Within-Stage Racial Differences in Tumor Size andNumber of Positive Lymph Nodes in Women WithBreast Cancer

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

1 Department of Epidemiology, Mailman Schoolof Public Health, New York, New York.

2 Department of Medicine, Mailman School ofPublic Health, Columbia University, New York,New York.

3 Herbert Irving Comprehensive Cancer Center,College of Physicians and Surgeons, MailmanSchool of Public Health, Columbia University,New York, New York.

4 Department of Biostatistics, Mailman School ofPublic 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.

M ajor advances in breast cancer screening, diagnosis, and treat-

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%

Address for reprints: Alfred I. Neugut, MD, PhD,Division of Medical Oncology, Columbia UniversityMedical Center, 722 West 168th Street, Room725, New York, NY 10032; Fax: (212) 305-9413;E-mail: ain1@columbia.edu

Supported by an R25 Award from the NationalCancer Institute (NCI) (CA94061 to R.B.M.), and aT32 Award (ULI RR024156 to R.B.M.) from agrant from the National Center for ResearchResources (NCRR) of the National Institutes ofHealth; a K07 Award from the NCI (CA95597 toD.H.); a K05 Award from the NCI (CA89155 toA.I.N.); a grant from the American Cancer Society(RSGT-01-024-04-CPHPS to A.I.N.); and a grantfrom the Department of Defense (BC043120 toA.I.N.).

Received April 5, 2007; revision received April18, 2007; accepted May 22, 2007.

ª 2007 American Cancer SocietyDOI 10.1002/cncr.22884Published online 13 August 2007 in Wiley InterScience (www.interscience.wiley.com).

1201

of black women were diagnosed with regional or dis-

tant disease.1 Some 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.3–13 For example, black women are more

likely than white women to be diagnosed with hor-

mone receptor-negative tumors with high nuclear

grade.3,5,6 Tumors 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.3,7 Studies 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 likely to discontinue

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.14 However, 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.15 In 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%.16 In 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 METHODSWe identified black and white women diagnosed

with histologically confirmed, invasive, AJCC17 stage

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-

able at: www.seer.cancer.gov/seerstat). The SEER

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-

istered patient.

We excluded patients diagnosed with sarcomas

or lymphomas of the breast (n 5 2). We also sequen-

tially excluded those with no tumor present

(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

nonspecified number of positive lymph nodes

(n 5 5258).

CovariatesTumor 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

at diagnosis as married or unmarried (single,

divorced, widowed, or separated). Residence in a

major metropolitan area was defined based on the

1202 CANCER September 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

Statistical AnalysisWe 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

nonnormally distributed data, the nonparametric

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).

RESULTSWe 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

cm in black versus white women, respectively

(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 T1-T3 breast cancer.

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

nodes.

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

TABLE 1Clinical 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

Sample size 256,174 100.0 21,861 91.5 234,313 8.5

TNM stage <.0001

I 127,659 49.7 8031 36.7 119,328 50.9

IIA 76,680 29.9 7355 33.6 69,325 29.6

IIB 41,371 16.2 4954 22.7 36,417 15.5

IIIA 10,764 4.2 1521 7.0 9243 3.9

Tumor size, cm

T1a (�0.5) 11,911 4.7 778 3.6 11,133 4.8 <.0001

T1b (0.5–1.0) 48,768 19.0 2746 12.6 46,022 19.6

T1c (1.5–2.0) 105,192 41.1 7867 36.0 97,325 41.5

T2 (2.5–5.0) 79,287 30.9 8842 40.4 70,445 30.1

T3 (>5.0) 11,016 4.3 1628 7.4 9388 4.0

Positive lymph nodes

0 170,158 66.5 12,657 57.9 157,501 67.6 <.0001

1–3 57,047 22.3 5857 26.8 51,190 21.9

4–9 19,484 7.6 2233 10.2 17,251 7.4

�10 9485 3.7 1114 5.1 8371 3.6

Histologic grade <.0001

Low 131,862 51.5 8487 38.8 123,375 52.7

High 84,775 33.1 9982 45.7 74,793 31.9

Unknown 39,537 15.4 3392 15.5 36,145 15.4

ER/PR <.0001

Negative 40,159 15.7 5948 27.2 34,211 14.6

Positive 164,694 64.3 10,977 50.2 153,717 65.6

Unknown 51,321 20.0 4936 22.6 46,385 19.8

Marital status* <.0001

Married 147,612 57.6 8648 39.6 138,964 59.3

Unmarried 108,562 42.4 13,213 60.4 95,349 40.7

Urban residence <.0001

Yes 212,872 83.1 20,560 94.1 192,312 82.3

No 43,302 16.9 1301 5.9 42,001 17.9

Mean/Median SD Mean/Median SD Mean/Median SD

Tumor size, cm 2.1/1.7 1.7 2.5/2.0 1.9 2.0/1.6 1.7

Lymph nodes examined 12.9/12.0 8.4 13.4/13.0 8.3 12.8/12.0 8.4

Positive lymph nodes

Lymph node 1/2 1.4/0.0 1.8/0.0 1.3/0.0

Lymph node 1 only 4.1/2.0 4.3/2.0 4.0/2.0

% Povertyy 8.6/7.5 11.0/12.4 8.4/7.1 <.0001

Median 59.7/60.0 55.7/55.0 60.0/60.0 <.0001

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.y Percentage of families with incomes below the poverty level in 2000.

