Within-stage racial differences in tumor size and number of positive lymph nodes in women with breast cancer.
ABSTRACT Black women have higher breast cancer mortality rates, are more likely to be diagnosed at an advanced stage of disease, and have worse stage-for-stage survival than white women. It was hypothesized that differences in the tumor size and number of positive lymph nodes within each disease stage contribute to the survival disparity.
In the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, black and white women diagnosed with a first primary tumor (TNM stage I-IIIA breast cancer) between 1988 and 2003 were identified. The demographic and clinical characteristics were compared by race. Logistic regression models of the association between race and tumor size and lymph node status were developed. Cox proportional hazards models of the association between mortality and race, tumor size, lymph node status, and other covariates were also examined.
Among 256,174 SEER cases (21,861 black and 234,313 white women), more black than white women with lymph node-negative breast cancer had tumors measuring >or=2.0 cm. Adjusted for tumor size, more black than white women had >or=1 positive lymph nodes (odds ratio [OR], 1.24; 95% confidence interval [95% CI], 1.20-1.28). The age-adjusted and TNM stage-adjusted mortality rate ratio for blacks versus whites was 1.56 (95% CI, 1.51-1.61). Adjustment for within-stage differences in tumor size and lymph node involvement were found to have a negligible effect. With adjustment for additional covariates, the rate ratio was 1.39 (95% CI, 1.35-1.44). In addition, the rate ratio reflecting racial disparity increased as the stage of disease increased. CONCLUSIONS.: Adjusting for within-stage differences in tumor size and lymph node status did not appear to reduce the racial disparity. The finding that disparities increased with higher stage of disease suggests that interventions aimed at reducing these differences should target women with more advanced disease.
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ABSTRACT: The expression and biological consequences of Kaiso, a novel bi-modal transcription factor, in infiltrating ductal carcinomas (IDCs) have not been widely investigated. In the present study, we determined Kaiso expression and subcellular localization in 146 normal tissues, 376 IDCs, and 85 lymph node metastases. In IDCs, there was higher Kaiso expression in both the cytoplasmic and nuclear compartments, which correlated with age <48 (cytoplasmic p < 0.0093; nuclear p < 0.0001) and moderate differentiation (cytoplasmic p < 0.0042; nuclear p < 0.0001), as determined by Chi square analysis. However, only nuclear Kaiso correlated with poor prognostic factors, i.e., race (African Americans) (p < 0.0001), poor differentiation (p < 0.0001), and metastases (p < 0.0001). Nuclear Kaiso was also associated with worse overall survival (p < 0.0019), with African American patients displaying worse survival rates relative to Caucasian patients (p < 0.029). MCF-7 (non-metastatic), MDA-MB-468 (few metastases), and MDA-MB-231 (highly metastatic) breast cancer cells demonstrated increasing Kaiso levels, with more nuclear localization in the highly metastatic cell line. Over-expression of Kaiso in MCF-7 cells increased cell migration and invasion, but treatment of MDA-MB-468 and MDA-MB-231 cells with si-Kaiso decreased cell migration and invasion and induced expression of E-cadherin RNA and protein. E-cadherin re-expression was associated with a reversal of mesenchymal associated cadherins, N-cadherin and cadherin 11, as well as decreased vitamin expression. Further, Kaiso directly bound to methylated sequences in the E-cadherin promoter, an effect prevented by 5-aza-2-deoxycytidine. Immunofluorescence co-staining of poorly differentiated IDCs demonstrated that nuclear Kaiso is associated with a loss of E-cadherin expression. These findings support a role for Kaiso in promoting aggressive breast tumors.Clinical and Experimental Metastasis 02/2014; · 3.46 Impact Factor
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ABSTRACT: To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black-White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06-2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02-2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30-0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black-White BC survival disparity.Breast Cancer Research and Treatment 03/2014; · 4.47 Impact Factor
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ABSTRACT: To compare the difference between Uygur and Han patients with breast cancer in molecular subtype.International Journal of Clinical and Experimental Medicine 01/2014; 7(4):1116-21. · 1.42 Impact Factor
Within-Stage Racial Differences in Tumor Size and
Number of Positive Lymph Nodes in Women With
Russell McBride, MPH1
Dawn Hershman, MD, MS1,2,3
Wei-Yann Tsai, PhD4
Judith S. Jacobson, DrPH, MBA1,3
Victor Grann, MD, MPH1,2,3
Alfred I. Neugut, MD, PhD1,2,3
1Department of Epidemiology, Mailman School
of Public Health, New York, New York.
