Introduction
Breast cancer is the most common malignancy affecting women of every race and ethnic group worldwide. In the United States, 1 in 8 women will develop breast cancer in her lifetime, although the incidence and mortality rate varies among different races.[1]
Due to significant advances in early detection and available therapies, the overall mortality rate of breast cancer is declining in the United States, though not all races or ethnicities have benefited equally.[2] The incidence of late-stage diagnosis and overall mortality remains higher among certain minority groups, especially Black women. Similar inequities exist at every phase of breast cancer care, from initial screening to timely follow-up and appropriate therapy completion. These substantial disparities are thought to be multifactorial with cultural, environmental, biological, and systems-based issues all contributing.
Studies have identified strategies to reduce racial disparity in breast cancer outcomes and improve all women's clinical care. Still, the broader implementation of these existing strategies needs to take place. Furthermore, interprofessional teams must work together to innovate new policies to reduce the racial gap seen in disease-free survival rates and institute the necessary changes to achieve those goals and provide the highest quality of care to all women.[3][4]
Issues of Concern
Racial Disparities in Outcomes
Breast cancer is the most common malignancy seen in women, excluding non-melanoma skin cancers. However, breast cancer does not affect all racial groups equally. Non-Hispanic White women are more likely to be diagnosed with breast cancer than any racial group, followed by Black, Asian/Pacific Islander, Hispanic, and American Indian/Alaska Native women with a lower incidence rate. In recent years, studies have shown an overall increase in the incidence of breast cancer in the United States, with the largest increases noted among Black and Asian/Pacific Islander women. In contrast, the incidence has remained stable among non-Hispanic White, Hispanic, and American Indian/Alaska Native women.
Yet, there is a troubling reality about the mortality rates for women with breast cancer. While the 5-year survival rate has increased for all women over the last 40 years, a substantial racial gap persists. The incidence of breast cancer is now quite similar between non-Hispanic White and Black women in the United States, yet Black women are 42% more likely to die from the disease. Black women are more likely to die of breast cancer than any other racial group at every age, even among patients with similar staging and tumor subtypes. Not only do Black women have higher mortality rates, but they are more often first diagnosed at regional or distant stages when compared with non-Hispanic White women (45% versus 35%).[3][5]
Similarly, Hispanic women have a lower incidence of breast cancer than non-Hispanic White women. However, their breast cancers are often diagnosed at a later stage leading to poorer outcomes.[4] Such disparities exist at every phase along the breast cancer care continuum, from early screening and diagnosis to treatment initiation and completion.[3] Though the magnitude each separate force plays is often debated, the disturbing racial disparities seen in cancer outcomes are clearly driven by multiple factors, including but not limited to differences in tumor biology, socioeconomic status, decreased access to healthcare, increased prevalence of risk factors, and co-morbid conditions, medical mistrust, and suboptimal patient-physician interactions.[5]
Risk Factors
All people are at risk of developing breast cancer, though several factors have been shown to alter an individual’s risk. The two strongest demographic features are gender and age. Although men are diagnosed with breast cancer at a rate of 1 in 1000, being female is the greatest single risk factor for breast cancer, with 1 in 8 women diagnosed throughout her lifetime. Age is another significant risk factor for developing breast cancer. With advancing age, the risk of breast cancer rises significantly until the age of approximately 75, at which point the risk begins to drop off again. The median age at the time of diagnosis is 61, though both Black and Hispanic females have a higher incidence of being diagnosed at younger ages. This may play a role in their increased rate of advanced disease at the time of diagnosis, although many other factors contribute to the disparity as well.[4][6]
Reproductive factors such as early age of menarche, late onset of menopause, nulligravidity, advanced age at first pregnancy, hormone therapy, oral contraceptive use, duration of lactation, and high breast density have all been tied to increased breast cancer risk and vary among racial groups. Modifiable risk factors such as obesity, diet, exercise, and alcohol consumption have also been linked to breast cancer. Studies indicate that physical activity reduces breast cancer risk by lowering levels of insulin and insulin-like growth factor I and assisting with weight maintenance to avoid a high body mass index (BMI). A BMI of greater than 35 kg/m^2 has been shown to double the risk of breast cancer. Many epidemiological studies have found a linear increase in breast cancer risk with increasing alcohol consumption as well. Other lifestyle factors such as smoking, vitamin D levels, duration of sleep, air pollution, and night work are associated with increased rates of breast cancer. Many of these risk factors are inextricably related to social, cultural, environmental, and genetic predispositions, which contribute to the racial disparities seen in breast cancer outcomes, and thus, must be addressed on a systems-based level.[7][8][9]
