level
independent variables, such as breast cancer procedure vol-
ume and demographics (years in practice and sex). The
treatment location variable was categorized into 1 of 3
groups: National Cancer Institute-designated cancer center,
American College of Surgeons cancer program, or no spe-
cific cancer program. Provider characteristics and treatment
location are factors previously identified to be associated
with high-quality care. The study employed a multivariate
regression to identify associations between patient, surgeon,
and treatment setting factors and accurate knowledge of the
survival benefit and recurrence risk related to mastectomy
and breast-conserving surgery with radiation. The authors
found that minority women were significantly less likely to
have adequate survival knowledge and more likely to be
uncertain about recurrence risk than white patients
(P<.001). In the multivariate logistic regression model,
neither provider characteristics nor treatment setting atte-
nuated observed racial disparities in knowledge. Quality
health care depends on the ability to make an informed
treatment decision. Although patient education also plays a
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role, it has been demonstrated that breast cancer death rates
are substantially higher for African American women than
white women with the same education level.
94
As the
authors concluded, this study underscores the need for pro-
viders to communicate information effectively to all
patients, and effective communication relies on the cultural
competency of providers.
95
Without effective, culturally
competent communication, there are treatment delays and
omissions that result in poor quality care. Currently, the
research has established that these communication deficits
are found across provider and treatment center types.
African-born immigrants, one of the fastest growing
immigrant groups in the United States, are a population in
which the lack of culturally competent patient communica-
tion has been especially evident. In a systematic literature
review of cancer care among African immigrants, Hurtado-de-
Mendoza et al
96
found that African immigrants have limited
knowledge about cancer care, associate breast cancer with
certain death, and sometimes attribute breast cancer to a
punishment from God. These perceptions create barriers to
screening and treatment because these patients have limited
knowledge and awareness about screening practices, have
emotions at odds with screening (shame, modesty, and fear
of screening procedures), and have cultural values perceived
to be at odds with medical practices.
96
Interventions that
have been shown to be successful with immigrant breast can-
cer health are those that employ linguistically and culturally
tailored programs.
97
This was demonstrated by Percac-Lima
et al
98
in a study in which immigrant patients were educated
on breast health and breast cancer detection with a linguisti-
cally and culturally tailored breast cancer screening program.
During the 4-year study period, the adjusted mammography
rates for refugee women in the program climbed from 64.1%
(vs an English-speaking rate of 76.5% and a Spanish-
speaking rate of 85.2%) to 81.2% at the end of the program.
Patient Navigation
Patient navigation has been championed as a method of
improving care in breast cancer by enhancing patient com-
munication and education and removing barriers to timely
care. Patient navigation empowers patients to become
knowledgeable about their own health and supports patients
through the course of care.
99
Patient navigation programs
have been developed to address the patient communication
breakdowns and the underuse and misuse of treatment
among vulnerable populations that have already been
detailed in this review and are thought to be contributing to
the racial mortality gap.
100
A benefit of patient navigation has been suggested in stud-
ies evaluating the time to diagnosis and follow-up from an
abnormal screening. Markossian et al
101
evaluated the effi-
cacy of a Chicago-based cancer patient navigation program
developed to reduce the time from abnormal screening to
definitive diagnostic testing. The majority of patients in this
study were Hispanic (66%) and African American (32%).
Compared with controls without navigation, the breast navi-
gation group had a shorter time to diagnostic resolution
(adjusted HR, 1.65; 95% CI, 1.20-2.28; P5.002). Hoffman
et al
102
evaluated patient navigation in the District of
Columbia to determine its ability to reduce the breast cancer
diagnostic time (the number of days from abnormal screen-
ing to a definitive diagnosis). African American women
composed 48% of the study population. They found that
navigated women reached their diagnostic resolution
significantly faster than nonnavigated women, and there
was a nearly 4-fold reduction in the time to diagnostic
resolution for navigated women versus nonnavigated
women who resolved with cancer. Finally, another study of
urban minority women examined delays in follow-up after
an abnormal mammogram by randomly assigning patients
to usual care or usual care plus patient navigation.
103
Women in the intervention group had shorter times to
diagnostic resolution (mean, 25 versus 42.7 days; P5.001)
and also had lower mean anxiety scores and higher mean
satisfaction scores.
