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Racial differences in breast cancer survival: The interaction of socioeconomic status and tumor biology
Racial differences in breast cancer survival: The interaction of socioeconomic status and tumor biology Michael S. Simon, MD, MPH, and Richard Ko Severson, Pb_D Detroit, Michigan OBJECTIVE: Our purpose was to evaluate the effect of sociodemographic and clinical variables on survival rates of African-American and white women with breast cancer. STUDY DESIGN: Between 1988 and 1992 the Metropolitan Detroit Cancer Surveillance System identified 10,502 women (82% white and 18% African-American) in whom invasive breast cancer was diagnosed. Cox proportional hazards regression was used to estimate the relative risk of death for African-Americans comparec with whites after controlling for variables believed to influence survival. RESULTS;: African-American women were more likely than white women to have tumors that were of a more adwmced stage, a higher grade, and hormone receptor-negative. After controlling for age, tumor size, stage, histologic grade, census-derived socioeconomic status, and the presence of a residency training program at the treatment hospital, the relative risk of dying for African-Americans compared with whites was 1.68 (95% confidence interval, 1.27-2.23) for women less than 50 years of age, and 1.33 (95% confidence interval, 1.13-1.56) for women older than 50 years of age. CONCLUSIONS: Known factors that predict survival differences between African-Americans and whites are more prevalent among women less than 50 years of age, emphasizing the need to focus more attention on public health efforts directed toward younger women. (Am J Obstet Gyneco11997;176:$233-9.)
Key words:
Breast neoplasms, mortality, survival, e p i d e m i o l o g y
Despite the fact that they live in a country with o n e of the most advanced health care systems in the world, African-~Jalerican w o m e n in the U n i t e d States have significantly worse breast cancer survival rates than do their white c o u n t e r p a r t s J -5 A l t h o u g h survival rates for w o m e n with breast cancer have generally i m p r o v e d over time, the large gap in survival rates between African-American and white w o m e n has n o t c h a n g e d appreciably d u r i n g the past 30 years. 1 O f additional c o n c e r n are r e c e n t statistics :~ndicating that breast cancer i n c i d e n c e rates are increasing m o r e rapidly in y o u n g African-American w o m e n than in any o t h e r racial or ethnic g r o u p in the U n i t e d States. 2' 6 This c o m b i n a t i o n of increasing incid e n c e and p o o r survival rates is indicative o f a major public health p r o b l e m for y o u n g African-American women. T h e explanation for the p o o r e r survival rates of AfriFrom the Barbara Ann Karmanos Cancer Institute, Wayne State University. Supported in part by Karmanos Cancer Institute coregrant CA-22453 and the United Foundation of Detroit. Presented in part at the Thirty-first Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA., May 20-23, 1995. Adapted ir, part from Simon MS, Severson RK. Racial differences in survival offemale breast cancer in the Detroit Metropolitan Area. Cancer 1996;77:308-14. © 1996 American Cancer Society. Adapted with permission of Wiley-Liss, Inc., a subsidiary ofJohn Wiley and Sons, Inc. Reprint requests: Michael S. Simon, MD, MPH, Wayne State University School of Medicine, Division of Hematolog3 and Oncology, Harper Hospital-Room 513 Hudson, 3990John R. St., Detroit, M I 48201. Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 + 0 6/0/82171
can-Americans with breast cancer relative to white w o m e n is most likely multifactorial, potentially involving interactions between s o c i o e c o n o m i c a n d biologic influences. 6 O n e of the strongest r e c o g n i z e d prognostic indicators for breast cancer is stage at diagnosis, 7 and African-American w o m e n have b e e n consistently shown to have m o r e advanced disease at diagnosis than white women.l-5, 8-14 These differences in stage at diagnosis do not provide the entire explanation for the n o t e d survival differences, however, because survival rates for whites are h i g h e r than for African-Americans at each stage of disease.I-3, 9, a3 Dansey et al. 9 showed that survival differences between races can be explained by m o r e aggressive disease (larger t u m o r size and m o r e involved lymph nodes) within each stage a m o n g blacks. O t h e r investigators have f o u n d that African-American w o m e n are m o r e likely than whites to have m o r e biologically aggressive breast tumors, including a h i g h e r p r o p o r t i o n that are h o r m o n e receptor-negative, 2'1a'14 poorly differentiated, 2'11'15 high grade, 11'15 and have atypical nuclear features. ~°'15 R e c e n t investigations have shown that o t h e r potentially adverse prognostic indicators correlate with p o o r survival a m o n g African-American women, including nutritional markers, 11' 16 p53 g e n e alterations, ~7 and control of the cytochrome p450 enzyme system. 16 Whereas the bulk of evidence suggests that AfricanAmericans are diagnosed with a m o r e aggressive f o r m of breast cancer than are whites, we still d o n ' t know w h e t h e r these differences are mainly the result of endogS233
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T a b l e I. D i s t r i b u t i o n o f d e m o g r a p h i c a n d clinical characteristics by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d i n t h e D e t r o i t m e t r o p o l i t a n a r e a (1988-1992)
African-American Characteristic Age (yr) <50 50-64 65 + Marital status Married Widowed Divorced/separated Never married Unknown Census rank* Low Medium High Unknown Mammography history Done Not done Unknown
White
No.
%
No.
[
605 593 682
32.2 31.5 36.3
1917 2728 3977
22.2 31.6 46.1
727 418 279 348 108
38.7 22.2 14.8 18.5
5020 2134 664 663 141
58.2 24.8 7.7 7.7
1368 388 118 6
72.8 20.6 6.3
1274 3300 3964 84
14.8 38.3 45.9
858 131 891
86.7 13.2
4059 506 4057
88.9 11.1
I
%
<0.00001
<0.00001
<0.00001
0.149
*Census rank was categorized as low, medium or high, based on a composite of the percentage of persons over age 20 years who were high school graduates in that tract and the median household income for that census.
e n o u s factors o r w h e t h e r social o r s o c i o e c o n o m i c influe n c e s affect o u t c o m e . Several investigators have s t u d i e d the relationship between socioeconomic factors a n d survival.10,12, ls-27 Socioeconomic variables that have b e e n f o u n d to correlate with interracial survival differences include access to h e a l t h care or p a t i e n t delay in seeking treatment,10,12,18,19 social class (by census block group), 2°-22 education, 28 a n d income. 23'24 O t h e r investigators have shown that various o t h e r social a n d s o c i o e c o n o m i c att r i b u t e s s u c h as o c c u p a t i o n , z5 i n s u r a n c e status, 26 a n d characteristics o f t h e h o s p i t a l w h e r e t r e a t m e n t is received 27 c o r r e l a t e with b r e a s t c a n c e r survival. T h e o b j e c t i v e o f o u r analysis was to evaluate factors t h a t p r e d i c t survival differences b e t w e e n African-Americ a n a n d w h i t e w o m e n with b r e a s t c a n c e r in a n u r b a n c e n t e r with a large m i n o r i t y p o p u l a t i o n . W e were particularly i n t e r e s t e d in t h e i n f l u e n c e o f s o c i o e c o n o m i c status o n survival a n d w h e t h e r a n association existed b e t w e e n race a n d age.