2Department of Medicine, Mailman School of
Public Health, Columbia University, New York,
3Herbert Irving Comprehensive Cancer Center,
College of Physicians and Surgeons, Mailman
School of Public Health, Columbia University,
New York, New York.
4Department of Biostatistics, Mailman School of
Public Health, New York, New York.
BACKGROUND. Black women have higher breast cancer mortality rates, are more
likely to be diagnosed at an advanced stage of disease, and have worse stage-for-
stage survival than white women. It was hypothesized that differences in the tu-
mor size and number of positive lymph nodes within each disease stage contri-
bute to the survival disparity.
METHODS. In the National Cancer Institute’s Surveillance, Epidemiology, and End
Results (SEER) database, black and white women diagnosed with a first primary
tumor (TNM stage I-IIIA breast cancer) between 1988 and 2003 were identified.
The demographic and clinical characteristics were compared by race. Logistic
regression models of the association between race and tumor size and lymph
node status were developed. Cox proportional hazards models of the association
between mortality and race, tumor size, lymph node status, and other covariates
were also examined.
RESULTS. Among 256,174 SEER cases (21,861 black and 234,313 white women),
more black than white women with lymph node-negative breast cancer had
tumors measuring ?2.0 cm. Adjusted for tumor size, more black than white
women had ?1 positive lymph nodes (odds ratio [OR], 1.24; 95% confidence
interval [95% CI], 1.20–1.28). The age-adjusted and TNM stage-adjusted mortality
rate ratio for blacks versus whites was 1.56 (95% CI, 1.51–1.61). Adjustment for
within-stage differences in tumor size and lymph node involvement were found
to have a negligible effect. With adjustment for additional covariates, the rate ra-
tio was 1.39 (95% CI, 1.35–1.44). In addition, the rate ratio reflecting racial dispar-
ity increased as the stage of disease increased.
CONCLUSIONS. Adjusting for within-stage differences in tumor size and lymph
node status did not appear to reduce the racial disparity. The finding that dispa-
rities increased with higher stage of disease suggests that interventions aimed at
reducing these differences should target women with more advanced disease.
Cancer 2007;110:1201–8. ? 2007 American Cancer Society.
KEYWORDS: racial disparities, stage, breast cancer, Surveillance, Epidemiology,
and End Results (SEER), survival, lymph nodes, tumor size.
ment have led to an improvement in survival over the past 20
years. However, despite a lower incidence rate of breast cancer,
black women have a notably higher mortality rate from breast can-
cer than white women. A large portion of this disparity is attributed
to more advanced stage at diagnosis among black women. Accord-
ing to the American Cancer Society’s annual report of cancer statis-
tics, 63% of white women but only 52% of black women were
diagnosed with localized disease, and 34% of white women but 45%
ajor advances in breast cancer screening, diagnosis, and treat-
Address for reprints: Alfred I. Neugut, MD, PhD,
Division of Medical Oncology, Columbia University
Medical Center, 722 West 168th Street, Room
725, New York, NY 10032; Fax: (212) 305-9413;
Supported by an R25 Award from the National
Cancer Institute (NCI) (CA94061 to R.B.M.), and a
T32 Award (ULI RR024156 to R.B.M.) from a
grant from the National Center for Research
Resources (NCRR) of the National Institutes of
Health; a K07 Award from the NCI (CA95597 to
D.H.); a K05 Award from the NCI (CA89155 to
A.I.N.); a grant from the American Cancer Society
(RSGT-01-024-04-CPHPS to A.I.N.); and a grant
from the Department of Defense (BC043120 to
Received April 5, 2007; revision received April
18, 2007; accepted May 22, 2007.
