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Racial disparities in blacks with gynecologic cancers
Article first published online: 8 JUN 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 2, pages 234–243, 15 July 2007
How to Cite
Farley, J., Risinger, J. I., Rose, G. S. and Maxwell, G. L. (2007), Racial disparities in blacks with gynecologic cancers. Cancer, 110: 234–243. doi: 10.1002/cncr.22797
- Issue published online: 29 JUN 2007
- Article first published online: 8 JUN 2007
- Manuscript Accepted: 28 FEB 2007
- Manuscript Revised: 22 FEB 2007
- Manuscript Received: 6 FEB 2007
Black women have a lower incidence of gynecologic cancers but they have a higher mortality associated with their disease. The etiology of the racial disparity in outcome among gynecologic cancer patients is multifactoral and site-specific. Black women with endometrial cancer often present with more advanced stage tumors that are associated with a worse prognosis compared with White women. Evidence suggests that observed disparities in outcome are due to inequalities in treatment or differing biologic etiologies. For cervix cancer, studies have suggested that survival among Black women may be lower than survival among White women that develop this disease. This occurs despite evidence that indicates that Pap smears are utilized similarly by Black and White women for cervix cancer screening. These differences in outcome may become less pronounced when comorbidities are accounted for and inequalities in treatment are eliminated. For ovarian cancer patients, survival has improved with the use of contemporary therapies over the past 30 years in Whites but less so for Blacks. This may be due to differences in the likelihood of primary surgical cytoreductions, which are performed less frequently in some Black women because of extensive metastatic spread or comorbidities. The observed decreases in survival for all 3 gynecologic cancers potentially may be affected by socioeconomic status of the patient in some healthcare settings. An improved understanding of the causative factors associated with racial disparities in gynecologic cancer outcome is necessary to facilitate efforts aimed at correcting this important healthcare problem. Cancer 2007. © 2007 American Cancer Society.
In the US, approximately 140,000 new cases of cancer will be diagnosed annually in Black patients, 6400 of which will be of gynecologic origin. Survival in black women with gynecologic cancers is worse compared with White women and the etiology of this racial disparity in outcome is not well understood. Identification of underlying etiologic factors is important in order to facilitate implementation of corrective measures aimed at minimizing the risk of cancer-related disparities among gynecologic cancer patients. The following review summarizes some of the issues related to each gynecologic cancer site in the context of racial disparities in incidence and outcome.
According to the Surveillance, Epidemiology, and End Results (SEER) program, the incidence of endometrial cancer among Blacks is 33% lower than in Whites.1 However, the mortality among Blacks with endometrial cancer is 80% higher than in Whites, resulting in almost 1000 deaths annually.1 Although only 7% of newly diagnosed patients are Black, approximately 14% of deaths related to endometrial cancer will occur in Blacks.2 Incidence rates for endometrial cancer are determined using population-based estimates that include patients that have had a hysterectomy. The lower incidence of endometrial cancer among Blacks may in part reflect a higher prevalence of hysterectomy for benign gynecologic disease in minority patients and women with low socioeconomic status (SES).3 Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial cancer risk, particularly among Blacks.4 Minimally invasive surgical alternatives to hysterectomy may potentially lead to higher observed rates of endometrial cancer, particularly among groups that have traditionally had definitive surgical therapy for benign gynecologic problems.3
For some illnesses the interval between the onset of symptoms and the acquisition of care may be affected by either access to care or cultural and social dynamics that influence the patients seeking medical attention. In an assessment of 219 patients that underwent surgical staging for endometrial cancer, investigators evaluated racial differences in the interval between the onset of symptoms and the performance of the hysterectomy. In this group of patients the median interval was similar between Blacks and Whites (11.1 weeks and 13.7 weeks, respectively). Investigators also found that women in this study using hormone replacement therapy were more likely to have a prolonged interval between onset of symptoms and definitive surgery. Because Black women were less likely to use hormones, the Black women in this study would have been biased to seek medical attention sooner. Multivariate regression of endometrial cancer survival in these patients found that a racial disparity in multiple clinicopathologic factors exists even after controlling for hormone use.5