Material and methods
Study eligibility. T h e study p o p u l a t i o n consisted o f b r e a s t c a n c e r cases d i a g n o s e d f r o m 1988 t h r o u g h 1992 a m o n g f e m a l e r e s i d e n t s o f m e t r o p o l i t a n D e t r o i t (Wayne, Oakland, and Macomb counties) and identified through t h e M e t r o p o l i t a n D e t r o i t C a n c e r Surveillance System (MDCSS).S Cases were selected f r o m 1988 t h r o u g h 1992 to best c o r r e l a t e with s o c i o e c o n o m i c d a t a d e r i v e d f r o m t h e 1990 census. Cases were a s c e r t a i n e d t h r o u g h t h e MDCSS, a f o u n d i n g m e m b e r o f t h e Surveillance, Epidemiology a n d E n d Results (SEER) p r o g r a m o f t h e Na-
tional C a n c e r Institute. x Eligible w o m e n were e i t h e r A f r i c a n - A m e r i c a n or white, h a d first p r i m a r y invasive b r e a s t cancer, a n d were alive at t h e t i m e o f diagnosis (i.e., cases a s c e r t a i n e d by d e a t h certificate a l o n e were e x c l u d e d ) . W o m e n with in situ b r e a s t c a n c e r were exc l u d e d b e c a u s e o f its p r e d i c t e d m i n i m a l i m p a c t o n b r e a s t c a n c e r survival rates, a n d w o m e n w h o h a d previously h a d p r i m a r y c a n c e r at any site ( e x c e p t n o n m e l a n o m a t o u s skin cancers) were e x c l u d e d b e c a u s e o f t h e p o t e n t i a l adverse affect o n survival rates. Variables. Data collection m e t h o d s u s e d at t h e MDCSS have b e e n d e s c r i b e d previously. 8 Variables evaluated i n c l u d e d d e m o g r a p h i c d a t a for t h e subjects, clinical i n f o r m a t i o n ( i n c l u d i n g first c o u r s e o f c a n c e r - d i r e c t e d t h e r a p y ) , a n d h o s p i t a l characteristics. D e m o g r a p h i c d a t a consisted o f age at diagnosis, race, m a r i t a l status, a n d a census-derived s o c i o e c o n o m i c r a n k (census r a n k ) t h a t was u s e d as a p r o x y for s o c i o e c o n o m i c status. C e n s u s rank, c a t e g o r i z e d as low, m e d i u m , o r h i g h , was c r e a t e d by c o m p i l i n g 1990 census d a t a for t h e p r o p o r t i o n o f h i g h s c h o o l g r a d u a t e s o l d e r t h a n age 20 years a n d m e d i a n h o u s e h o l d i n c o m e . 2°-22' 28 Clinical i n f o r m a t i o n i n c l u d e d past m a m m o g r a p h y use, t u m o r stage, t u m o r size, l y m p h n o d e status, histologic features, grade, a n d h o r m o n e ( e s t r o g e n a n d progestero n e ) r e c e p t o r stares. C o d i n g for m a m m o g r a p h y history was i n i t i a t e d i n 1990 a n d was classified as e i t h e r d o n e o r n o t d o n e . T u m o r staging (local, regional, or distant) was classified a c c o r d i n g to SEER guidelines, w h i c h have been d e s c r i b e d previously. 8 L y m p h n o d e i n v o l v e m e n t was c o d e d as e i t h e r n o involved n o d e s , axillary n o d e involve-
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Table II. Distribution of clinical characteristics by race a m o n g w o m e n with invasive breast cancer diagnosed in the Detroit m e t r o p o l i t a n area (1988-1992)
African-American Characteristic Tumor size T1 T2 T3 T4 Unlmown Lymph node status Zero Axi?[lary Disl~nt Unknown Stage Local Regional Remote Unknown Histologic type Invasive ductal Other Estrogen receptor* Positive Negative Unknown Progesterone receptor* Positive Negative Unknown Histologic grade One Two Three Four Unknown
No.
White No.
%
p
789 698 187 22 184
46.5 41.2 11.0 1.3
4933 2505 420 54 710
62.3 31.7 5.3 0.7
909 723 19 229
55,1 43.8 1.1
5073 2754 50 745
64.4 35.0 0.6
1007 719 119 35
53.6 38.2 6.3
5401 2858 293 70
62.7 33.1 3,4
<.00001
1304 576
69.4 30.6
6053 2569
70.2 29,8
0.49
535 343 1012
60.9 39.1
3185 850 4587
78,9 21.1
<0.00001
467 403 1010
53.7 46.3
2690 1261 4671
68.1 31,9
<0.00001
59 288 510 51 972
3.2 15.3 27.1 2.7 51.7
368 1245 1427 129 5473
4.3 14.4 16.6 1.5 63.2
0.00001
<0.00001
<0.00001
*Hormone receptor values were only available for women diagnosed in 1990 or later. The positive category included the cases that were categorized as positive or borderline. ment, or distant n o d e involvement (including internal m a m m a r J nodes and o t h e r distant sites). Estrogen and p r o g e s t e r o n e r e c e p t o r status were classified as either positive (including those that were borderline) or negative. R e c o r d of h o r m o n e r e c e p t o r results were kept only f r o m 1990 forward. I n f o r m a t i o n on cancer-directed therapy i n c l u d e d data on the primary surgery, radiation therapy, c h e m o t h e r apy, and h o r m o n a l therapy. Surgical p r o c e d u r e codes i n c l u d e d partial mastectomy (with or without axillary lymph n o d e dissection), simple mastectomy (without dissection of axillary lymph nodes), m o d i f i e d radical mastectomy, radical mastectomy, and o t h e r (including subcutaneous mastectomy or surgery to o t h e r or distant sites). Primary radiotherapy was delivered postoperatively to the affected breast, and c h e m o t h e r a p y and h o r m o n a l therapy were based on initial and follow-up abstracts. No detailed data were available r e g a r d i n g therapeutic dosage, duration, or exact p o r t of t r e a t m e n t for radiation. I n f o r m a t i o n on hospital characteristics p e r t a i n e d to the institution at which the patient received h e r first
course of cancer-related therapy. If the subject was treated at m o r e than one hospital, priority was given to the hospital where it was estimated that the w o m a n would be most likely to have o n g o i n g care for breast cancer (i.e., the hospital where the definitive breast surgery occurred, a larger hospital, or a hospital with a residency training p r o g r a m ) . Hospitals were categorized by n u m b e r of beds and residency training status according to guidelines in the A m e r i c a n Hospital Association Guide to the Health Care Field. 29 I n f o r m a t i o n on the p r o p o r t i o n of Medicare a n d / o r Medicaid patients discharged f r o m each hospital was used t o estimate subject insurance status. These data were o b t a i n e d from the SEER Patterns of Care Study and were originally used by the H e a l t h Care Financing Administration to d e t e r m i n e r e i m b u r s e m e n t on the basis o f hospital discharges. 3° A hospital with a h i g h e r p r o p o r t i o n of Medicaid a n d / o r Medicare discharges is assigned a h i g h e r n u m b e r on a 1 to 9 scale. Design and analysis. T h e primary o u t c o m e variable was overall survival ( m e a s u r e d in m o n t h s ) , which was the
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T a b l e III, D i s t r i b u t i o n o f t r e a t m e n t m o d a l i t i e s by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d in t h e D e t r o i t m e t r o p o l i t a n a r e a (1988-1992
African-American Characteristic Surgery Partial mastectomy* Simple mastectomy Modified radical mastectomy Radical mastectomy Other t Unknown Chemotherapy + Yes No Radiation therapy + Yes No Hormonal therapy + Yes No
No.
]
White
%
No.