ª2007 American Cancer Society
Published online 13 August 2007 in Wiley InterScience (www.interscience.wiley.com).
of black women were diagnosed with regional or dis-
tant disease.1Some have ascribed the differences in
stage at diagnosis to racial differences in the utiliza-
tion of mammographic screening.2
However, even on a stage-for-stage basis, black
women have poorer survival than white women.3,4
Studies attempting to explain this disparity suggest
that differences in biologic characteristics of the tu-
mor and/or factors affecting quality of treatment are
responsible.3–13For example, black women are more
likely than white women to be diagnosed with hor-
mone receptor-negative tumors with high nuclear
grade.3,5,6Tumors from black women have been
shown to have a higher S-phase fraction, are more
likely to have cell cycle alterations (p53, p21, p16,
and Ki-67), and are more likely to have a basal cell,
triple-negative phenotype.3,7Studies by our group
and others have shown that black women also ap-
pear less likely to receive appropriate treatment.8–13
Black women are more likely than white to have de-
layed initiation of adjuvant chemotherapy or radia-
tion therapy, and more
chemotherapy prematurely, all of which can be asso-
ciated with worse survival.
TNM staging for breast cancer combines infor-
mation regarding tumor size, the number of positive
axillary lymph nodes, and distant metastasis; each of
these factors is reportedly associated with patient
prognosis.14However, each individual stage encom-
passes a wide range of tumor sizes and lymph node
involvement. For example, before the 2003 revision
of the American Joint Committee on Cancer (AJCC)
staging manual, stages IIA and IIB included patients
with any number of positive lymph nodes. The large
difference in survival between patients with stages
IIA or IIB disease was in fact a primary justifications
for the 2003 revision of the staging manual.15In an
observational study at the University of Chicago
spanning >50 years, researchers found that women
with stage IIA (T1N1) cancer and only 1 positive
lymph node had a disease-free survival of 78%,
whereas the survival of similarly staged women with
4 to 9 positive lymph nodes dropped to 39%.16In an
earlier Surveillance, Epidemiology, and End Results
(SEER)-based study that examined the correlation
between tumor size and number of positive lymph
nodes in 24,740 women, investigators reported that
the 5-year relative survival of women with T1 (<2.0
cm) tumors and 1 to 3 positive lymph nodes was in
the range of 87% to 96%, whereas women with simi-
larly sized tumors and ?4 lymph nodes had a 5-year
survival rate of 64%.14
We hypothesized that within-stage differences in
tumor size and lymph nodes between blacks and
whites may account for some of the stage-for-stage
disparities in survival that are observed. We used data
from the National Cancer Institute’s SEER database to
evaluate if the number of positive lymph nodes and
tumor size would explain racial disparities in survival.
MATERIALS AND METHODS
We identified black and white women diagnosed
with histologically confirmed, invasive, AJCC17stage
I-IIIA breast cancer between January 1, 1988, and
December 31, 2003 (n 5 290,345) in the SEER pro-
gram using SEER*Stat software (version 6.2.3) (avail-
program has recorded incident cancers since 1973,
but has only included AJCC staging information
since 1988, as well as cases from 9 registries from
Atlanta, Connecticut, Detroit, Hawaii, Iowa, New
Mexico, San Francisco-Oakland, Seattle-Puget Sound,
and Utah. In 1992 the program expanded to include
an additional 4 registry sites: San Jose-Monterey, Los
Angeles, Alaska Natives, and Rural Georgia. In 2000,
the SEER program was expanded again to include
the entire state of California as well as Kentucky,
Louisiana, and New Jersey. The SEER Public Use
Data include SEER incidence and population data
grouped by age, sex, race, year of diagnosis, and geo-
graphic area, and provide information regarding
stage of disease; tumor grade, size, and histology;
lymph node status; and overall survival for each reg-
We excluded patients diagnosed with sarcomas
or lymphomas of the breast (n 5 2). We also sequen-
tially excludedthose with
(n 5 190), microscopic foci (n 5 5560), no recorded
tumor size (n 5 1608), Paget disease of the nipple
(n 5 1), inflammatory breast cancer (n 5 227), no
reported lymph node dissection (n 5 20,947), or a
(n 5 5258).