In Black patients with a low SES a lack of insurance or financial resources may either influence a poor patient from seeking care or affect access to care within some healthcare systems. These economic barriers have the potential to delay access to care, resulting in patients presenting with more advanced disease. In 1 multivariate analysis, women with a low SES can also be associated with a higher likelihood of advanced stage disease at the time of diagnosis. Black women were 41% more likely to present with advanced stage disease even after accounting for tumor grade, histology, and age. SES and race were found to be collinear in regression analysis, prohibiting an accurate determination of the independent contributions of each variable to advanced stage disease. Subsequent analysis has revealed that among patients with ‘aggressive’ tumor histology (ie, clear cell, serous, and undifferentiated), age, race, and median family income were not associated with advanced stage at diagnosis. However, among patients with ‘favorable’ tumor histology (endometrioid and mucinous), either SES or race (but not both) were associated with advanced stage disease in a multivariate model. These findings suggest that improvements in access to care may benefit Black patients and financially disadvantaged women with endometrial cancer, particularly those that develop tumors with more ‘favorable’ histology. Patients with ‘aggressive’ tumors may be more likely to have advanced stage at the time of diagnosis irrespective of race or SES.6
Comorbidities such as obesity-related diseases are increased among Blacks compared with Whites,7 which potentially can lead to an increased risk of developing endometrial cancer and a decreased likelihood of overall survival. The prevalence of obesity among Blacks has grown to epidemic proportions, with approximately 77% of Black women being classified as overweight (body mass index [BMI] ≥25) and 50% (BMI ≥30) designated as obese.8 In a case-control study of over 62,000 women from the Netherlands Cohort Study on Diet and Cancer, women with a BMI ≥30 had an increased risk of endometrial cancer (relative risk [RR], 2.57, 95% confidence interval [CI], 1.32-4.99).9 Obesity can also be associated with physical inactivity, which has been shown to be an independent risk factor for developing endometrial cancer.10 Women that spend 90 minutes per day doing nonoccupational physical activities have been shown to have a 50% lower risk of endometrial cancer compared with women who spend less than 30 minutes per day. Obesity and inactivity, reported to be increased among some Blacks compared with Whites, may affect the risk of endometrial cancer among some minority women.9 Black women are more than twice as likely to develop Type II diabetes as Caucasians and this increased risk remains even after controlling for BMI and waist-to-hip ratio, suggesting that factors other than obesity alone might be contributing to their increased risk of diabetes.11 Diabetes in turn is associated with insulin resistance, lower sex hormone binding globulin, and a hyperestrogenic milieu that can increase the risk of developing endometrial cancer.12 Although endometrial cancers that develop among diabetic patients do not appear to be pathologically or clinically different from endometrial cancers that develop in nondiabetic patients,13, 14 mortality is increased among endometrial cancer patients with diabetes compared with those without.15
Previous reports have suggested that inequalities in treatment may be an important etiologic factor associated with poor outcome observed in Blacks with endometrial cancer.16 In an analysis of data from approximately 55,000 patients with endometrial cancer contained in the National Cancer Data Base, investigators found that 9% of Black patients did not receive any cancer-directed treatment, compared with only 4% of the White women. Among the patients that received treatment, Black women tended to present with more advanced disease than White patients,17 often requiring lymph node dissection.18 However, the rates of hysterectomy were similar between Blacks and Whites when the data were stratified according to stage. Other investigators using SEER data have found that rates of hysterectomy are lower among Blacks compared with Whites when controlling for stage of disease at diagnosis.6, 17, 19 The reasons why Black patients might not undergo surgery as often are difficult to discern retrospectively using population-based data. In 1 SEER analysis, investigators found that the most common reason for not having a hysterectomy was “contraindicated/not recommended” but further analysis was not performed because of limitations in the uniformity of recording these data across the institutions.6 Although Blacks can present with more advanced disease and can also have a higher likelihood of comorbidities that might influence whether to perform surgery, it is also possible that discriminatory practices by some health care providers or systems may also play a role. In contrast, a Pattern of Care analysis of the SEER database evaluated 711 women with newly diagnosed endometrial cancer and did not identify any differences in primary or adjuvant therapy between Blacks and Whites with endometrial cancer.20 Primary surgery was similar between the 156 Blacks and 419 Whites who were evaluated.20 Adjuvant postoperative radiotherapy has been shown to be similar among Blacks vs Whites, particularly among patients with local disease.6, 19 Similarly, administration of chemotherapy, which is usually reserved for patients with distant metastasis, has not been observed more often in Blacks compared with Whites.6, 17