536 75 1201 5 15 48
29.3 4.1 65.5 0.3 0.8
2811 259 5094 18 35 405
34.2 3.2 62.0 0.2 0.4
0.00007
499 1381
26.5 73.5
1732 6890
20.1 79.9
<0.0000l
522 1358
27.8 72.2
2495 6127
28.9 71.1
0.309
428 1452
22.8 77.2
1808 6814
21.0 79.0
0.085
*The partial mastectomy category includes those with or without axillary lymph node resection and subcutaneous mastectomy. t T h e "other" category includes subcutaneous mastectomy or surgery for regional or distant disease. ~No detailed information was included in the SEER database regarding therapeutic dosage, duration, or exact port of treatment for radiation. T a b l e IV. D i s t r i b u t i o n o f h o s p i t a l variables by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d in t h e D e t r o i t m e t r o p o l i t a n area (1988-1992)
African-American Characteristic Hospital size (No. beds) <200 >200 Residency training No Yes Proportion of Medicaid a n d / o r Medicare discharges* 1 2 3 4 5+
White
No.
%
No.
%
P
156 1724
8.3 91.7
1447 7175
16.8 83.2
<0.00001
420 1460
22.3 77.7
2808 5814
32.6 67.4
<0.00001
261 335 340 565 379
13.9 17.8 18.1 30.1 20.1
5273 1772 969 496 112
61.2 20,6 11,2 5.8 1.3
<0.00001
*This information was derived by the Health Care Financing Administration and used for the SEER Patterns of Care study. 3° A hospital with a higher proportion of Medicaid a n d / o r Medicare discharges is assigned a higher number on a 1 to 9 scale. interval b e t w e e n date o f diagnosis a n d date o f last activity or d e a t h f r o m any cause. M e t h o d s u s e d by t h e MDCSS to ascertain follow-up have b e e n d e s c r i b e d previously. 3 Overall survival rates r a t h e r t h a n b r e a s t c a n c e r - s p e c i f i c survival rates were u s e d as a n o u t c o m e b e c a u s e o f e x p e c t e d i n c o n s i s t e n t r e p o r t i n g o n t h e basis o f d e a t h certificates. T h i s m e t h o d o f a s c e r t a i n i n g survival h a s b e e n u s e d by o t h e r s a n d has b e e n f o u n d to show c o m p a r a b l e results to analyses t h a t use b r e a s t c a n c e r specific survival rates, u U n i v a r i a t e analyses were u s e d to assess differences b e t w e e n p o t e n t i a l c o n f o u n d i n g variables a n d race (Tables I, II, III, a n d IV). 31 Cox p r o p o r t i o n a l h a z a r d s
r e g r e s s i o n was u s e d to e s t i m a t e t h e relative risk o f d e a t h f r o m any cause in A f r i c a n - A m e r i c a n w o m e n c o m p a r e d with white w o m e n as d e s c r i b e d previously. 3' 3z I n f o r m a tion o n past use o f m a m l n o g r a p h y a n d h o r m o n e receptor status were n o t i n c l u d e d in t h e Cox m o d e l b e c a u s e data were available only for w o m e n d i a g n o s e d b e g i n n i n g in 1990. Axillary l y m p h n o d e status was also n o t u s e d in the model because detailed information on the number o f involved axillary l y m p h n o d e s was n o t available a n d it was e x p e c t e d t h a t a h i g h d e g r e e o f colinearity w o u l d exist b e t w e e n axillary l y m p h n o d e status a n d t u m o r stage. Data o n c a n c e r t h e r a p y f r o m t h e SEER registry were c o n s i d e r e d i n c o m p l e t e b e c a u s e m o s t c h e m o t h e r -
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apy and h o r m o n a l therapy administered for breast cancer are given on an outpatient basis, usually at a private office, and thus these data were n o t i n c l u d e d in the multivariate model. Potential interactions between race and o t h e r indep e n d e n t variables (age g r o u p and hospital size) were assessed and the statistical significance of interaction terms were evaluated with use of likelihood ratio tests. T h e appropriateness of the p r o p o r t i o n a l hazards ass u m p t i o n was assessed with use of the Breslow-Day test for the h o m o g e n e i t y of relative risks, which showed p r o p o r t i o n a l hazards t h r o u g h 48 m o n t h s after diagnosis. 3a T h e r e f o r e all analyses using Cox p r o p o r t i o n a l hazards models refer to events o c c u r r i n g up t h r o u g h 48 months.
Results F r o m 1988 t h r o u g h 1992, a total of 10,715 newly diagnosed cases of invasive breast cancer were identified in the Detroit m e t r o p o l i t a n area. T h e analyses r e p o r t e d h e r e include only the cases that were diagnosed a m o n g white (82%) or African-American (18%) w o m e n and excluded w o m e n who were of a n o t h e r or u n k n o w n racial category (n = 213). Table I lists d e m o g r a p h i c characteristics of the study cohort. African-American w o m e n were significantly m o r e likely than white w o m e n to be young, single, and to reside in a census tract that had a low s o c i o e c o n o m i c rank. No a p p a r e n t differences existed by race for aast m a m m o g r a p h y use. Table II lists the distribution of clinical characteristics by race. African-American w o m e n were m o r e likely than white w o m e n to have m o r e aggressive disease as n o t e d by m o r e advanced stage at diagnosis (i.e., larger tumors and a h i g h e r p r o p o r t i o n with axillary n o d e - p o s i t i v e tumors), tumors of a h i g h e r grade, and m o r e tumors that were h o r m o n e r e c e p t o r - n e g a t i v e . No differences in histologic t u m o r type (invasive ductal versus other) were f o u n d by race. Table III lists the use of cancer-directed t r e a t m e n t by race. African-Americans were less likely to have a partial mastectomy (with or without axillary lymph n o d e dissection) than were whites. African-Americans were aiso m o r e likely to have received c h e m o t h e r a p y than were whites. No statistically significant differences in t r e a t m e n t with radiation therapy or h o r m o n a l therapy were f o u n d by race. As indicated in Table IV, AfricanA m e r i c a n w o m e n were m o r e likely to be diagnosed or to receive their primary therapy at larger hospitals, as well as hospitals that had residency training programs. Hospitals at which African-American w o m e n were treated were also m o r e likely to have treated (discharged) a larger p r o p o r t i o n of patients who had e n t i t l e m e n t insurance (Medicare a n d / o r Medicaid) than did hospitals at which white w o m e n were treated. An evaluation of Kaplan-Meier survival curves for African-American and white w o m e n with breast cancer
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Table V. Results of age-specific models of the risk of death a m o n g blacks and whites /
Characteristic
Age <50 yr Unadjusted Race (black vs. white) Multivariate adjusted* Race (black vs. white) Age ->50 yr Unadjusted Race (black vs. white) Multivariate adjusted* Race (black vs. white)
Relative | 95 % Confidence risk .1 inlerual
2.35
1.88-2.93
1.68
1.27-2.23
1.66
1.46-1.88
1.33
1.13-1.56
*Multivariate models adjusted for age, tumor size, stage, histologic grade, census rank, and residency" training. stratified by stage showed that survival rates were significantly better for white w o m e n with local and regional stage disease (log rank p = 0.0001). No statistically significant differences in survival rates for African-American and white w o m e n with r e m o t e stage disease were f o u n d (log rank p = 0.3) (data n o t shown).a Multivariate m o d e l i n g showed a significant interaction between age group ( < 5 0 years vs. ---50 years) and race (p = 0.005) (Table V). Each m o d e l provides the unadjusted relative risk of death a m o n g African-American w o m e n c o m p a r e d with white w o m e n and the adjusted relative risk controlling for age, t u m o r size, stage, histologic grade, census rank, and the presence of a residency training p r o g r a m at the t r e a t m e n t hospital. T h e relative risks o f dying for young African-American w o m e n was greater than those for older African-American w o m e n (adjusted relative risk 1.68 versus 1.33, respectively). A d j u s t m e n t for marital status, the n u m b e r of beds in the hospital, and the p r o p o r t i o n of patients discharged who received Medicaid or Medicare benefits had n o further impact on mortality differences between African-American w o m e n and white women. No significant differences in survival for African-American or white w o m e n who lived b e y o n d 48 m o n t h s after the cancer was diagnosed were found.