Tumor size, number of positive lymph nodes, age,
and year of diagnosis were taken directly from the
SEER database. The histologic grade of the tumor
was categorized as high if it was grade 3 or 4, low if
it was 1 or 2, and unknown if it was not recorded.
Estrogen receptor (ER) and progesterone receptor
(PR) status was considered positive if either ER or PR
was recorded as positive, negative if both ER and PR
were negative, and unknown if neither measure was
recorded. Patients were categorized by marital status
divorced, widowed, or separated). Residence in a
major metropolitan area was defined based on the
1202CANCERSeptember 15, 2007 / Volume 110 / Number 6
county-level 2003 urban-rural continuum code pro-
vided by SEER. Patients were categorized as living in
a metropolitan area if their county of residence was
located in an urban area with a population of
?250,000. Patients were categorized by poverty index
based on the percentage of families below the pov-
erty level in their county of residence in the year
2000. SEER uses census data as surrogates for indivi-
dual data concerning residential and socioeconomic
factors. The validity of using census-based data for
this purpose has been discussed elsewhere.18–21
We used the chi-square statistical test to compare
the distributions of demographic (age, marital status,
metropolitan residence, socioeconomic status [SES])
and clinical characteristics (stage, tumor size, num-
ber of positive lymph nodes, number of lymph nodes
assessed, year of diagnosis, tumor grade, and ER/PR
status) of the breast cancer patients by race. We con-
ducted univariate analyses of tumor size and number
of positive lymph nodes to identify differences in their
distributions by race. We used the Kolmogorov-
Smirnoff procedure to test for the normality of the
distributions of the continuous variables and, for
Wilcoxon test to assess statistically significant differ-
ences in the distribution of tumor sizes between races.
We categorized tumor size in 0.5-cm increments from
0 to ?5.0 cm, and also used a chi-square test to evalu-
ate the significance of the difference in distribution of
white and black patients in these categories.
Logistic regression models were used to identify
predictors of dichotomized tumor size (<2 cm,
?2 cm) and of any versus no positive lymph nodes
within each stage. Cox proportional hazards models
were developed to estimate the differences in overall
mortality by race. First we adjusted for age at diag-
nosis. We then sequentially adjusted for 1) stage; 2)
tumor size and lymph nodes; 3) stage, size, and
lymph nodes; 4) stage plus clinical (year of diagnosis,
tumor grade, ER/PR status) and demographic charac-
teristics (marital status, metropolitan residence, zip
code level SES); and 5) stage, size, lymph nodes, and
clinical and demographic characteristics.
We included interaction terms for AJCC stage
and race in the Cox models. We then compared the
overall fit (22 log likelihood) of the model that
included variables for AJCC stage with that of the
model that also included continuous variables for tu-
mor size and number of positive lymph nodes. We
compared the overall fit (-2 Log likelihood ratio test)
of the model that included variables for AJCC stage
with that of the model that also included continuous
variables for tumor size and the number of positive
lymph nodes. By comparing the parameter estimates
for race between the 2 models, we were able to
assess the presence of residual confounding due to
racial differences in tumor size and lymph nodes
within each AJCC stage. All statistical analyses were
performed using SAS software for Windows (version
9.0.3; SAS Institute Inc, Cary, NC).
We identified 256,174 women (21,861 of whom were
black [8.5%] and 234,313 of whom were white
[91.5%]) and were diagnosed with stage I to stage
IIIA breast cancer who met our inclusion criteria.