Data suggest that Black patients may respond differently to surgery and chemotherapy. In an analysis of SEER data, Randall and Armstrong19 revealed that the association between surgery and survival was weaker among Black women (hazard ratio [HR], 0.44) than in White women (HR, 0.26). However, this analysis was not able to control for comorbidities that may have been increased among the Black women. Furthermore, racial differences in treatment by a subspecialty gynecologic oncologist can potentially impact outcome among Black patients with endometrial cancer, because patients managed by another specialist may be less likely to be surgically staged and more likely to have received radiation therapy.21, 22 Recently, a meta-analysis performed by the Gynecologic Oncology Group (GOG) reported a lower response rate for patients with advanced stage and recurrent endometrial cancer who received chemotherapy on 1 of 4 randomized controlled trials. In this analysis, Black women had an overall response rate of 34.9% compared with 43.2% for Whites.23 Although there was no difference in the proportion of Blacks and Whites completing all cycles for the regimen received, there was no information regarding dose reductions/delays that might have biased this observation. Further investigation of differences in response to either surgery or chemotherapy treatment is warranted.
Black patients with newly diagnosed endometrial cancer often present with advanced stage, poorly differentiated, nonendometrioid tumors, suggesting that tumors that develop in Blacks are more aggressive than in Whites.23 Population-based investigations have shown that Blacks have a higher incidence of tumors with nonendometrioid histology rather than a decreased proportion of indolent tumor types.24 This may ultimately translate into worse outcome for Black patients. Sherman and Devesa24 showed that 53% of the total mortality among Blacks was associated with nonendometrioid tumors compared with only 36% of Whites.
In an analysis of data from the GOG, our group recently performed an analysis of advanced stage and recurrent endometrial cancer in an effort to determine whether Blacks have worse survival than Whites when receiving similar treatment for endometrial cancer while participating in a randomized cooperative group clinical trial.24 In this analysis, multivariate regression revealed a 26% greater chance of dying among Blacks compared with Whites even when controlling for comorbidities, stage, histology, tumor grade, performance status, and BMI.25 These findings do not negate the importance of these variables in contributing to the racial disparity in outcome among patients with endometrial cancer. However, the data suggest that other factors may play a role in the disparity in outcome observed in patients with endometrial cancer.
Molecular analysis of endometrial cancers from Blacks and Whites has been performed in an effort to evaluate potential genetic and epigenetic etiologies for differences in observed tumor behavior. For example, mutations in the TP53 tumor suppressor gene, which is associated with poor outcome, have been reported to be more than twice as frequent in endometrial cancers from Blacks compared with Whites (55% vs 25%).26 Additionally, racial disparity in overexpression of the Her-2 oncogene, which is also associated with shortened survival, has been observed more often in Blacks compared with Whites (70% vs 24%).27 In contrast, alterations of the PTEN tumor suppressor gene that is paradoxically associated with favorable outcome is more common in Whites with endometrial cancer than Blacks (22% vs 5%).28 In addition to mutational events, methylation of a gene's promoter region may be an epigenetic mechanism by which changes in gene expression can contribute to the development and progression of endometrial cancer. Investigations of potential epigenetic influences on racial disparity have evaluated methylation of ribosomal DNA and found that endometrial cancers from Whites demonstrate significantly more ribosomal DNA methylation than tumors from Blacks.29 Although each of these molecular analyses suggest a potential biological etiology for racial differences in outcome, the studies have been limited in terms of being able to show associations between molecular alterations and outcome while controlling for other prognostic factors. Nonetheless, they imply that the cancers from Blacks more often develop with a molecular background disposed to more aggressive disease, whereas cancers from whites more often develop from a differing set of defects that tend to result in cancers that are less aggressive.