Comment O u r results c o n c u r with findings of o t h e r reports that show a substantially worse mortality e x p e r i e n c e a m o n g African-American w o m e n with breast cancer c o m p a r e d with white women. 4-a' 9, xl, 13 To date a completely satisfactory explanation for these mortality trends has n o t b e e n found, although n u m e r o u s investigations reveal a n u m b e r of potentially interesting explanatory variables including b o t h social or s o c i o e c o n o m i c < 10, 1~-20,22-25 and biologic influences. 5' 8-H, 13, 17 It is possible that socioecon o m i c differences between African-American and white w o m e n are manifested as differences i n the biologic nature of the tumors, which results in a p o o r e r overall o u t c o m e for African-American women. O n e e x a m p l e of
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this hypothesis is t h e r e l a t i o n s h i p b e t w e e n dietary habits i n f l u e n c e d by c u l t u r a l n o r m s a n d b r e a s t c a n c e r survival differences b e t w e e n A f r i c a n - A m e r i c a n a n d w h i t e women. 5 I n o u r analysis we were u n a b l e tq evaluate several p o t e n t i a l e x p l a n a t o r y variables for b r e a s t c a n c e r survival rates b e c a u s e o f limitations in t h e SEER data. S o m e investigators have s u g g e s t e d t h a t issues r e l a t e d to access to h e a l t h care 18 a n d p a t i e n t delay i n s e e k i n g treatmentl0, 19 m a y have a n adverse i m p a c t o n stage o f disease at t h e t i m e o f diagnosis. I n fact, several investigators have s u g g e s t e d t h a t race itself h a s a m i n i m a l role i n d e t e r m i n ing b r e a s t c a n c e r survival rates after a d j u s t m e n t for disparities in i n c o m e 2~'25 a n d e d u c a t i o n . 23 However, racial differences in rates o f b r e a s t c a n c e r survival cont i n u e to b e a m a j o r p r o b l e m affecting t h e AfricanA m e r i c a n c o m m u n i t y a n d s h o u l d c o n t i n u e to b e a focus in f u t u r e h e a l t h care p l a n n i n g efforts. 22 A f r i c a n - A m e r i c a n w o m e n with b r e a s t c a n c e r in o u r study p o p u l a t i o n were m o r e likely t h a n white w o m e n to reside in a n a r e a with a low s o c i o e c o n o m i c level, to b e h o s p i t a l i z e d at a n i n s t i t u t i o n t h a t p r o v i d e s a h i g h prop o r t i o n o f care for t h e i n d i g e n t , a n d to have a d v a n c e d stage t u m o r s a n d aggressive t u m o r s (i.e., a h i g h e r prop o r t i o n with h o r m o n e r e c e p t o r negativity at diagnosis). A l t h o u g h i n f o r m a t i o n o n c a n c e r t r e a t m e n t in t h e SEER registry is n o t c o m p l e t e , o u r d a t a d e m o n s t r a t e d t h a t A f r i c a n - A m e r i c a n w o m e n r e c e i v e d t h e s a m e or m o r e aggressive c a n c e r - r e l a t e d t r e a t m e n t t h a n d i d white women. O u r results i n d i c a t e d t h a t survival differences b e t w e e n A f r i c a n - A m e r i c a n a n d white w o m e n are especially i m p o r t a n t for w o m e n in t h e first 4 years after diagnosis, in t h o s e with early stage disease, a n d for w o m e n in w h o m t h e c a n c e r was d i a g n o s e d w h e n they were less t h a n 50 years o f age. Interestingly, o u r f i n d i n g s r e v e a l e d t h a t A f r i c a n - A m e r i c a n w o m e n w h o survive l o n g e r t h a n 48 m o n t h s have survival rates similar to t h o s e o f white w o m e n . F u r t h e r analyses o f l o n g - t e r m survival rates a m o n g A f r i c a n - A m e r i c a n w o m e n m a y p r o v i d e i n s i g h t as to t h e factors t h a t m i g h t p r e d i c t i m p r o v e d survival rates for all A f r i c a n - A m e r i c a n w o m e n with b r e a s t cancer. The larger impact on mortality seen among young A f r i c a n - A m e r i c a n w o m e n m a y b e t h e r e s u l t o f different social a n d o r c u l t u r a l i n f l u e n c e s t h a t affect y o u n g e r women more than older women. These findings indicate t h e n e e d to focus m o r e a t t e n t i o n o n p u b l i c h e a l t h efforts for y o u n g e r w o m e n to achieve a large i m p a c t o n racial differences in b r e a s t c a n c e r survival rates. T h e s e efforts s h o u l d i n c l u d e i m p r o v e m e n t in c o m m u n i t y e d u c a t i o n a b o u t t h e i m p o r t a n c e o f early d e t e c t i o n ( a n d t h e fact t h a t b r e a s t c a n c e r c a n b e c u r e d if d e t e c t e d early), i m p r o v e m e n t in access to s c r e e n i n g m a m m o g r a m s , a n d b r o a d e n i n g o f s u p p o r t for n e w a n d existing b r e a s t can-
June ]997 Am J Obstet Gynecol
cer p r e v e n t i o n trials t h a t i n c l u d e all c o m m u n i t i e s o f women.
REFERENCES 1. Ries LAG, Miller BA, Hankey BF, Kosary CL, Harras A, Edwards BK, et al, editors. Cancer statistics review: 19731991. National Institutes of Health; 1994. Publication No. ' 94-2789. 2. Eley JR, Hill HA, Chen VW, Austin DF, Wesley MN, Muss HB, et al. Racial differences in survival from breast cancer: results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 1994;272:947-54. 3. Simon MS, Severson RK. Racial differences in survival of female breast cancer in the Detroit metropolitan area. Cancer 1996;77:308-14. 4. Freeman HP, Wasfie TJ. Cancer of the breast in poor black women. Cancer 1989;63:2562-91 5. Coates RJ, Clark WS, EleyJW, Greenberg RS, Huguley CM, Brown RL. Race, nutritional status, and survival from breast cancer. J Natl Cancer Inst 1990;82:1684-92. 6. Moormeier J. Breast cancer in black women. Ann Intern Med 1996;124:897-905. 7. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181-7. 8. Chen F, Trapido EJ, Davis K. Differences in stage at presentation of breast and gynecologic cancers among whites, blacks, and Hispanics. Cancer 1994;73:2838-42. 9. Dansey RD, Hessel PA, Browde S, Lange M, Derman D, Nissenbaum M, et al. Lack of a significant independent effect of race on survival in breast cancer. Cancer 1988;61:1908-12. 10. Hunter CP, Redmond CK, Chen VW, Austin DF, Greenberg RS, Correa P, et al. Breast cancer: factors associated with stage at diagnosis in black and white women. J Natl Cancer Inst 1993;85:1129-37. 11. Ownby He, Frederick J, Russo J, Brooks SC, Swanson GM, Heppner GH, et al. Racial differences in breast cancer patients. J Natl Cancer Inst 1985;75i55-60. 12. Jones BA, Kasl SV, Curnen MGM, Owens PH, Dubrow R. Can marnmography screening explain the race difference in stage at diagnosis of breast cancer? Cancer 1995;75:2103-13. 13. Natarajan N, Nemoto T, Mettlin C, Murphy GP. Racerelated differences in breast cancer patients: results of the 1982 National Survey of Breast Cancer by the American College of Surgeons. Cancer 1985;56:1704-9. 14. Stanford JL, Greenberg RS. Breast cancer incidence in young women by estrogen receptor status and race. Am J Public Health 1989;79:71-3. 15. Chen VW, Correa P, Kurman RJ, Wu X, EleyJW, Austin D, et al. Histological characteristics of breast carcinoma in blacks and whites. Cancer Epidemiol Biomarkers Prev 1994; 3:127-35. 16. Taioli E, Trachman J, Chen X, Toniolo P, Garte SJ. A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res 1995;55:3757-8. 17. Shiao Y, Chen VW, Scheer WD, Wu XC, Correa P. Racial disparity in the association of p53 gene alterations with breast cancer survival. Cancer Res 1995;55:1485-90. 18. Zaloznik AJ. Breast cancer stage at diagnosis: caucasian versus Afro-Americans. Breast Cancer Res Treat 1995;34:195-8. 19. Gregorio DI, Cummings KM, Michalek A. Delay, stage of disease, and survival among white and black women with breast cancer. Am J Public Health 1983;73:590-3. 20. Bassett MT, Krieger N. Social class and black-white differences in breast cancer survival. A m J Public Health 1986;76: 1400-3.