The median follow-up was 45 months (interquartile
range, 22–92 months). The clinical and demographic
characteristics of the 2 groups are presented in Ta-
ble 1. The median age at diagnosis was 55 years
among black women and 60 years among white
women. The mean tumor sizes were 2.5 cm and 1.6
(P <.0001). The mean number of positive lymph
nodes among women with lymph node involvement
was 4.3 (standard deviation [SD] 5 4.9) among black
women and 4.0 (SD 5 4.9) among white women,
respectively (P <.0001). Across the range of tumor
stages, black women had fewer stage T1 tumors
(52.2% vs 65.9%), and significantly more stage T2
(40.4% vs 30.1%) and T3 (7.4% vs 4.0%) tumors com-
pared with whites (P <.0001). A greater proportion of
black women had at least 1 positive lymph node when
compared with whites (42.1% vs 32.4%; P <.0001).
Figure 1 illustrates the size (largest dimension in
cm) distribution of tumors by race among women
with lymph node-negative
Tumors measuring <2.0 cm in greatest dimension
accounted for 57% of cancers in white women but
only 44% of cancers in black women, whereas there
were comparatively fewer white women with tumors
measuring ?2.0 cm in size. Two-tailed P-values for
both the Wilcoxon rank sum test and the chi-square
test were less than .0001.
In a logistic regression model controlling for tu-
mor size, we found that black women were 24%
more likely than white women to have at least 1
positive lymph node (odds ratio [OR], 1.24; 95% con-
fidence interval [95% CI], 1.20–1.28). We tested the
possibility that this effect was due to white women
being more likely to undergo an axillary lymph node
dissection or having a greater number of lymph
nodes examined than blacks. The proportions of
black and white women meeting our other inclusion
criteria who were excluded from our analysis for ei-
ther having not undergone a lymph node dissection
Racial Disparities in Breast CA/McBride et al.1203
or being listed as having positive lymph nodes of
unspecified number did not differ statistically (9.4%
vs 9.2%; P 5.31). We found that black women have a
greater mean number of lymph nodes examined
when compared with whites (P <.0001). However,
black women were found to have a higher ratio of
positive lymph nodes to lymph nodes examined
when compared with whites (0.13 vs 0.10; P <.0001).
Figure 2 illustrates the association between the mean
number of positive lymph nodes and tumor size in
black and white women with lymph node-positive
disease. It shows that for the most commonly found
tumor sizes (1.0–2.0 cm), black women had a greater
mean number of positive lymph nodes than whites.
Among women diagnosed with tumors measuring
between 2.5 and 4.0 cm, black and white women had
a similar number of positive lymph nodes; however,
as tumor size increased above 4.0 cm, white women
were found to have significantly more positive lymph
Table 2 presents the results of our Cox propor-
tional hazards regression analysis of the association
between race and mortality in women with stages I
to stage IIIA breast cancer, adjusted for clinical and
Clinical and Demographic Characteristics of Women Diagnosed With Stage I-IIIA Breast Cancer by Race, SEER, 1988–2002 (N 5 256,174)
Total% Black% White%P
Tumor size, cm
Positive lymph nodes
Tumor size, cm
Lymph nodes examined
Positive lymph nodes
Lymph node 1/2
Lymph node 1 only
SEER indicates Surveillance, Epidemiology, and End Results program; ER, estrogen receptor; PR, progesterone receptor; SD, standard deviation; 1, positive; 2, negative.
* Unmarried indicates single, widowed, divorced, or separated at the time of diagnosis.
yPercentage of families with incomes below the poverty level in 2000.
1204CANCERSeptember 15, 2007 / Volume 110 / Number 6
tumor characteristics. All variables except metropoli-
tan residence were found to be significantly asso-
ciated with mortality at P <.0001. Only more recent
year of diagnosis and being married were associated
demonstrates that the age-adjusted survival disparity
between blacks and whites is reduced from 1.76
(95% CI, 1.71–1.81) to 1.56 (95% CI, 1.51–1.61) after
controlling for TNM stage, but it is not appreciably
changed after adjustment for residual differences in
tumor size or lymph node involvement (1.54; 95% CI,
1.50–1.59). The actual change in the race parameter
was e(0.01)(2.2% on the log scale), or 0.015 (<1% dif-
ference in the hazard ratio), well below the 10%
change in the beta coefficient commonly used to
assess the presence of confounding between the
nested and full models. Additional adjustment for tu-
mor grade, ER/PR status, year of diagnosis, marital
status, metropolitan residence, and poverty index
further reduced the black versus white hazards ratio
to 1.39 (95% CI, 1.35–1.44). Although not shown in
Table 2, we found that the addition of a variable for
the ratio of positive lymph nodes to lymph nodes
examined had no discernible effect on the survival
disparity between blacks and whites in either the full
or the nested models.