Breast cancer outcomes, as well as its risk factors, vary not only between racial groups but also within the socioeconomic status. Poverty is a critical driver of health disparity and is associated with poorer breast cancer outcomes among all women, regardless of race. However, because a larger proportion of minority women live in poverty, the barriers to health associated with low socioeconomic status fall more heavily on them. Low-income women have less access to early breast cancer screening and, therefore, a greater probability of late-stage diagnosis. They more often receive inadequate and disparate breast cancer treatment, which leads to higher mortality rates. Many poor communities lack the vital infrastructure providing access to primary care clinics or specialized physicians. Women living in poverty are less likely to have adequate health insurance. Studies have shown that Black women are two times as likely to be uninsured or to depend on public insurance as non-Hispanic White women, a finding in which socioeconomic status plays a large role. A recent survey of breast cancer survivors found that financial constraints prevent many minority women from accessing appropriate, timely follow-up care. Over half of the Black women who participated in the survey identified anxiety over out-of-pocket expenses as a major barrier to receiving healthcare.[5]
Lower socioeconomic status has been linked to less education, poorer nutrition, and physical inactivity, much of which stems from social injustices such as limited school funding, decreased access to healthy foods, and lack of safe recreational spaces. All these social inequities lead to an increased prevalence of co-morbidities such as obesity, diabetes, and cardiovascular disease, which, in turn, increase the risk for breast cancer. Minority women are disproportionately affected by these socioeconomic factors contributing to breast cancer disparity. However, even when socioeconomic status is considered, studies suggest that racial disparities in breast cancer outcomes persist, indicating that other contributing factors exist.[4]
A family history of breast cancer is one of the most widely known risk factors for developing the disease. Women with a family history of breast cancer are nearly 11 times more likely to develop the disease. That risk increases even further when inheritable gene mutations exist. Roughly 10% of breast cancers are hereditary. Of those, nearly half are due to BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) gene mutations.[1]
The autosomal dominant BRCA1 and BRCA2 gene mutations are located on chromosomes 17 and 13, respectively. They produce tumor suppressor proteins that help repair damaged DNA. When these genes do not function properly, DNA damage is not adequately repaired, and cells are more likely to undergo genetic alterations leading to cancer development. The prevalence of these mutations varies by ethnicity. The highest rates of BRCA 1 mutations occur among Ashkenazi Jewish women (8.3%), followed by Hispanic women (3.5%), non-Hispanic White women (2.2%), Black women (1.3%), and Asian women (0.5%). Over half of the women who inherit a BRCA mutation will develop breast cancer by the age of 70. Moreover, women with BRCA mutations are more likely to develop secondary cancers such as ovarian cancer or contralateral breast cancer. They are also more likely to develop “triple-negative” cancer, which has a poorer prognosis than other breast cancers. Therefore, it is recommended that women with early-onset breast cancer or women with a family history consistent with a possible BRCA mutation have genetic testing when breast cancer is diagnosed. As gene sequencing continues to advance, other mutations increasing the risk for breast cancer have been identified as well. Some of the more common gene mutations include PTEN, TP53, MLH1, MLH2, STK11, ATM, CDH1, CHEK2, and PALB2, which should be included in genetic testing in appropriate cases.[4]
The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the most commonly used classifications of tumor biology in invasive breast cancer. The degree of tumor positivity to these receptors determines therapeutic approaches and can help predict clinical outcomes. The incidence of different hormone receptor-positive breast cancer varies by ethnic group. Women of color tend to have higher rates of ER/PR negative breast cancers, which can limit treatment options and lead to worse clinical outcomes. Black, Native American, Filipino, Chinese, Korean, Vietnamese, Indian/Pakistani, Mexican, South/Central American, and Puerto Rican women living in the United States were shown to be 1.4 to 3.1 times more likely to have ER/PR negative breast cancer when compared to non-Hispanic White women.[1][10]