21. Dayal HH, Power RN, Chiu C. Race and socio-economic status in survival from breast cancer. J Chronic Dis 1982;35: 675-83. 22. Walker AP, Neal L, Ausman RK, Whipple J, Doherty B. Per
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23. 24.
25. 26.
27.
capita, income in breast cancer patients. J Natl Med Assoc 1989;81:1065-8. Cella DF, Orav EJ, Kornblith AB, HotlandJC, Silberfarb PM, Lee K~N, et al. Socioeconomic status and cancer survival. J Clin Oncol 1991;9:1500-9. Ansell D, Whitman S, Lipton R, Cooper R. Race, income and survival from breast cancer at two public hospitals. Cancer 1993;72:2974-8. Karja'~.alnen S, Pukkala E. Social class as a prognostic factor in breast cancer survival. Cancer 1990;66:819-26. AyanianJZ, Kohler BA, Abe T, Epstein AM. The relationship between health insurance coverage and clinical outcomes among women with breast cancer. N EnglJ Med 1993;329: 326-31. Lee-Feldstein A, Anton-Culver H, Feldstein PJ. Treatment differences and other prognostic factors related to breast cancer survival. JAMA 1994;271:1163-8.
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28. U.S. Bureau of the Census. Statistical abstract of the United States. 3rd ed. Washington (DC): The Bureau, 1991. 29. American Hospital Association. 1990 American Hospital Associadon guide to the health care field. Chicago: The Association, 1991. 30. Department of Health and Human Services. Surveillance, Epidemiology, and End Results Patterns of Care Study. Bethesda (MD): National Institute of Health, National Cancer Institute; 1990. Report No. 20892. 31. Neter J, Wasserman W, Kutner M. Applied linear statistical models: regression, analysis of variance and experimental design. 2nd ed. Homewood (IL): Richard D. Irwin; 1985. 32. Cox DR, Oakes DO. Analysis of survival data. London: Chapman and Hall; 1984. 33. Breslow NE, Day NE. Statistical methods in cancer research: volume 1: the analysis of case-control studies. Lyon, France: International Agency for Research on Cancer; 1980.
Key words:
Breast neoplasms, mortality, survival, e p i d e m i o l o g y
Despite the fact that they live in a country with o n e of the most advanced health care systems in the world, African-~Jalerican w o m e n in the U n i t e d States have significantly worse breast cancer survival rates than do their white c o u n t e r p a r t s J -5 A l t h o u g h survival rates for w o m e n with breast cancer have generally i m p r o v e d over time, the large gap in survival rates between African-American and white w o m e n has n o t c h a n g e d appreciably d u r i n g the past 30 years. 1 O f additional c o n c e r n are r e c e n t statistics :~ndicating that breast cancer i n c i d e n c e rates are increasing m o r e rapidly in y o u n g African-American w o m e n than in any o t h e r racial or ethnic g r o u p in the U n i t e d States. 2' 6 This c o m b i n a t i o n of increasing incid e n c e and p o o r survival rates is indicative o f a major public health p r o b l e m for y o u n g African-American women. T h e explanation for the p o o r e r survival rates of AfriFrom the Barbara Ann Karmanos Cancer Institute, Wayne State University. Supported in part by Karmanos Cancer Institute coregrant CA-22453 and the United Foundation of Detroit. Presented in part at the Thirty-first Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA., May 20-23, 1995. Adapted ir, part from Simon MS, Severson RK. Racial differences in survival offemale breast cancer in the Detroit Metropolitan Area. Cancer 1996;77:308-14. © 1996 American Cancer Society. Adapted with permission of Wiley-Liss, Inc., a subsidiary ofJohn Wiley and Sons, Inc. Reprint requests: Michael S. Simon, MD, MPH, Wayne State University School of Medicine, Division of Hematolog3 and Oncology, Harper Hospital-Room 513 Hudson, 3990John R. St., Detroit, M I 48201. Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 + 0 6/0/82171
can-Americans with breast cancer relative to white w o m e n is most likely multifactorial, potentially involving interactions between s o c i o e c o n o m i c a n d biologic influences. 6 O n e of the strongest r e c o g n i z e d prognostic indicators for breast cancer is stage at diagnosis, 7 and African-American w o m e n have b e e n consistently shown to have m o r e advanced disease at diagnosis than white women.l-5, 8-14 These differences in stage at diagnosis do not provide the entire explanation for the n o t e d survival differences, however, because survival rates for whites are h i g h e r than for African-Americans at each stage of disease.I-3, 9, a3 Dansey et al. 9 showed that survival differences between races can be explained by m o r e aggressive disease (larger t u m o r size and m o r e involved lymph nodes) within each stage a m o n g blacks. O t h e r investigators have f o u n d that African-American w o m e n are m o r e likely than whites to have m o r e biologically aggressive breast tumors, including a h i g h e r p r o p o r t i o n that are h o r m o n e receptor-negative, 2'1a'14 poorly differentiated, 2'11'15 high grade, 11'15 and have atypical nuclear features. ~°'15 R e c e n t investigations have shown that o t h e r potentially adverse prognostic indicators correlate with p o o r survival a m o n g African-American women, including nutritional markers, 11' 16 p53 g e n e alterations, ~7 and control of the cytochrome p450 enzyme system. 16 Whereas the bulk of evidence suggests that AfricanAmericans are diagnosed with a m o r e aggressive f o r m of breast cancer than are whites, we still d o n ' t know w h e t h e r these differences are mainly the result of endogS233
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T a b l e I. D i s t r i b u t i o n o f d e m o g r a p h i c a n d clinical characteristics by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d i n t h e D e t r o i t m e t r o p o l i t a n a r e a (1988-1992)
African-American Characteristic Age (yr) <50 50-64 65 + Marital status Married Widowed Divorced/separated Never married Unknown Census rank* Low Medium High Unknown Mammography history Done Not done Unknown
White
No.
%
No.