In 2006 the American Cancer Society estimated that 9710 cases of cervical cancer were newly diagnosed in the US and approximately 3700 women died of their disease. Almost 20% of newly diagnosed cases and cancer related mortality occur in Black women annually.1 Implementation of cytologic screening and standardized treatment algorithms of precancerous cervical pathology have lead to improvements in the rates of cervix cancer among Black women over the past 30 years. However, there are still barriers that may adversely affect optimal screening strategies, particularly among the underserved. In a study by Datta et al.,30 data regarding cervical carcinoma screening was obtained from 40,009 Black participants in the Black Women's Health Study in an effort to identify factors associated with poor compliance with obtaining a regular Pap smear. These women were recruited largely from magazine advertisements and therefore may have represented a more educated and compliant group of women, with almost 92% of the survey responders reporting that they had received a Pap smear in the previous 2 years. In this analysis, lower educational attainment, older age, obesity, smoking, and neighborhood poverty were found to be independently related to a decreased risk of recent screening among Black women.30 In addition, other investigators found in a community-based cross-sectional survey found that only 62% of Black women living in public housing had received recent cytological screening.31 However, 29% of the women claimed that no healthcare provider had ever told them that they needed a screening test for cervical cancer when they had presented for their health exams.31 The findings suggest that optimization of screening among Black and White women should focus on proper education of Black women with risk factors for poor compliance.
Although suboptimal cervix cancer screening can be identified in a significant proportion of Black women, data from the 1987 National Health Interview Survey (NHIS) suggested that Blacks are screened at similar or higher rates than Whites.32 In this study, the proportion of women under the age of 70 having never heard of a Pap smear was higher among Blacks compared with Whites (5.1% vs 2.6%); overall, Black women were significantly more compliant with obtaining Pap smears compared with Whites. A more recent NHIS report33 on data from 2000 indicates that although screening has continued to improve overall, Blacks still appear to have slightly better rates of obtaining Pap smears than Whites. Overall improvements in screening have resulted in a gradual decline in the incidence of invasive squamous cell carcinoma over the past 30 years. However, rates of adenocarcinoma in-situ and squamous cell in-situ lesions still remain higher in Black women compared with White women.34
Population-based investigations have indicated that obesity can adversely affect optimal cervix cancer screening.35 Because there is a higher incidence of obesity in Black women compared with Whites, there has been speculation whether racial disparities in obesity might result in different rates of effective cervix cancer screening, particularly among minority women with a large body habitus. In an analysis of questionnaires from respondents to the 2000 NHIS, investigators evaluated cervical cancer screening taking into consideration BMI 9. In that study of 12,170 women, 3% were underweight, 50% were normal weight, 26% were overweight (BMI ≥ 25 kg/m2), and 21% were obese (BMI ≥ 30 kg/m2). After adjusting for sociodemographic factors, healthcare access, and illness burden, severely obese White women (BMI ≥ 40 kg/m2) were significantly less likely to undergo Pap testing (RR, 0.92) compared with normal weight women.29 However, Black women had similar rates of cervix cancer screening irrespective of body habitus. White women with severe obesity reported that they were more likely to delay screening because of discomfort or embarrassment than normal weight White women.29 In contrast, Black women reported not having recommended screening because of poor physician prompting.36 These findings suggest that obesity does not appear to be an obstacle for optimal cervix cancer screening.
