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RESULTS
A) An overview on racial disparities:
This study presented an overview on racial disparities in the survival outcome of patients with
twenty three of the most common primary-site cancers in the US. Data about these patients were
adopted from three cohorts representing three successive decades. A collective analysis of the data of
these patients showed significantly lower survival probabilities for black than white patients over the
three studied decades. However, analysis of the data for each cancer site separately showed that there
was no statistically significant difference in the survival outcome between the black and the white
patients in the majority of the studied cancers. Only female breast cancer, prostate, urinary bladder,
colorectal and uterine cancers demonstrated statistically significant survival disparities which were
consistent in the three studied cohorts (figure 1 ).
Fig 1.
B) Racial disparities in breast cancer survival:
Breast cancer in females was selected to study the possible causes for the persistent survival
disparities between the black and the white cancer patients in the studied cohorts. The one, three, five,
and ten-year survival fractions remained lower in the black than the white patients over the three studied
decades (table
). Figure
shows that considerable advances in the survival outcome have been
achieved for both of the black and the white breast cancer patients in the last three decades; however, the
survival gap between them did not disappear and the difference in the survival probability remained
roughly constant.
Survival rate in black patients was permanently lower than that of white patients regardless of
the age of patient at diagnosis, stage and grade of the breast cancer at the time of diagnosis, and was
independent from the operability of the diagnosed cancer and the status of radiation treatment of these
patients (whether radiation was given or not). The survival disparities between the two ethnic groups
persisted even after adjustment for each of the previous factors individually (figures
to
).
Black patients were diagnosed at earlier age than white (the mean age difference was 3.5-4
years). The majority of both of the black and white patients were married and/ or previously married
(whether separated or legally divorced). The rate of single females who had cancer breast was nonsignificantly higher in black than the white female patients.
For patients with localized breast cancers, the percentage of the white patients was significantly
higher than the black. However, black patients had a significantly higher probability to be diagnosed
with the regional and distant breast cancers than whites. This means that black patients tend to be
diagnosed at higher and more invasive stages than whites. Moreover, black patients were mostly
diagnosed with less differentiated cancers. These results were consistent whether the data for the three
cohorts were collectively or separately analyzed for each of these cohorts.
Although they were diagnosed at more invasive stages and with more serious and less
differentiated cancers, black patients showed a lower rate of undergoing surgery in the three studied
cohorts. This effect could not be attributed to lack of access to the surgical facilities, inoperability of
their cancers, or that surgery was not being recommended by the health team. Analysis of SEER breast
cancer patients who had access to surgical facilities and for whom surgery was recommended after
diagnosis showed that black patients were less inclined to undergo surgery than the white patients.
Additionally, black patients mostly die due to breast cancer or the treatment consequences; however the
white patients mostly die due to causes of death other than the cancer itself.
Adjustment for the age, marital status, laterality of the cancer, stage, grade, and treatment
variables (undergoing surgical and radiation regimens) was done with the Cox regression analysis. After
adjustment for these factors simultaneously, the probability of survival of a black patient at last contact
become approximately equal to that of the white population (odds ratio = 1.02). Stage and grade of
cancer at diagnosis, and performance of surgical excision of the tumor appeared as significant
independent predictors of the survival status.
DISCUSSION
In this study, the existence of racial disparities in the survival of patients with 23 primary-site
cancers was assessed. The status of these disparities over time was mitigated by analysis of the SEER
survival data of patients with these cancers over three cohorts chosen from three successive decades. To
avoid the effect of the gender disparities, the survival data were analyzed and presented for each sex
separately. To the maximum of our knowledge, no previous comparative studies have presented such a
panoramic overview of the patients’ survival data from many cancer sites, cohorts, and in both sexes in
order to investigate the presence of survival racial disparities.