[
605 593 682
32.2 31.5 36.3
1917 2728 3977
22.2 31.6 46.1
727 418 279 348 108
38.7 22.2 14.8 18.5
5020 2134 664 663 141
58.2 24.8 7.7 7.7
1368 388 118 6
72.8 20.6 6.3
1274 3300 3964 84
14.8 38.3 45.9
858 131 891
86.7 13.2
4059 506 4057
88.9 11.1
I
%
<0.00001
<0.00001
<0.00001
0.149
*Census rank was categorized as low, medium or high, based on a composite of the percentage of persons over age 20 years who were high school graduates in that tract and the median household income for that census.
e n o u s factors o r w h e t h e r social o r s o c i o e c o n o m i c influe n c e s affect o u t c o m e . Several investigators have s t u d i e d the relationship between socioeconomic factors a n d survival.10,12, ls-27 Socioeconomic variables that have b e e n f o u n d to correlate with interracial survival differences include access to h e a l t h care or p a t i e n t delay in seeking treatment,10,12,18,19 social class (by census block group), 2°-22 education, 28 a n d income. 23'24 O t h e r investigators have shown that various o t h e r social a n d s o c i o e c o n o m i c att r i b u t e s s u c h as o c c u p a t i o n , z5 i n s u r a n c e status, 26 a n d characteristics o f t h e h o s p i t a l w h e r e t r e a t m e n t is received 27 c o r r e l a t e with b r e a s t c a n c e r survival. T h e o b j e c t i v e o f o u r analysis was to evaluate factors t h a t p r e d i c t survival differences b e t w e e n African-Americ a n a n d w h i t e w o m e n with b r e a s t c a n c e r in a n u r b a n c e n t e r with a large m i n o r i t y p o p u l a t i o n . W e were particularly i n t e r e s t e d in t h e i n f l u e n c e o f s o c i o e c o n o m i c status o n survival a n d w h e t h e r a n association existed b e t w e e n race a n d age.
Material and methods
Study eligibility. T h e study p o p u l a t i o n consisted o f b r e a s t c a n c e r cases d i a g n o s e d f r o m 1988 t h r o u g h 1992 a m o n g f e m a l e r e s i d e n t s o f m e t r o p o l i t a n D e t r o i t (Wayne, Oakland, and Macomb counties) and identified through t h e M e t r o p o l i t a n D e t r o i t C a n c e r Surveillance System (MDCSS).S Cases were selected f r o m 1988 t h r o u g h 1992 to best c o r r e l a t e with s o c i o e c o n o m i c d a t a d e r i v e d f r o m t h e 1990 census. Cases were a s c e r t a i n e d t h r o u g h t h e MDCSS, a f o u n d i n g m e m b e r o f t h e Surveillance, Epidemiology a n d E n d Results (SEER) p r o g r a m o f t h e Na-
tional C a n c e r Institute. x Eligible w o m e n were e i t h e r A f r i c a n - A m e r i c a n or white, h a d first p r i m a r y invasive b r e a s t cancer, a n d were alive at t h e t i m e o f diagnosis (i.e., cases a s c e r t a i n e d by d e a t h certificate a l o n e were e x c l u d e d ) . W o m e n with in situ b r e a s t c a n c e r were exc l u d e d b e c a u s e o f its p r e d i c t e d m i n i m a l i m p a c t o n b r e a s t c a n c e r survival rates, a n d w o m e n w h o h a d previously h a d p r i m a r y c a n c e r at any site ( e x c e p t n o n m e l a n o m a t o u s skin cancers) were e x c l u d e d b e c a u s e o f t h e p o t e n t i a l adverse affect o n survival rates. Variables. Data collection m e t h o d s u s e d at t h e MDCSS have b e e n d e s c r i b e d previously. 8 Variables evaluated i n c l u d e d d e m o g r a p h i c d a t a for t h e subjects, clinical i n f o r m a t i o n ( i n c l u d i n g first c o u r s e o f c a n c e r - d i r e c t e d t h e r a p y ) , a n d h o s p i t a l characteristics. D e m o g r a p h i c d a t a consisted o f age at diagnosis, race, m a r i t a l status, a n d a census-derived s o c i o e c o n o m i c r a n k (census r a n k ) t h a t was u s e d as a p r o x y for s o c i o e c o n o m i c status. C e n s u s rank, c a t e g o r i z e d as low, m e d i u m , o r h i g h , was c r e a t e d by c o m p i l i n g 1990 census d a t a for t h e p r o p o r t i o n o f h i g h s c h o o l g r a d u a t e s o l d e r t h a n age 20 years a n d m e d i a n h o u s e h o l d i n c o m e . 2°-22' 28 Clinical i n f o r m a t i o n i n c l u d e d past m a m m o g r a p h y use, t u m o r stage, t u m o r size, l y m p h n o d e status, histologic features, grade, a n d h o r m o n e ( e s t r o g e n a n d progestero n e ) r e c e p t o r stares. C o d i n g for m a m m o g r a p h y history was i n i t i a t e d i n 1990 a n d was classified as e i t h e r d o n e o r n o t d o n e . T u m o r staging (local, regional, or distant) was classified a c c o r d i n g to SEER guidelines, w h i c h have been d e s c r i b e d previously. 8 L y m p h n o d e i n v o l v e m e n t was c o d e d as e i t h e r n o involved n o d e s , axillary n o d e involve-
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Table II. Distribution of clinical characteristics by race a m o n g w o m e n with invasive breast cancer diagnosed in the Detroit m e t r o p o l i t a n area (1988-1992)
African-American Characteristic Tumor size T1 T2 T3 T4 Unlmown Lymph node status Zero Axi?[lary Disl~nt Unknown Stage Local Regional Remote Unknown Histologic type Invasive ductal Other Estrogen receptor* Positive Negative Unknown Progesterone receptor* Positive Negative Unknown Histologic grade One Two Three Four Unknown
No.
White No.
%
p
789 698 187 22 184
46.5 41.2 11.0 1.3
4933 2505 420 54 710
62.3 31.7 5.3 0.7
909 723 19 229
55,1 43.8 1.1
5073 2754 50 745
64.4 35.0 0.6
1007 719 119 35
53.6 38.2 6.3
5401 2858 293 70
62.7 33.1 3,4
<.00001
1304 576
69.4 30.6
6053 2569
70.2 29,8
0.49
535 343 1012
60.9 39.1
3185 850 4587
78,9 21.1
<0.00001
467 403 1010
53.7 46.3
2690 1261 4671
68.1 31,9
<0.00001
59 288 510 51 972
3.2 15.3 27.1 2.7 51.7
368 1245 1427 129 5473
4.3 14.4 16.6 1.5 63.2
0.00001
<0.00001
<0.00001
*Hormone receptor values were only available for women diagnosed in 1990 or later. The positive category included the cases that were categorized as positive or borderline. ment, or distant n o d e involvement (including internal m a m m a r J nodes and o t h e r distant sites). Estrogen and p r o g e s t e r o n e r e c e p t o r status were classified as either positive (including those that were borderline) or negative. R e c o r d of h o r m o n e r e c e p t o r results were kept only f r o m 1990 forward. I n f o r m a t i o n on cancer-directed therapy i n c l u d e d data on the primary surgery, radiation therapy, c h e m o t h e r apy, and h o r m o n a l therapy. Surgical p r o c e d u r e codes i n c l u d e d partial mastectomy (with or without axillary lymph n o d e dissection), simple mastectomy (without dissection of axillary lymph nodes), m o d i f i e d radical mastectomy, radical mastectomy, and o t h e r (including subcutaneous mastectomy or surgery to o t h e r or distant sites). Primary radiotherapy was delivered postoperatively to the affected breast, and c h e m o t h e r a p y and h o r m o n a l therapy were based on initial and follow-up abstracts. No detailed data were available r e g a r d i n g therapeutic dosage, duration, or exact p o r t of t r e a t m e n t for radiation. I n f o r m a t i o n on hospital characteristics p e r t a i n e d to the institution at which the patient received h e r first
course of cancer-related therapy. If the subject was treated at m o r e than one hospital, priority was given to the hospital where it was estimated that the w o m a n would be most likely to have o n g o i n g care for breast cancer (i.e., the hospital where the definitive breast surgery occurred, a larger hospital, or a hospital with a residency training p r o g r a m ) . Hospitals were categorized by n u m b e r of beds and residency training status according to guidelines in the A m e r i c a n Hospital Association Guide to the Health Care Field. 29 I n f o r m a t i o n on the p r o p o r t i o n of Medicare a n d / o r Medicaid patients discharged f r o m each hospital was used t o estimate subject insurance status. These data were o b t a i n e d from the SEER Patterns of Care Study and were originally used by the H e a l t h Care Financing Administration to d e t e r m i n e r e i m b u r s e m e n t on the basis o f hospital discharges. 3° A hospital with a h i g h e r p r o p o r t i o n of Medicaid a n d / o r Medicare discharges is assigned a h i g h e r n u m b e r on a 1 to 9 scale. Design and analysis. T h e primary o u t c o m e variable was overall survival ( m e a s u r e d in m o n t h s ) , which was the
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T a b l e III, D i s t r i b u t i o n o f t r e a t m e n t m o d a l i t i e s by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d in t h e D e t r o i t m e t r o p o l i t a n a r e a (1988-1992
African-American Characteristic Surgery Partial mastectomy* Simple mastectomy Modified radical mastectomy Radical mastectomy Other t Unknown Chemotherapy + Yes No Radiation therapy + Yes No Hormonal therapy + Yes No
No.