In a national multicenter study, Ko et al
99
were the first
to evaluate whether patient navigation can improve the
quality of breast cancer care. The authors hypothesized that
breast cancer patients assigned a navigator would be more
likely to receive recommended standard treatment than
patients without a navigator. Three separate quality meas-
ures of breast cancer care, including initiation of anti-
estrogen therapy, radiation therapy, and chemotherapy,
were evaluated. The participants in the study were racially and
ethnically diverse, with a plurality being African American
(37.5%). The study produced mixed results: navigated patients
had a statistically significant higher likelihood of receiving
anti-estrogen therapy than nonnavigated controls (OR, 1.73;
P5.004), but navigated patients eligible for radiation therapy
were no more likely to receive radiation (OR, 1.42;
P5.22) than controls. The initiation of chemotherapy
could not be accurately assessed because of a limited sample
size. The study concluded that navigation alone does not
remove all of the barriers to quality care for breast cancer
patients, and barriers are diverse and potentially specific to
the treatment modality.
A study by Tejeda et al
104
used a systematic framework
to characterize the barriers faced by minority patients with
breast and cervical cancer. They categorized barriers as
intrapersonal (defined as characteristics of the individual;
eg, knowledge, belief, attitudes, and transportation and
financial barriers), interpersonal (processes that involve
other people; eg, social support system, child care, and
employment issues), and institutional (characteristics and
policies of organizations). The authors found that although
navigators were able to easily resolve intrapersonal-level
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232 CA: A Cancer Journal for Clinicians

barriers, ongoing navigation was needed to address
institutional-level barriers. Thus, patient navigation in a
vacuum does not work, and it is only in examining the
entire health care system that changes can be implemented
to eliminate barriers to quality care and close the racial
mortality chasm.
System Change
To this effect, Clarke et al
105
performed a systematic review
of the disparities intervention literature to understand
which interventions are being evaluated to improve minor-
ity health. The authors found that the majority of dispar-
ities interventions are focused on changing the patient
rather than the system that serves her, with the most com-
mon strategy to improve minority health being education
and training (37% of strategies studied). Interventions
aimed at health care system improvements were surpris-
ingly few, with the responsibility for change resting with
the patient rather than the care delivery system. Interven-
tions incorporating community involvement were also
severely lacking and reflected only 6.5% of the reviewed
intervention tactics. The role of place or the community
where care is delivered is hard to underestimate because it
affects access to and quality of care; therefore, interventions
need to be owned by the community to be sustained
through time.
55
The majority of interventions failed to
involve major stakeholders, including providers, health care
institutions, community organizers, and policy makers, and
accordingly were unlikely to succeed in creating meaningful
change.
In breast cancer, there have been examples of successful
system-based approaches to reducing the racial mortality
disparity. At New York area hospitals, Bickell et al
106
implemented a tracking and feedback registry to close the
referral loop between surgeons and oncologists to decrease
the underuse of valuable adjuvant treatments. The inter-
vention targeted important quality issues in both communi-
cation (the breakdown in dialogue among providers of
different specialties and between providers and patients)
and the underuse of adjuvant treatment in minorities. The
intervention was designed to address failures in the health
care system through the involvement of leadership from
pathology, surgery, and oncology. The intervention also
incorporated technology, with the tracking software
prompting contact with patients who had failed to follow
up. Among African American and Hispanic women, there
were statistically significant decreases in the underuse of
radiotherapy (23% before the intervention vs 10% after the
intervention, P5.02), chemotherapy (26% before the
intervention vs 6% after the intervention, P5.01), and
hormonal therapy (27% before the intervention vs 11%
after the intervention, P5.01). After the intervention,
minority race was no longer a risk factor for low rates of
oncology consultation (adjusted relative risk, 1.0; 95% CI,
0.7-1.3) or for underuse of adjuvant therapy (adjusted rela-
tive risk, 1.0; 95% CI, 0.8-1.3).
106
Interestingly, 4 of the 6
hospitals involved in this study had a patient navigation
system in place; however, as discussed, just the navigation
system alone was not enough to address the system failures
leading to the disparities in care.
Ansell et al
54
also described a system-based approach to
reducing the breast cancer mortality disparity in Chicago.
The Metropolitan Chicago Breast Cancer Taskforce was
composed of 102 individuals and 74 Chicago area organiza-
tions to address the growing African American/white
breast cancer mortality disparity. The taskforce identified a
number of themes underlying the disparity gap, including a
need for breast cancer education and outreach programs for
African American women, a broken mammography process
leading to quality differences between African American and
white patients, and a number of barriers to diagnosis and
treatment, including fear, a lack of primary care, the burden
of insurance copays/deductibles, and the noncompletion of
treatment for social and economic reasons. After identifying
these underlying causes, the taskforce proposed that
addressing one aspect of the health care system would not
correct the problem, but rather quality improvement initia-
tives would have to occur across the continuum of care for
breast cancer.