In addition, we identified a positive statistical
interaction between race and stage that demon-
strated that, as stage increases, the racial survival
disparity increases significantly more than would be
expected from multiplying their individual effects
(P <.0001), based on a generalized Wald test to
simultaneously test all 3 interaction terms. Figure 3
is a graph of the hazards ratios of blacks versus
whites from stage I to stage IIB disease after adjust-
ment for other known clinical and demographic con-
founders. It demonstrates not only that blacks have
The seriesof models
worse survival than whites across all stages of dis-
ease, but alsothat this
increases with each increase in TNM stage.
We found that within each category of TNM stage,
blacks had significantly larger tumors than whites. In
addition, among all women with lymph node-posi-
tive breast cancer, blacks had a significantly higher
mean number of positive lymph nodes, but that this
effect was only present among tumors measuring
<2.0 cm. Despite this, finer adjustment of the sur-
vival models to account for these within-stage differ-
ences appeared to have no additional effect on the
mortality hazards ratio for race. Although statistically
significant differences were observed within TNM
stage between black and white women with breast
cancer, from a clinical perspective these differences
were so modest as to have no measurable effect on
survival. Finally, we demonstrate that racial dispari-
ties in survival between black and white women with
breast cancer increase with later stage at diagnosis.
It has been well established that a proportion of
the racial disparity noted in outcome is due to differ-
ences in tumor characteristics and clinical and de-
mographic factors, which in our group resulted in a
drop in the black versus white mortality hazards ratio
from 1.76 to 1.39. Even after controlling for known
clinical and biologic factors that affect prognosis,
black women still had a 39% higher mortality rate.
Although black women were significantly more likely
than white women to have been diagnosed with
lymph node-positive disease, this association was
limited to tumors measuring 1.0 to 3.0 cm in largest
dimension. Among women with tumors measuring
FIGURE 1. Tumor size in cm among black and white women with T1-T3,
lymph node-negative breast cancer, SEER, 1988?2002. SEER indicates Sur-
veillance, Epidemiology, and End Results program.
FIGURE 2. Number of positive lymph nodes as a function of tumor size
among black and white women with lymph node-positive breast cancer,
SEER, 1988?2002. SEER indicates Surveillance, Epidemiology, and End Re-
sults program; *, statistically significant differences in tumor size between
Whites and Blacks (Chi-square p < .05).
Racial Disparities in Breast CA/McBride et al.1205
Results of Multivariate Analyses Assessing the Association Between Race and Survival in Women With Stage I-IIIA Breast Cancer, SEER, 1988–2002
Model 1: Race
Model 2: Race +
Model 3: Race +
tumor size 1
Model 2 +
Model 5: Model 2
Model 6: Model 3
Model 7: Model 4
Model 8: Model 5
+ race 3
Race (Ref: white)
TNM Stage (Ref: stage I)
Tumor size, cm
No. of positive lymph nodes (Ref: 0)
Year of diagnosis
Tumor grade (Ref: low)
ER/PR status (Ref: positive)
Marital status (Ref: unmarried*)
Stage IIA 3 race
Stage IIB 3 race
Stage IIA 3 race
SEER indicates Surveillance, Epidemiology, and End Results program; HR, hazards ratio; 95% CI, 95% confidence interval, Ref, reference group; ER, estrogen receptor; PR, progesterone receptor.
All models were adjusted for age at diagnosis.
The independent effects of all individual variables were significant at P < .0001 except residence in a large urban area (not significant).
* Unmarried indicates single, widowed, divorced, or separated at the time of diagnosis.
yPercentage of families with incomes below the poverty level in 2000.