Although there has been an increase in survival for cervical cancer patients in the US over the past 3 decades, 5-year survival for Blacks with cervix cancer remains lower than for Whites. Racial-based inequalities in treatment of disease have been described among cervix cancer patients, with Black patients less often receiving surgery compared with Whites.37, 38 These differences in the frequency of surgery may be related to a higher incidence of comorbidities among Black patients, prompting alternative treatment with primary radiation therapy by providers. The association of race with poor survival in patients with cervix cancer remains controversial. Analysis of SEER data has suggested that Black women with cervix cancer are at a 26% to 30% increased risk of death compared with White women with disease.38, 39 In contrast, studies using multivariate regression models have reported similarities in survival between Blacks and Whites with cervix cancer when controlling for prognostic factors such as stage, grade, histology, and treatment factors.37, 40, 41 Other investigators have suggested that the worse outcome observed in Black patients may be related to racial disparities in access to care or inequalities in the comprehensive level of care. In a study by Farley et al.,42 investigators evaluated cervix cancer patients managed in the US military healthcare system, a medical environment in which patients have no impediments to healthcare access and patients are treated similarly irrespective of their racial or socioeconomic status. This analysis showed that there was no statistically significant difference in 5-year survival between Whites and Blacks, which were 75% and 76%, respectively. Therefore, in an equal access and treatment environment, racial status was not an independent predictor of survival for patients with cervical carcinoma.42
Human papillomavirus (HPV) can be found in 98% of invasive cervical cancers and it is the most common sexually transmitted disease, with reported prevalence rates of 19% to 46%. For any given HPV type, there are variants that are associated with differences in <2% of the DNA sequence for the L1 gene. HPV variants appear to segregate to specific geographical regions, possibly secondary to adaptation of the virus to a specific population over time.43 Because of these geographic differences in the distribution of HPV variants, investigators have evaluated whether HPV variants cluster according to racial status, reflective of the geographical region of origin once shared by the variant. HPV18 associated with Africa was found predominantly (64%) in HPV18-infected Black women, whereas European variants were more common (54%) in HPV18-infected White women. In contrast, HPV18 African variants were found in only 9% of HPV18-infected White women, and European variants were detected in only 24% of HPV18-infected Black women. The persistence of HPV infection also appears to be dependent on the HPV variant and the racial status of the individual. The likelihood of remaining HPV18-positive was statistically significantly higher in White women infected with European variants than in White women infected with African variants (P = .04). The reverse was observed in African American women, with the likelihood of women infected with the African variant of HPV more likely to remain HPV-positive (P = .03). These data suggest that variants of HPV16 persist longer in a host whose race indicates an ancestral geographic distribution that was once shared with that of the variant. Race-associated variant distribution and persistence may either reflect more frequent sexual patterns between individuals of the same race or a biological advantage of certain racial groups to having specific variants.43
Race-associated differences in persistence of HPV may be a result of decreased cellular immunity through a specific immune evasion mechanism within the host. Cell-mediated immunity, important in controlling HPV infection and their associated neoplasms, is regulated primarily by cytokines that are secreted by T helper (Th) cells and macrophages. Th1 cells produce interleukin 2 and interferon (IFN)-gamma, which are immunostimulatory and associated with clearance of the HPV virus.44 Polymorphisms of a number of cytokine genes have been implicated in inducing susceptibility or resistance to cancer caused by infectious agents because of their role in determining host immune response.45 Specifically, polymorphisms of IL-10 and IFN-gamma genes are believed to influence the expression and/or secretion levels of their respective cytokines. A study of South African women with histologically proven cancer of the cervix and hospital-based controls found striking differences in the allele distribution of IFN-gamma between the 2 ethnic groups. A significant increase in the allele distribution of the IFN-gamma African American genotype was found in the African group compared with the mixed population group.46 Although these findings demonstrated a correlation between ethnicity and IFN-gamma polymorphism across different population groups, the differences in ethnicity and gene polymorphisms did not appear to influence the development of invasive cervical cancer. The association between other cytokines and cervical cancer needs to be further explored, particularly in the context of explaining racial disparities in the development of HPV-mediated cervical pathology.