]
White
%
No.
536 75 1201 5 15 48
29.3 4.1 65.5 0.3 0.8
2811 259 5094 18 35 405
34.2 3.2 62.0 0.2 0.4
0.00007
499 1381
26.5 73.5
1732 6890
20.1 79.9
<0.0000l
522 1358
27.8 72.2
2495 6127
28.9 71.1
0.309
428 1452
22.8 77.2
1808 6814
21.0 79.0
0.085
*The partial mastectomy category includes those with or without axillary lymph node resection and subcutaneous mastectomy. t T h e "other" category includes subcutaneous mastectomy or surgery for regional or distant disease. ~No detailed information was included in the SEER database regarding therapeutic dosage, duration, or exact port of treatment for radiation. T a b l e IV. D i s t r i b u t i o n o f h o s p i t a l variables by race a m o n g w o m e n with invasive b r e a s t c a n c e r d i a g n o s e d in t h e D e t r o i t m e t r o p o l i t a n area (1988-1992)
African-American Characteristic Hospital size (No. beds) <200 >200 Residency training No Yes Proportion of Medicaid a n d / o r Medicare discharges* 1 2 3 4 5+
White
No.
%
No.
%
P
156 1724
8.3 91.7
1447 7175
16.8 83.2
<0.00001
420 1460
22.3 77.7
2808 5814
32.6 67.4
<0.00001
261 335 340 565 379
13.9 17.8 18.1 30.1 20.1
5273 1772 969 496 112
61.2 20,6 11,2 5.8 1.3
<0.00001
*This information was derived by the Health Care Financing Administration and used for the SEER Patterns of Care study. 3° A hospital with a higher proportion of Medicaid a n d / o r Medicare discharges is assigned a higher number on a 1 to 9 scale. interval b e t w e e n date o f diagnosis a n d date o f last activity or d e a t h f r o m any cause. M e t h o d s u s e d by t h e MDCSS to ascertain follow-up have b e e n d e s c r i b e d previously. 3 Overall survival rates r a t h e r t h a n b r e a s t c a n c e r - s p e c i f i c survival rates were u s e d as a n o u t c o m e b e c a u s e o f e x p e c t e d i n c o n s i s t e n t r e p o r t i n g o n t h e basis o f d e a t h certificates. T h i s m e t h o d o f a s c e r t a i n i n g survival h a s b e e n u s e d by o t h e r s a n d has b e e n f o u n d to show c o m p a r a b l e results to analyses t h a t use b r e a s t c a n c e r specific survival rates, u U n i v a r i a t e analyses were u s e d to assess differences b e t w e e n p o t e n t i a l c o n f o u n d i n g variables a n d race (Tables I, II, III, a n d IV). 31 Cox p r o p o r t i o n a l h a z a r d s
r e g r e s s i o n was u s e d to e s t i m a t e t h e relative risk o f d e a t h f r o m any cause in A f r i c a n - A m e r i c a n w o m e n c o m p a r e d with white w o m e n as d e s c r i b e d previously. 3' 3z I n f o r m a tion o n past use o f m a m l n o g r a p h y a n d h o r m o n e receptor status were n o t i n c l u d e d in t h e Cox m o d e l b e c a u s e data were available only for w o m e n d i a g n o s e d b e g i n n i n g in 1990. Axillary l y m p h n o d e status was also n o t u s e d in the model because detailed information on the number o f involved axillary l y m p h n o d e s was n o t available a n d it was e x p e c t e d t h a t a h i g h d e g r e e o f colinearity w o u l d exist b e t w e e n axillary l y m p h n o d e status a n d t u m o r stage. Data o n c a n c e r t h e r a p y f r o m t h e SEER registry were c o n s i d e r e d i n c o m p l e t e b e c a u s e m o s t c h e m o t h e r -
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apy and h o r m o n a l therapy administered for breast cancer are given on an outpatient basis, usually at a private office, and thus these data were n o t i n c l u d e d in the multivariate model. Potential interactions between race and o t h e r indep e n d e n t variables (age g r o u p and hospital size) were assessed and the statistical significance of interaction terms were evaluated with use of likelihood ratio tests. T h e appropriateness of the p r o p o r t i o n a l hazards ass u m p t i o n was assessed with use of the Breslow-Day test for the h o m o g e n e i t y of relative risks, which showed p r o p o r t i o n a l hazards t h r o u g h 48 m o n t h s after diagnosis. 3a T h e r e f o r e all analyses using Cox p r o p o r t i o n a l hazards models refer to events o c c u r r i n g up t h r o u g h 48 months.