1206CANCER September 15, 2007 / Volume 110 / Number 6
>4.0 cm, white women had significantly more posi-
tive lymph nodes than black women. This was an
unexpected finding. The finding that black women
with lymph node-positive breast cancer have more
positive lymph nodes overall compared with white
women appears to be driven by more lymph node
involvement in the most commonly diagnosed, smal-
ler tumor sizes.
A new interesting finding was the statistically sig-
nificant interaction between race and stage with
respect to mortality (P ? .0001). Figure 3 demon-
strates that as stage at diagnosis increases, the racial
disparity in survival also increases. One plausible ex-
planation for this effect is that when breast cancer is
diagnosed at a more advanced stage, curative therapy
is more complex, requiring more extensive surgery as
well as courses of both radiation and chemotherapy.
Studies have suggested that the disparity noted in
breast cancer survival is related to differences in the
quality of adjuvant treatment, treatment completion,
and adherence.11,12,22Bradley et al.23found that after
controlling for other covariates, black women were
less likely than whites to undergo surgery, despite
being more likely to have worse prognostic features.
Our group previously reported that a substantial frac-
tion ofwomen withearly-stage
received <75% of their chemotherapy regimen and
that early termination was associated with both black
race and poorer overall survival.9The factors that
prevent black women from receiving the same qual-
ity of care as white women may be exacerbated by
the more complex treatment regimens used for more
advanced breast cancer.
The current study had a number of limitations,
the majority of which reflected the limited range of
data collected by the SEER registry. Specifically, our
study could not account for differences in treatment.
Without data regarding treatment (surgical, adjuvant,
hormonal therapy, and supportive care), we were
unable to take the actual treatment received into
account. SEER data also do not include comorbid
conditions, which may be confounders of the corre-
lation between race and survival. Blacks are more
likely to have more comorbid conditions based on
the Charlson comorbidity index.9,24Obesity is also
associated with worse prognosis and is more preva-
lent in blacks.25–27Finally, the level of detail concern-
ing the SES of our population limits our ability to
understand its role in breast cancer survival. The
effect of SES is paradoxical in breast cancer, given
the fact that women of lower SES have both lower
incidence and lower survival rates.28SES is of parti-
cular concern when considering the frequency with
which multiple risk factors, including decreased
access to screening and treatment,29,30comorbid
conditions,31and a greater likelihood of biologically
unfavorable tumor characteristics,32–34are often clus-
tered together in individuals of lower SES. Given the
extent to which these socioeconomic disparities
coincide with race in our population, we cannot
address the extent to which our estimates of the
racial survival disparity are mediated by SES.
Although we were able to confirm that there are
statistically significant differences within stage of dis-
ease between black and white women with regard to
tumor size and lymph node involvement, these dif-
ferences are not clinically significant with respect to
survival over and above the standard AJCC stage
categories. Our finding that the racial survival dispar-
ity increased with greater stage of disease was unex-
pected. If this latter finding is confirmed, efforts
aimed at reducing racial disparities should focus on
eliminating barriers to quality care in black women
with higher-stage disease.
1.Ries LAG, Melbert D, Krapcho M, et al. (eds). SEER Cancer
Statistics Review, 1975–2004. Based on November 2006
SEER data submission, posted to the SEER web site, 2007.
Bethesda, MD: National Cancer Institute; 2007. Available
2.Smith-Bindman R, Miglioretti DL, Lurie N, et al. Does utili-
zation of screening mammography explain racial and eth-
nic differences in breast cancer? Ann Intern Med. 2006;144:
3.Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer
subtypes, and survival in the Carolina Breast Cancer Study.
4.Eley JW, Hill HA, Chen VW, et al. Racial differences in sur-
vival from breast cancer. Results of the National Cancer
Institute Black/White Cancer Survival Study. JAMA. 1994;
FIGURE 3. Relative racial disparity in survival on a stage-for-stage basis
for black and white women with stage I-IIIA breast cancer, SEER, 1988?
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1208 CANCER September 15, 2007 / Volume 110 / Number 6