In addition, Black and Hispanic women are more likely to have tumors greater than 2cm in diameter at the time of diagnosis with poor differentiation and significant nuclear atypia. Furthermore, ER/PR/HER2 negative (“triple-negative”) tumors are more common among Black and Hispanic women. “Triple-negative” tumors are notoriously less responsive to standard treatments and thus portend a worse prognosis than other tumor subtypes.[4][6] This over-representation of “triple-negative” tumors likely contributes to the increased breast cancer mortality seen among minority women. Importantly, survival disparities still persist within the hormone-receptor-positive tumors that carry a better prognosis, confirming that the racial gap seen in late-stage diagnosis and mortality rate cannot be accounted for solely by differing tumor mechanisms.[11][12]
Clinical Significance
Differential access to healthcare is an important contributor to breast cancer disparities in the United States. Access to care varies from neighborhood to neighborhood, in part due to historical patterns of segregation and structural racism. It also varies from city to city because of systems-based factors such as state policy decisions, differential Medicaid coverage and re-enrollment requirements, and funding of social programs.[13] Though some neighborhoods or cities may be more prone to barriers limiting healthcare access, racial disparities exist at every step along the breast cancer care continuum from early screening and timely diagnosis to initiation and completion of high-quality therapies throughout the United States.[11]
Extensive research has established that regular breast cancer screening can detect tumors at an earlier stage and result in improved survival and better prognosis. Yet minority women are more likely to have longer intervals between screening mammograms, which contributes to the higher rate of late-stage diagnosis within Black and Hispanic populations.[3] Furthermore, minority women were less likely to be screened at breast imaging centers of excellence or facilities with digital mammography and dedicated breast radiologists. Studies have found that, consequently, the probability of missed detection is higher among both minority women and women with lower socioeconomic status when compared to non-Hispanic White women or those from socioeconomically advantaged backgrounds. Though routine screening to promote early-stage breast cancer diagnosis is strongly advocated by the most prominent national clinical guidelines, disagreement has arisen over the age at which a patient should initiate screening.[13]
Screening guidelines do not uniformly take into account the differences in age at the time of diagnosis seen between racial groups. One study found that approximately 23% of non-Hispanic White women and 37.5% of Black women with breast cancer presented under the age of 50 years.[8] Similar trends of younger age at the time of diagnosis are seen among Hispanic women as well. Yet, the United States Preventive Services Task Force (USPSTF) recommends that women of average risk for breast cancer undergo screening every other year starting at age 50. These guidelines may increase the racial disparity given the higher prevalence of minority women who develop breast cancer prior to the age at which routine screening is initiated.[13]
Beginning treatment in a timely fashion after an abnormal screening test is critical to obtaining optimal outcomes. Delays in follow-up after an abnormal mammogram can lead to larger tumors with more lymph node involvement, and subsequently, poorer outcomes. Timeliness and adequacy of follow-up vary independently by socioeconomic status, health system characteristics, and race. On average, Black women have longer intervals from an abnormal mammogram to diagnosis than non-Hispanic White women, even among those with similar insurance status. Specifically, 20% of Black women had intervals to diagnosis greater than 60 days compared to only 12% of non-Hispanic White women. Similar delays in initiation of treatment after diagnosis are seen among minority women. Multiple studies show that Black and Hispanic patients more frequently have significant delays in initiating chemotherapy.[11]
Only 69% of Black women start treatment within 30 days of diagnosis compared to 82% of non-Hispanic White women, according to one analysis.[3] Another study demonstrated that >25% of Black women experienced 3 or more months of clinical delay in initiating treatment.[8] In addition to the social inequities leading to these disparities, medical mistrust due to a history of experimentation and abuse endured by Black communities may also play a role in the delay of care. For example, Black women are less likely to seek surgery compared to women of other racial groups, therefore limiting their treatment options and contributing to increased mortality. Mistrust of the medical community has been shown to influence how Black women manage their health and could amplify the breast cancer disparities seen between Black women and other racial groups, and thus, must be addressed.[4]