In Delaware, such a broad system-based intervention was
implemented to eliminate health disparities in colorectal
cancer.
107
Delaware created a comprehensive statewide colo-
rectal cancer screening and treatment program combining
many of the interventions discussed previously, including
insurance coverage, patient education and communication,
and patient navigation, to address the entire health care sys-
tem and its treatment of African American patients with
colorectal cancer. The state also partnered with underserved
community organizations to tailor programs locally and cre-
ate targeted marketing campaigns.
The results of this system-based approach were impres-
sive, with screening rates among African Americans increas-
ing from 48% to 74% and equaling the rate among whites.
In addition, the percentage of patients diagnosed at
advanced and regional stages among African Americans
declined from 79% to 40%, and the percentage diagnosed at
a local stage increased from 16% to 50%. Most importantly,
the mortality rate declined by 42% for African Americans,
and this resulted in a rate almost equal to that among whites
(P<.001 for African Americans, P5.002 for whites).
107
Significantly, this program was also found to be economi-
cally viable because cost savings from reduced cancer inci-
dence and the stage shift to cancers requiring less aggressive
treatment offset the cost of the program. As the authors con-
cluded, this model of a comprehensive, system-wide
approach to the racial mortality difference would lend itself
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to other cancers, and more research is needed to assess and
build such an approach to breast cancer.
Delivery System Reform
As demonstrated in the aforementioned studies, multifac-
eted interventions that address all stakeholders are needed
to close the racial disparity gap in breast cancer. The
Patient Protection and Affordable Care Act (PPACA)
emphasizes delivery system reform with a focus on the tri-
ple aim of better health, better health care, and lower
costs.
108
One component of this reform will be accountable
care organizations (ACOs). ACOs could potentially assist
in closing the racial mortality gap because groups of pro-
viders will take responsibility for improving the health of a
defined population and will be held accountable for the
quality of care delivered.
In the ACO model, an integrated network of providers,
led by primary care practitioners, will evaluate the necessity,
quality, value, and accountable delivery of specialty diag-
nostic and therapeutic procedures, including cancer care.
109
ACOs will also collect extensive patient data through the
meaningful use of medical records.
109
These detailed data
can then be used to shape locoregional protocols for clinical
decision making in oncology and can be used to evaluate
physician performance. Intermountain Healthcare is an
example of an organization that has had success with insti-
tuting these clinical protocols to highlight best practices
and improve the quality of care.
110
In breast cancer, oncolo-
gists will need to be prepared to develop and follow proto-
cols tailored for their communities, which will lead to
standardized, improved care for minority populations.
The oncology medical home is one example of an ACO
delivery system reform that has the potential to reduce the
racial mortality gap. The oncology medical home replaces
episodic care with long-term coordinated care and replaces
the fee-for-service model with a performance and out-
comes–based system. A key trait of the oncology medical
home is care that is continuously improved by measurement
against quality standards.
111
The model oncology home
accomplishes this by incorporating software to extract clini-
cal data as well as provider compliance with locoregional
guidelines to provide oncologists with feedback regarding
the quality of care that they are providing for their
patients.
112
Through this system reform, oncologists will
be held accountable for the care that they deliver, and it is
hoped that this will eliminate the delays, misuse, and
underuse of treatment. Trial oncology medical homes in
North Carolina and Michigan have yielded promising
results regarding improved care (fewer emergency depart-
ment visits and inpatient admissions) and high adherence
to national and practice-selected guidelines.
113,114
PPACA also increases funding for community health
centers and provides grants to support community health
workers; this highlights again the importance of place in
racial health care disparities.
115
Encouraging collaboration
between community health centers and academic institu-
tions, this funding could build bridges between minority
communities and high-quality health care institutions
while also improving patient communication and educa-
tion.
115
As this review has discussed, a failure to provide
culturally appropriate clinical information can lead to issues
with follow-up and adjuvant treatment compliance and fur-
ther widen the breast cancer racial mortality gap.
Conclusion
Delivery system reform has the potential to help close the
disparity gap by improving the quality of care delivered to
minority breast cancer patients. As Chin et al
116
describe in
their analysis of effective strategies for reducing health dis-
parities, successful interventions are “culturally tailored to
meet patients’ needs, employ multidisciplinary teams of
care providers, and target multiple leverage points along a
patient’s pathway of care.” ACOs have the financial incen-
tive to meet these features of a successful intervention and
improve quality across the continuum of breast cancer care.
Equity of care is a fundamental component of quality of
care, and efforts to reduce disparities will need to be inte-
grated into ACO quality improvement efforts. In the face
of this new era of organizational structures focused on coor-
dinated, population-based care, oncology providers put
themselves at financial risk if they do not position them-
selves for policy and reimbursement changes that reduce
disparities.