Analysis of the survival data from all cancer sites combined showed a significantly lower
survival for the black than the white cancer patients. Individual analysis of the data from each cancer site
showed that, in the majority of the studied cancers, black patients had lower survival probabilities than
the white, but this difference was non statistically significant and was not consistent over decades. Only
few cancers demonstrated a statistically significant survival difference between the two racial groups
which was persistent throughout the three cohorts. These were breast cancer in females, urinary bladder,
prostatic, uterine, and colorectal cancers. Consequently, the overall observed cancer survival disparities
in the U.S could be due to the disparities in few, but highly prevalent, cancers rather than real racial
disparities for patients with all cancer types. To know why these cancers in particular showed these
significant differences, a more detailed and individualized analysis is needed in which the cancerspecific factors, patient factors and treatment variables are considered. With exclusion of breast cancer,
the other cancers with evident racial disparities will be handled in later publications.
Breast cancer in females was selected as example to study the possible factors which lie behind
racial disparities of the survival outcome. The reasoning of this selection is that breast cancer is the most
incident cancer in the U.S1, it has shown the largest difference in survival between the black and the
white patients, and this difference remained constant over the three cohorts. Survival data of female
breast cancer patients were only considered because of the high incidence of this cancer in females in a
way that warrant the presence of sufficient number of cases for analysis in all age groups, in addition to
avoidance of the bias that may happen by the gender-based causes of health disparities.
Analysis of the data of the breast cancer patients showed that black patients had a significantly
lower age at diagnosis than white. Similarly, Cunningham and Butler2 reported that African American
women had significantly lower age at diagnosis with breast cancer than did European American women.
Theoretically, this fact might be explained by better screening and diagnosis of black than white
patients. However, this assumption seems implausible as the previous literature demonstrated that black
patients are more likely to be disadvantaged in the screening and diagnosis than white3-5.
More
practically, this conclusion may be attributed to the earlier age of incidence of breast cancer in black or
that blacks may suffer more aggressive cancers than whites for certain biological reasons.
Although they were diagnosed four years earlier than white, black women were diagnosed at
more invasive stages and with less differentiated cancers throughout the three studied cohorts. A study
on South Carolina breast cancer patients confirmed these results and argued that black women tend to be
diagnosed with estrogen-negative progesterone negative tumors which are less likely to be
mammographically detected; hence they will be discovered clinically at higher cancer stages2.
Moreover, screening mammograms are less effective in premenopausal women due to greater
mammographic density, that is why black women who are diagnosed at younger ages than white and
have more voluminous breasts are more likely to be diagnosed by themselves or by physician rather than
by mammography6. Evidently, when the breast cancer becomes clinically palpable, it is expected to be
of larger size and at more invasive stage. Some other studies proved that black women have, on average,
breast cancer of more aggressive histopathology and tend to show nodal involvement at younger ages
than were white women7,8.
Adjustment for the age, marital status, laterality of the cancer, stage, grade, and treatment
variables (undergoing surgical and radiation regimens) was done with the Cox regression analysis. After
adjustment for these factors, the probability of survival of a black patient at last contact become
approximately equal to that of the white population (odds ratio = 1.02). Stage and grade of cancer at
diagnosis, and performance of surgical excision of the tumor appeared as significant predictors of the
survival status.
Discussion of the racial differences in breast cancer incidence and mortality is puzzling.
According to the SEER data, African-American women (AA) have a 23 % higher death rate from breast
cancer than do women of European descent (EA) (102.0 versus 83.1 deaths per 100,000 women, ageadjusted to the 2000 US population, for years 1996-2000), and yet have a 15 % lower incidence rate
(120.8 versus 142.0 per 100,000 women)9. Over the last thirty years, breast cancer mortality rate for EA
women have declined by about 15% but risen 22% for AA women10. This study showed that white
females had better survival than black and were more likely to die from causes other than breast cancer;
however black patients mostly die due to breast cancer or cancer treatment sequale.