1204 CANCER September 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

with improved mortality. The series of models

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

worse survival than whites across all stages of dis-

ease, but also that this disparity significantly

increases with each increase in TNM stage.

DISCUSSIONWe 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 sizeamong 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

TABLE

2Results

ofMultiva

riateAna

lysesAssessing

theAssoc

iation

Betwee

nRac

ean

dSu

rvival

inWom

enWithStag

eI-IIIA

BreastCan

cer,SE

ER,1

988–

2002

Variab

le

Mod

el1:

Rac

e

only

Mod

el2:

Rac

e+

stag

e

Mod

el3:

Rac

e+

tumor

size

1

lymph

node

s

Mod

el4:

Mod

el2+

mod

el3

Mod

el5:

Mod

el2

+clinical

andde

mog

raph

ic

charac

teristics

Mod

el6:

Mod

el3

+clinical

andde

mog

raph

ic

charac

teristics

Mod

el7:

Mod

el4

+clinical

andde

mog

raph

ic

charac

teristics

Mod

el8:

Mod

el5

+race

3stag

einteraction

term

s

HR

95%

CI

HR

95%

CI

HR

95%

CI

HR

95%

CI

HR

95%

CI

HR

95%

CI

HR

95%

CI

HR

95%

CI

Race

(Ref:w

hite)

Africa

nAm

erican

1.76

1.71

–1.81

1.56

1.51

–1.61

1.54

1.50

–1.59

1.54

1.50

–1.59

1.39

1.35

–1.43

1.39

1.35

–1.44

1.39

1.35

–1.44

1.26

1.19

–1.34

TNM

Stag

e(Ref:s

tage

I)

IIA

1.74

1.70

–1.78

1.19

1.14

–1.23

1.63

1.59

–1.67

1.14

1.10

–1.18

1.63

1.59

–1.67

IIB

3.16

3.08

–3.24

1.36

1.28

–1.44

2.90

2.82

–2.99

1.30

1.22

–1.38

2.86

2.78

–2.93

IIIA

4.85

4.68

–5.02

1.43

1.32

–1.55

4.38

4.23

–4.54

1.38

1.28

–1.50

4.24

4.08

–4.41

Tumor

size,c

m1.28

1.27

–1.29

1.21

1.20

–1.23

1.24

1.23

–1.25

1.18

1.17

–1.20

No.

ofpo

sitiv

elymph

node

s(Ref:0

)

1–3

1.49

1.23

–1.32

1.27

1.23

–1.32

1.49

1.45

–1.52

1.31

1.26

–1.36

4–10

1.97

1.89

–2.06

1.97

1.89

–2.06

2.28

2.21

–2.34

1.99

1.91

–2.08

101

2.94

2.81

–3.08

2.94

2.81

–3.08

3.38

3.26

–3.50

2.94

2.81

–3.09

Year

ofdiag

nosis

0.98

0.97

–0.98

0.98

0.98

–0.98

0.98

0.98

–0.98

0.98

0.98

–0.98

Tumor

grad

e(Ref:low

)

High

1.41

1.38

–1.45

1.36

1.33

–1.40

1.36

1.33

–1.39

1.36

1.33

–1.39

Unk

nown

1.10

1.07

–1.13

1.08

1.05

–1.11

1.08

1.05

–1.11

1.08

1.05

–1.11

ER/P

Rstatus

(Ref:p

ositive

)

Neg

ative

1.55

1.51

–1.59

1.58

1.54

–1.62

1.58

1.54

–1.62

1.58

1.54

–1.62

Unk

nown

1.13

1.11

–1.16

1.13

1.11

–1.16

1.13

1.11

–1.16

1.13

1.11

–1.16

Marita

lstatus(Ref:u

nmarried

*)0.82

0.80

–0.84

0.82

0.81

–0.84

0.82

0.81

–0.84

0.82

0.81

–0.84

Urban

reside

nce

0.98

0.96

–1.01

0.98

0.95

–1.00

0.98

0.95

–1.00

0.98

0.95

–1.00

Pove

rtyinde

xy

1.01

1.01

–1.01

1.01

1.01

–1.01

1.01

1.01

–1.01

1.01

1.01

–1.01

Race

-stage

interaction

Stag

eIIA3

race

1.06

0.98

–1.15

Stag

eIIB3

race

1.15

1.06

–1.25

Stag

eIIA3

race

1.30

1.17

–1.45

SEER

indica

tesSu

rveilla

nce,

Epidem

iology,a

ndEn

dRe

sults

prog

ram;H

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1206 CANCER 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.11,12,22 Bradley et al.23 found 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 of women with early-stage breast cancer

received <75% of their chemotherapy regimen and

that early termination was associated with both black

race and poorer overall survival.9 The 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.9,24 Obesity is also

associated with worse prognosis and is more preva-

lent in blacks.25–27 Finally, 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.28 SES is of parti-

cular concern when considering the frequency with

which multiple risk factors, including decreased

access to screening and treatment,29,30 comorbid

conditions,31 and a greater likelihood of biologically

unfavorable tumor characteristics,32–34 are 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.

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