Over 20,000 new cases of ovarian cancer are diagnosed annually in the US.1 Estimates from the SEER program indicate that approximately 1610 of the new cancers occurred in Black women in 2005.8 Black women have a lower incidence of ovarian cancer than Whites, with age-adjusted rates ranging from 13.1 per 100,000 for Whites to 9.0 per 100,000 for Blacks. The rates of mucinous, endometrioid, and clear cell ovarian cancer are lower in Blacks, leading to racial disparities in the incidence of ovarian cancer that are dependent on the histologic subtype of tumor being evaluated.47 Although there has been a gradual decline in the incidence in ovarian cancer over the past 30 years, incidence rates have fallen slightly less among Caucasians compared with Blacks (ie, 9.9% vs 12.8%).48 Several reproductive factors have been evaluated in an effort to explain the racial disparity in ovarian cancer incidence between Blacks and Whites.49, 50 The data indicate that Black women are more likely to have breast-fed for 6 months or longer49 and to have experienced multiple pregnancies,49, 50 events that decrease the likelihood of ovulation, which has been associated with ovarian cancer risk. In addition, Blacks are more likely to have undergone a hysterectomy and less likely to have a family history of ovarian cancer when compared with White women.50 The presence of other unacknowledged biological and environmental factors related to ovarian cancer is felt to further contribute to the observed racial disparity in ovarian cancer incidence.49
Although improvements in contemporary management of ovarian cancer (to include optimal surgical cytoreduction and more effective adjuvant chemotherapy) have accompanied a decline in cancer-related mortality over the past 30 years, survival does not appear to have improved for all racial groups.51 Whereas significant improvements in 2-year survival and in 5-year survival have been noted among White women over the past 3 decades, there have not been similar improvements in survival among Blacks over this 30-year period.1, 52 Stratified analysis by stage has confirmed that outcome is worse for Blacks compared with Whites for every stage of disease. Multivariate regression has also shown a racial disparity in outcome for Blacks even when controlling for age, stage, and histology.53, 54
Cytoreductive surgery is acknowledged as an important component of comprehensive therapy for advanced stage ovarian cancer and racial differences in its utility may contribute to disparities in cancer-related outcome. Using the National Cancer database, Parham et al.55 reported that Blacks were less often treated with combined surgery and chemotherapy and more often treated with chemotherapy alone. Although race did not affect the type of surgery performed, the authors reported that surgery was performed less often among Black patients with ovarian cancer.54 Similar findings have been noted in analysis of data from the SEER program in which the proportion of Black women undergoing surgery as part of primary treatment was lower than for any other racial group.52, 53 In 1 report the odds that a Black patient would not undergo surgery were 40% higher than the odds that a White patient would not have an operative procedure52; however, when the data were stratified the distribution of surgery by stage was similar between Blacks and Whites, suggesting that disparity in rates of surgery between these 2 groups may be related to differences in the extent of disease at the time of presentation. Black patients more often present with stage IV disease,51, 54, 55 which may influence a surgeon's enthusiasm to pursue primary surgical cytoreduction as opposed to neoadjuvant therapy. In addition, many of the population-based studies that have evaluated racial differences in surgery for ovarian cancer have not controlled for comorbidities,51, 52, 55 which are increased in Blacks and can influence decisions regarding inclusion of aggressive surgical cytoreduction in the treatment plan.
Many of the studies evaluating survival among Blacks with ovarian cancer have utilized the SEER database, which provides limited information regarding the details of surgery or chemotherapy regimens that patients received. In an effort to further evaluate trends in surgery and chemotherapy received by patients with ovarian cancer, investigators reabstracted medical records from a sample of patient cases from the SEER program.56 Treatment data were verified with the treating physician in order to determine whether the patients received guideline therapy as outlined by the NIH consensus conference on ovarian cancer.57 Although univariate analysis revealed that fewer minority patients received guideline therapy compared with non-Hispanic Whites, further analysis found that there was no statistically significant differences in the use of guideline therapy by Blacks and Whites when the model controlled for age, marital status, availability of insurance, comorbidity index (Charlson score), and the presence of a residency program where the patient received treatment.56 In another study, investigators used the California Cancer Registry to perform a population-based study evaluating patterns of chemotherapy utilization by ovarian cancer patients. In that analysis the probability of receiving treatment was not associated with racial status, even after controlling for age, stage, grade, and whether the patient was treated by a board-certified surgeon who was subspecialty-trained in gynecologic oncology.58 Although these 2 studies suggest that similar proportions of Blacks and Whites receive chemotherapy, future investigations are necessary to confirm whether dose intensity and the number of cycles completed is similar between Blacks and Whites receiving treatment.