Despite the considerable advances in survival that have been achieved over the last 30 years for
the two races (figure
), black women persisted to show lower survival probability than white at the
one, three and five years post diagnosis in the studied cohorts, and a lower ten-year survival fraction in
the 1979-1983 and 1989-1993 cohorts (table ). There was no sufficient time span for the 1999-2003 to
study the ten-year survival probability. Several explanations could be discussed on this regard. The most
commonly argued of them is that black women had poorer access to the health system and a lower
health insurance coverage rate. Other factors, which may be less discussed, are lack of access to proper
screening programs, inequalities in management and referrals within the health care system, lower
socioeconomic level of black women, and presence of communication problems that affects the ability
of the patient and the health team to co-design a well-planned treatment regimen. In the literature about
breast cancer, the role of cell biology and genetic predispositions in breast cancer racial survival
disparities were rarely discussed. In fact, nothing of these factors could be indefinitely ruled out, because
these factors may act individually, in part, or altogether to sum up the resulting disparities. These factors
can be discussed in the light of our results as well as the previous literature on breast cancer racial
disparities in order to highlight the most influential factor in development of these survival disparities.
Lack of access to health care facilities and insufficient or inefficient screening programs for
black women may be a cause for these disparities. It is explicitly known that presence of such factors
will delay diagnosis resulting in more advanced-stage cancer, with more chance for distant spread, lag in
the treatment initiation and poor survival outcome11. Results of this study demonstrated that black
women are diagnosed at earlier age than did the white, but with higher staged cancer. Further analysis of
the data of patients within each stage and grade of cancer separately, showed that survival disparities
continued to show up, even after adjustment for the stage and grade of cancer at diagnosis. Additionally,
analysis of the survival data of patients who underwent surgery (which means that they had access to
surgical facilities and are covered by insurance), showed lower survival in black than white patients.
This suggests that lack of access to health care and screening programs is not a conclusive explanation
for these racial survival disparities.
Lack of efficient screening in black could be explained biologically by the high prevalence of the
ER-ve PR-ve breast tumors in black women which are hardly identified by mammography2. A study on
the early breast cancer Medicaid beneficiaries who had the same cancer staging, similar socioeconomic
standard, health care access, and received similar treatment regimens found that black patients had lower
survival probability than whites, and suggested that factors other than health care access, SES, and
treatment differences may contribute to the racial disparity in survival12. In our study, black patients who
were diagnosed in very early stages (stages I and II) remained to show lower survival than white females
of the same stages. This denotes that using screening tools for early diagnosis, although very important,
but it is not the key factor in causation of the observed survival differences.
Inequality in the management and referrals of patients, if present, might be a cause for racial
disparity in survival. However, it is not expected that the medical team will discriminate in the medical
decisions needed for diagnosis and treatment on a racial basis, as it is beyond the medical ethics and is
criminalized by the Acts of Law of the medical practice. Even if present, it could provide explanation
for lower survival in a few number of cases but never to explain the matter of racial survival disparity
that is consistent across the nation and persistent over decades. Also, if the discrimination within the
health system was assumed, this does not explain why most of the studied cancers did not show
significant racial disparities in survival, while only five cancers did. Moreover, It is non logical that the
medical efforts which resulted in evident improvements in cancer survival for the two races over the last
three decades, as was proved in this study (figure
), were always lie short for the blacks to maintain a
survival gap between the blacks and the whites. If there is any role for the medical team in the health
disparities, it could be a communication problem with the patients due to language, social or religious
barriers that reduce the responsiveness of the black patients to the diagnostic and treatment
recommendations of the health team.
These results suggested a biological evidence of racial disparity in cancer survival. A persistent
survival gap between the blacks and the whites was identified over the three studied cohorts; this gap did
not disappear in spite of the marked advances in the cancer survival outcome of the two racial groups, as
identified by the dramatic shift of the survival plots from the left to the right over the successive
decades. The lower survival in the black women persisted irrespective of the availability of access to
health care, the stage and grade of cancer, surgical status, and whether radiation was given or not
(figures
to
). Also, Black patients may be genetically or biologically susceptible to develop breast
cancer at earlier age and may develop more aggressive tumors. The earlier age of diagnosis in blacks
could be due to early breast cancer incidence in blacks or due to the more aggressive tumors in blacks
which become clinically manifested at earlier age. Black patients were more susceptible than whites to
develop ductal carcinomas which are highly invasive, while the less invasive lobular carcinomas are
more incident among whites2,13.