Not only do many minority women face longer intervals before initiating treatment, but they are at risk of receiving inferior care in a multitude of ways. Differences in the quality of care often stem from the institutions where minority patients seek care. Minority women are more likely to receive treatment at hospitals without a National Cancer Institute (NCI) comprehensive cancer center designation, which equates to slower adoption of innovative therapies, lower rates of sentinel lymph node biopsies, and less access to morbidity-sparing surgical procedures and breast reconstruction. The racial discrepancies seen in the receipt and timeliness of adjuvant radiation were largely influenced by the type of facility at which a patient received surgery and/or the distance to a radiation care center. Black women are more likely to receive reduced-intensity adjuvant regimens and under-dosing of chemotherapy due to inappropriate “capping” of doses for overweight patients. They are less likely to receive newer targeted therapies and more likely to undergo non-standard chemotherapy in combination with the HER2-targeted agents when compared to non-Hispanic White women within the Medicare program. Even at comprehensive cancer centers, Black women are less likely to complete a full course of adjuvant trastuzumab, suggesting that better insurance or access to renowned facilities is not enough to eliminate the racial disparities in breast cancer.[11]
The significant decline in breast cancer mortality is, in part, due to the advent of endocrine therapy targeted at hormone-dependent tumors. Compared to Non-Hispanic White women, though, Black women with ER/PR positive breast cancer were less likely to have been recommended for or to have been started on endocrine therapy.[12] The disparities extend through post-treatment cancer care as well, with fewer minority women accessing dietary, rehabilitation, reconstructive, or mental health services. The continued growth of breast cancer disparities among minority women suggests that the current approaches to preventing or eliminating racial gaps are not sufficient. Therefore, new strategies are needed to promote prevention, reduce mortality, and improve the breast cancer outcomes of minority women.
Enhancing Healthcare Team Outcomes
The inequitable care often received by minority women is striking. As we have elucidated, breast cancer outcomes are driven in part by a lack of access to care within a given health system. This highlights the need for innovative methods of delivering cancer care and eliminating barriers for the most vulnerable patient populations.[11]
Several strategies to combat breast cancer disparities have been proposed. Implementation of these strategies, which focus on increasing healthcare access, is more important than ever with the current national debates over the viability of Medicaid expansion or the potential reversal of the Affordable Care Act. First, it is critically important that minority populations have representation among the political leaders, researchers, and medical professionals in the decision-making processes regarding medical research, national screening guidelines, healthcare delivery, social policies, and public health interventions so that racial disparity in breast cancer can be more fully addressed.[4]
Multiple studies have shown that policy factors such as decreased co-payment, availability of generic alternatives, and low-income subsidies can increase adherence to endocrine therapy among minority women, in turn, potentially improving outcomes. Furthermore, interventions such as patient navigation can help mitigate differences in health literacy, self-advocacy, and access to resources, which can improve the timeliness of diagnosis and initiation of treatment.[11]
Other evidence-based interventions that increase early breast cancer screening and timely follow-up include group education, one-on-one patient education, client reminders, reduction of out of pocket expenses, performance-based provider reimbursement, and quality assurance–reporting protocols. Feedback interventions have the potential to improve cancer care through automated functions that alert providers when gaps in care occur. In addition to social, cultural, economic, and environmental factors, it is becoming apparent that biologic factors also contribute to racial disparity. Accordingly, allocating more funds toward research of the underlying mechanisms of more aggressive tumors within minority populations could help develop effective treatment strategies against these subsets of tumors.[12]
Moreover, an examination of conflicting mammography screening guidelines may lead to new, more inclusive models of generating national breast cancer recommendations and more nuanced guidelines for minority women.[13] More equitable distribution of high-quality mammography screening and improved access to timely surgical care are proven strategies for reducing racial disparity in breast cancer outcomes.[14]
As providers, it is imperative that we advocate for and implement the various strategies proposed in order to make breast cancer care equitable among all women. The ultimate goal should be high-quality, timely care at each step along the pathway from early screening to post-treatment follow-up. Only then can we continue to lower the mortality rate and improve outcomes for all women with breast cancer.
Disparity in Early Detection of Breast Cancer