Results F r o m 1988 t h r o u g h 1992, a total of 10,715 newly diagnosed cases of invasive breast cancer were identified in the Detroit m e t r o p o l i t a n area. T h e analyses r e p o r t e d h e r e include only the cases that were diagnosed a m o n g white (82%) or African-American (18%) w o m e n and excluded w o m e n who were of a n o t h e r or u n k n o w n racial category (n = 213). Table I lists d e m o g r a p h i c characteristics of the study cohort. African-American w o m e n were significantly m o r e likely than white w o m e n to be young, single, and to reside in a census tract that had a low s o c i o e c o n o m i c rank. No a p p a r e n t differences existed by race for aast m a m m o g r a p h y use. Table II lists the distribution of clinical characteristics by race. African-American w o m e n were m o r e likely than white w o m e n to have m o r e aggressive disease as n o t e d by m o r e advanced stage at diagnosis (i.e., larger tumors and a h i g h e r p r o p o r t i o n with axillary n o d e - p o s i t i v e tumors), tumors of a h i g h e r grade, and m o r e tumors that were h o r m o n e r e c e p t o r - n e g a t i v e . No differences in histologic t u m o r type (invasive ductal versus other) were f o u n d by race. Table III lists the use of cancer-directed t r e a t m e n t by race. African-Americans were less likely to have a partial mastectomy (with or without axillary lymph n o d e dissection) than were whites. African-Americans were aiso m o r e likely to have received c h e m o t h e r a p y than were whites. No statistically significant differences in t r e a t m e n t with radiation therapy or h o r m o n a l therapy were f o u n d by race. As indicated in Table IV, AfricanA m e r i c a n w o m e n were m o r e likely to be diagnosed or to receive their primary therapy at larger hospitals, as well as hospitals that had residency training programs. Hospitals at which African-American w o m e n were treated were also m o r e likely to have treated (discharged) a larger p r o p o r t i o n of patients who had e n t i t l e m e n t insurance (Medicare a n d / o r Medicaid) than did hospitals at which white w o m e n were treated. An evaluation of Kaplan-Meier survival curves for African-American and white w o m e n with breast cancer
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Table V. Results of age-specific models of the risk of death a m o n g blacks and whites /
Characteristic
Age <50 yr Unadjusted Race (black vs. white) Multivariate adjusted* Race (black vs. white) Age ->50 yr Unadjusted Race (black vs. white) Multivariate adjusted* Race (black vs. white)
Relative | 95 % Confidence risk .1 inlerual
2.35
1.88-2.93
1.68
1.27-2.23
1.66
1.46-1.88
1.33
1.13-1.56
*Multivariate models adjusted for age, tumor size, stage, histologic grade, census rank, and residency" training. stratified by stage showed that survival rates were significantly better for white w o m e n with local and regional stage disease (log rank p = 0.0001). No statistically significant differences in survival rates for African-American and white w o m e n with r e m o t e stage disease were f o u n d (log rank p = 0.3) (data n o t shown).a Multivariate m o d e l i n g showed a significant interaction between age group ( < 5 0 years vs. ---50 years) and race (p = 0.005) (Table V). Each m o d e l provides the unadjusted relative risk of death a m o n g African-American w o m e n c o m p a r e d with white w o m e n and the adjusted relative risk controlling for age, t u m o r size, stage, histologic grade, census rank, and the presence of a residency training p r o g r a m at the t r e a t m e n t hospital. T h e relative risks o f dying for young African-American w o m e n was greater than those for older African-American w o m e n (adjusted relative risk 1.68 versus 1.33, respectively). A d j u s t m e n t for marital status, the n u m b e r of beds in the hospital, and the p r o p o r t i o n of patients discharged who received Medicaid or Medicare benefits had n o further impact on mortality differences between African-American w o m e n and white women. No significant differences in survival for African-American or white w o m e n who lived b e y o n d 48 m o n t h s after the cancer was diagnosed were found.
Comment O u r results c o n c u r with findings of o t h e r reports that show a substantially worse mortality e x p e r i e n c e a m o n g African-American w o m e n with breast cancer c o m p a r e d with white women. 4-a' 9, xl, 13 To date a completely satisfactory explanation for these mortality trends has n o t b e e n found, although n u m e r o u s investigations reveal a n u m b e r of potentially interesting explanatory variables including b o t h social or s o c i o e c o n o m i c < 10, 1~-20,22-25 and biologic influences. 5' 8-H, 13, 17 It is possible that socioecon o m i c differences between African-American and white w o m e n are manifested as differences i n the biologic nature of the tumors, which results in a p o o r e r overall o u t c o m e for African-American women. O n e e x a m p l e of
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this hypothesis is t h e r e l a t i o n s h i p b e t w e e n dietary habits i n f l u e n c e d by c u l t u r a l n o r m s a n d b r e a s t c a n c e r survival differences b e t w e e n A f r i c a n - A m e r i c a n a n d w h i t e women. 5 I n o u r analysis we were u n a b l e tq evaluate several p o t e n t i a l e x p l a n a t o r y variables for b r e a s t c a n c e r survival rates b e c a u s e o f limitations in t h e SEER data. S o m e investigators have s u g g e s t e d t h a t issues r e l a t e d to access to h e a l t h care 18 a n d p a t i e n t delay i n s e e k i n g treatmentl0, 19 m a y have a n adverse i m p a c t o n stage o f disease at t h e t i m e o f diagnosis. I n fact, several investigators have s u g g e s t e d t h a t race itself h a s a m i n i m a l role i n d e t e r m i n ing b r e a s t c a n c e r survival rates after a d j u s t m e n t for disparities in i n c o m e 2~'25 a n d e d u c a t i o n . 23 However, racial differences in rates o f b r e a s t c a n c e r survival cont i n u e to b e a m a j o r p r o b l e m affecting t h e AfricanA m e r i c a n c o m m u n i t y a n d s h o u l d c o n t i n u e to b e a focus in f u t u r e h e a l t h care p l a n n i n g efforts. 22 A f r i c a n - A m e r i c a n w o m e n with b r e a s t c a n c e r in o u r study p o p u l a t i o n were m o r e likely t h a n white w o m e n to reside in a n a r e a with a low s o c i o e c o n o m i c level, to b e h o s p i t a l i z e d at a n i n s t i t u t i o n t h a t p r o v i d e s a h i g h prop o r t i o n o f care for t h e i n d i g e n t , a n d to have a d v a n c e d stage t u m o r s a n d aggressive t u m o r s (i.e., a h i g h e r prop o r t i o n with h o r m o n e r e c e p t o r negativity at diagnosis). A l t h o u g h i n f o r m a t i o n o n c a n c e r t r e a t m e n t in t h e SEER registry is n o t c o m p l e t e , o u r d a t a d e m o n s t r a t e d t h a t A f r i c a n - A m e r i c a n w o m e n r e c e i v e d t h e s a m e or m o r e aggressive c a n c e r - r e l a t e d t r e a t m e n t t h a n d i d white women. O u r results i n d i c a t e d t h a t survival differences b e t w e e n A f r i c a n - A m e r i c a n a n d white w o m e n are especially i m p o r t a n t for w o m e n in t h e first 4 years after diagnosis, in t h o s e with early stage disease, a n d for w o m e n in w h o m t h e c a n c e r was d i a g n o s e d w h e n they were less t h a n 50 years o f age. Interestingly, o u r f i n d i n g s r e v e a l e d t h a t A f r i c a n - A m e r i c a n w o m e n w h o survive l o n g e r t h a n 48 m o n t h s have survival rates similar to t h o s e o f white w o m e n . F u r t h e r analyses o f l o n g - t e r m survival rates a m o n g A f r i c a n - A m e r i c a n w o m e n m a y p r o v i d e i n s i g h t as to t h e factors t h a t m i g h t p r e d i c t i m p r o v e d survival rates for all A f r i c a n - A m e r i c a n w o m e n with b r e a s t cancer. The larger impact on mortality seen among young A f r i c a n - A m e r i c a n w o m e n m a y b e t h e r e s u l t o f different social a n d o r c u l t u r a l i n f l u e n c e s t h a t affect y o u n g e r women more than older women. These findings indicate t h e n e e d to focus m o r e a t t e n t i o n o n p u b l i c h e a l t h efforts for y o u n g e r w o m e n to achieve a large i m p a c t o n racial differences in b r e a s t c a n c e r survival rates. T h e s e efforts s h o u l d i n c l u d e i m p r o v e m e n t in c o m m u n i t y e d u c a t i o n a b o u t t h e i m p o r t a n c e o f early d e t e c t i o n ( a n d t h e fact t h a t b r e a s t c a n c e r c a n b e c u r e d if d e t e c t e d early), i m p r o v e m e n t in access to s c r e e n i n g m a m m o g r a m s , a n d b r o a d e n i n g o f s u p p o r t for n e w a n d existing b r e a s t can-
June ]997 Am J Obstet Gynecol
cer p r e v e n t i o n trials t h a t i n c l u d e all c o m m u n i t i e s o f women.
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