Furthermore, this study demonstrated that black patients were significantly more likely to be
diagnosed with regional and distant cancers of low-differentiated or undifferentiated pathological
grades, on contrary to the white patients who are mostly diagnosed with localized and welldifferentiated cancers. Also, The higher incidence of the ER-ve PR-ve tumors which are less screenable
and of more aggressive nature provides another clue from the literature that supports the possibility of
biological reasons for the racial disparities in survival of the breast cancer patients14,15.
It was presented earlier in this study that black patients had significantly lower survival than
whites in few cancers only; however the majority of the studied cancers did not show this significant
survival difference. This result favors that the lower survival in black patients were not exclusively due
to lack of access to health care, lack of coverage by health insurance, discrimination in diagnosis and
treatment, or socicoeconomic differences; otherwise these factors should have resulted in lower survival
probabilities for black in all of the studied cancers. This conclusion suggests that certain organ-specific
biological and genetic factors lie behind the survival differences between the two races.
A limitation of this study is the SEER classification for the cause of death which was entirely
based on death certificates or autopsy reports. It is not uncommon that the cause of death is inaccurately
reported in the death certificate as “death due to circulatory failure” “or old age”. If a misclassification
bias had happened in the reporting of the cause of death to the SEER database, this may subsequently
affect the survival models we presented in this study. Also, the race classification in the SEER database
was obtained from databases of the hospitals which entirely depend on patients’ self-reporting, hence
inaccurate reporting of the racial and ethnic background to the SEER database, whether due to patient
ignorance or hospital negligence, may result in a misclassification bias in this study. In some instances
cause-specific survival may be inaccurate. For example, cause of death may be unreliable or unknown or
if a cancer has metastasized to another site, the death certificate may list cancer of the metastasized site
as the cause of death. To eliminate these limitations, only individuals with one primary cancer were
included in the cohort and if the cause of death is missing the cases were excluded from the analysis.
No information about the personal information of the patients or their social security numbers is
available in the SEER database. Although this is an advantage from the security and privacy
perspectives, but it has limited our ability to get information about patients’ insurance benefits, medical
facilities involved in the diagnosis and treatment, and patients’ socioeconomic status…etc. These data
would have been important to include in our analysis in order to implement a comprehensive
multivariate regression analyses on the factors which may result in the observed disparities.
Otherwise, this study provided several strengths as it is the first study to demonstrate the age and
race- dependent survival of many types of cancer, in both genders, and over three different cohorts. One
of the advantages is that we adopted our data from the SEER database which is the U.S. largest and most
accurate database in which all of the minorities and ethnic subgroups are represented. This is the first
study to provide detailed survival graphs for patients of 85+ years, as divided into 5- year age groups up
to the age of 115. Furthermore, breast cancer in females was selected to investigate the possible factors
which control the survival outcome in both of the black and the white patients and may have resulted in
the racial survival disparities. Many variables were included in the analysis including personal,
diagnostic, pathological, and treatment data of the selected patients. Survival probabilities for the two
races were analyzed in each of the cancer stages, grades, and treatment methods separately to study the
effect of change of these variables on the survival gap between the studied races.
In conclusion, this study did find that the racial differences in survival were not significant in all
cancers, but rather appear in some of the widely prevalent cancers. Although this study did not definitely
exclude the effect of health care and insurance inaccessibility, discrimination in diagnosis and treatment,
and other social factors in formulation of the survival differences between the studied races of breast
cancer patients, however; it highlighted the possibility of existence of unfavorable biological factors in
the black patients which determine the age of patient at cancer incidence and diagnosis, as well as cancer
type, stage at diagnosis, cellular differentiation, and aggression of the cancer which eventually lead to
the lower survival probability in blacks.
Acknowledgment
Dr. Bassily acknowledges the grant awarded to him by Exergen Corporation, of Watertown, MA
in support for this research study.
Conflicts of interest
Authors declare that no conflicts of interest pertinent to the topic of this study are to be disclosed.
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