In an effort to determine whether racial disparities in survival exist in a healthcare system where patients have equal access and are treated similarly irrespective of race, investigators evaluated over 1500 women with ovarian cancer participating in the Kaiser Permanente Medical Plan of northern California and over 5700 nonmembers with ovarian cancer.53 In that analysis, ovarian cancer death rates, adjusted for age, stage, and histology, were higher for Blacks compared with Whites, regardless of Kaiser status,53 suggesting that additional factors are important contributors to worse outcome observed among Black patients with ovarian cancer. Our group similarly evaluated prognostic factors in a retrospective analysis of 6 clinical trials conducted by the GOG that utilized platinum and paclitaxel in the adjuvant treatment of advanced stage ovarian cancer. When controlling for other prognostic factors, race was not associated with progression-free survival or overall survival in a clinical trial setting in which patients received similar treatment on protocol.59
A biologic etiology for the racial disparity in ovarian cancer outcome has not been elucidated. However, there do appear to be racial differences in the types of molecular alterations that are associated with the approximately 5% of ovarian cancers that are associated with germline BRCA1 and BRCA2 mutation. In 1 study the entire coding region of 1 and BRCA2 was sequenced in Blacks identified from a multiethnic cohort in an evaluation of the frequency and nature of BRCA1 variants among these underserved patients. Compared with non-Hispanic, non-Jewish whites, Blacks had a lower rate of deleterious BRCA1 and BRCA2 mutations (27.9% vs 46.2%) but a higher rate of sequence variations (44% vs 11%).60 Because many of these minority women with a family history of disease had no evidence of protein-truncation or obvious disease-associated missense mutations, these data suggest that mutations in other genes might contribute to the increased risk of cancer in this cohort of minority families. Other authors have identified mutational changes (ie, 1993delAA and 8643delAT) that appear to be unique for women of African ancestry.61, 62 With this in mind, a more effective method for genetic testing of Blacks might include sequencing of the entire coding and flanking noncoding regions of the BRCA genes, as opposed to mutational screening of a panel of founder mutations that may not be as effective.
There are significant racial disparities in outcome among women with gynecologic cancer. Most of the data would suggest that Black women with gynecologic cancers more often present with metastatic tumors that behave aggressively when compared with White women with disease. Currently, there is limited published evidence describing problems with access to care among minorities as it pertains to medical evaluation for gynecologic cancer. Barriers prohibiting timely diagnostic evaluation of underserved populations can potentially result in some patients presenting with more advanced forms of disease. These obstacles may not only be a reflection of the healthcare system but also a reluctance of Black women who seek care. Investigators have reported that Blacks are more likely not to trust their physicians than Whites even after controlling for socioeconomic factors. Many Black women may have a belief that minority women are treated unfairly and a lower education background in some Black women may further adversely affect physician-patient communications particularly if they are cross-cultural. A fear of treatment-related costs may also prevent underserved patients from accessing the healthcare system for symptoms that might suggest a gynecologic problem. Finally, specific healthcare systems may present obstacles that delay uninsured patients from gaining timely management.63 Further investigation of healthcare access for Black women with gynecologic problems is necessary to identify potential barriers that prevent patients from being diagnosed with less advanced cancers. Alternatively, Black women may present with more advanced tumors that reflect tumors that have biologic alterations associated with more aggressive behavior when compared with gynecologic cancers from White women. Although there have been many that have rejected the concept that there are no biologic differences between racial groups that account for disparities in medical problems, others have suggested that environmental exposures, along with underlying genetic risk, may contribute to the behavior displayed by a specific tumor. Epigenetic modulation of gene expression within a given tumor may be determined by the culturally and socially defining characteristics of a particular racial group, leading to a unique tumor phenotype.64 Additional research is necessary to determine whether certain cancers are biologically different between Black women and White women with tumors that are matched for known poor prognostic features. These types of findings might prompt individualized treatment based on the molecular profile of the patient's tumor in the future.
Previous reports have suggested that Black women with gynecologic cancer receive unequal treatment compared with White women and that this may explain the worse outcome among these underserved patients in population-based studies. Future population-based analysis should take into account both SES as well as comorbidities as well other important clinicopathologic prognostic factors in accurately evaluating potential differences in treatment between Blacks and Whites with gynecologic cancer. Conclusions regarding inequalities in treatment of gynecologic cancer between Black and White women should confirm that minority women were not treated differently because of coexistent medical problems that prohibited surgery, low SES, or other pathologic factors associated with their tumor that influenced outcome.
According to the US Census, the Black population in the US is expected to nearly double its present size to 61 million by the year 2050.65 Improved public awareness regarding health disparities research is needed to address healthcare issues in this increasing population of patients. Additional research should seek to clarify the underlying causes of cancer disparities and more importantly develop strategies to remove the barriers that adversely affect optimal detection and treatment of underserved minority populations.
- 59Prognostic factors for stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2004; 92: 412., , , et al.
- 65Available at: http//www.census.gov/prod/3/98pubs/p23-194.pdf