116
However, ongoing research will be needed to
ensure that as these changes are implemented, the racial
mortality gap in breast cancer tightens and that no vulnera-
ble patient populations are left out.
Precision Medicine for All
In addition, as discussed earlier in this review, there are dif-
ferences in the tumor biology and genomics of breast cancer
in African American patients. Beyond quality interventions,
initiatives to reduce the mortality gap should focus on pre-
cision medicine for all and making research strides to better
understand these biologic and genomic differences and tai-
lor breast cancer treatments to respond to these differences.
PPACA has taken steps in this direction as well by being
the first federal law to require group health plans and state-
licensed health insurance companies to cover standard-of-
care costs associated with participation in clinical trials.
117
The clinical trial regulations also expressly require plans to
show that administrative burdens are not used to create
barriers to cancer care for anyone who might benefit from
participation in a clinical trial.
115
The overarching goal of
this push to eliminate financial and administrative barriers
is to increase the enrollment of minority patients and
Closing the Racial Disparity Gap in Breast Cancer
234 CA: A Cancer Journal for Clinicians

especially those patients who do not live close to academic
medical centers. Community medical oncologists will be
called upon to facilitate and encourage clinical trial partici-
pation by their minority patients and should be supported
in this endeavor by academic medical centers. However,
with greater minority patient involvement, there should
also be further research on trial designs that lead to clini-
cally significant findings for minority patients. As Polite
et al
118
argue, at a bare minimum, basic sociodemographic
and detailed comorbidity information should be prospec-
tively collected and integrated with tumor and host biology
data to better examine racial differences in cancer
outcomes.
Initiatives are also needed to address the gap in referrals
to cancer risk clinics so that more data are available on
African American genetic variants and to create more
robust risk assessment models. Risk assessment relies on
predictive statistical models to estimate an individual’s risk
of developing cancer, and without accurate estimates of
mutation prevalence in minority subgroups, these models’
reliability is compromised.
119
As shown in a recent study at
the University of Chicago cancer risk clinic using targeted
genomic capture and next-generation sequencing, nearly
1 in 4 African American breast cancer patients referred to
the clinic had inherited at least one damaging mutation
that increased their risk for the most aggressive type of
breast cancer.
120
To identify damaging mutations after a
diagnosis of incurable breast cancer is failure of prevention.
As has been documented in Ashkenazi Jewish populations,
there is evidence of high rates of inherited mutations in
genes that increase the risk for aggressive breast cancers in
populations of African ancestry. This is a fertile area for
further research to better understand how these mutations
affect the clinical course of breast cancer, what targeted
interventions will increase the proportion of breast cancer
diagnosed at stage 1, and what molecularly targeted treat-
ments will produce a response in these tumors. Churpek
et al
120
also demonstrated the need for continued techno-
logical innovation to reduce the disparity gap because next-
generation sequencing is a faster and more cost-efficient
way to evaluate for multiple variants in many genes, and
this is particularly valuable for African Americans, who
tend to have greater genetic diversity.
121
The current
administration is also heralding this approach to cancer
care. In his 2015 State of the Union address, President
Obama announced a precision medicine initiative including
a request for $70,000,000 for the National Cancer Institute
to investigate genes that may contribute to the risk of
developing cancer.
122
African American women should
no longer be left behind in the push for personalized medi-
cine that caters to a patient’s tumor biology and genetic
profile.
In conclusion, there is an opportunity in the current cli-
mate of health care reform ushered in by the Affordable
Care Act to address many of the discussed elements leading
to the persistent racial mortality gap in breast cancer. We
have argued that 2 substantial factors lead to this eroding
gap. One is differences in tumor biology and genomics, and
the second is a quality difference in patterns of care. In
describing the perfect storm, Sebastian Junger
123
wrote
of the collision of 2 forces—a hurricane’s warm-air, low-
pressure system and an anticyclone’s cool-air, high-pressure
system—that combined to create a more powerful and
devastating meteorological force. Similarly, we argue that it
is the collision of these 2 factors, tumor biology and
genomics, with patterns of care that leads to the breast can-
cer mortality gap because the delays, misuse, and underuse
of treatment that we have underscored are of increased sig-
nificance when patients are presenting with more aggressive
forms of breast cancer. Interventions to close this gap will
take leaders at the patient, provider, payer, and community
levels to drive system change. Interventions can no longer
focus on the patient as the agent of change but must, as in
Delaware, involve the entire continuum of care. 䊏
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