The Landmark Series—Addressing Disparities in Breast Cancer Screening: New Recommendations for Black Women

Abstract

Randomized, clinical trials have established the efficacy of screening mammography in improving survival from breast cancer for women through detection of early, asymptomatic disease. However, disparities in survival rates between black women and women from other racial and ethnic groups following breast cancer diagnosis persist. Various professional groups have different, somewhat conflicting, guidelines with regards to recommended age for commencing screening as well as recommended frequency of screening exams, but the trials upon which these recommendations are based were not specifically designed to examine benefit among black women. Furthermore, these recommendations do not appear to incorporate the unique epidemiological circumstances of breast cancer among black women, including higher rates of diagnosis before age 40 years and greater likelihood of advanced stage at diagnosis, into their formulation. In this review, we examined the epidemiologic and socioeconomic factors that are associated with breast cancer among black women and assess the implications of these factors for screening in this population. Specifically, we recommend that by no later than age 25 years, all black women should undergo baseline assessment for future risk of breast cancer utilizing a model that incorporates race (e.g., Breast Cancer Risk Assessment Tool [BCRAT], formerly the Gail model) and that this assessment should be conducted by a breast specialist or a healthcare provider (e.g., primary care physician or gynecologist) who is trained to assess breast cancer risk and is aware of the increased risks of early (i.e., premenopausal) and biologically aggressive (e.g., late-stage, triple-negative) breast cancer among black women.

Graphical Abstract

Breast cancer (BC) is the most commonly diagnosed cancer among women in the United States and is estimated to affect more than 281,550 women in 2021 alone.¹ However, incidence and mortality trends vary across different racial groups. Historically, black women—defined as women who trace their ancestry to sub-Saharan Africa—have had lower incident rates of breast cancer than white women, but the incidence of BC among black women has increased with the addition of mammography screening, leading to a convergence in incidence rates among black and white women over time. In contrast, BC death rates among black and white women have been diverging since the 1980s.²

It is well established that breast cancer screening can lead to early detection and improved survival³; yet screening recommendations for women of all races differ between various professional organizations. This heterogeneity in screening recommendations may disproportionately affect black women in the United States due to differential population rates of tumor biology, socioeconomic factors, and disparities in healthcare delivery.

We recognize that race is a social construct, is sometimes used as a highly imperfect proxy for genetic ancestry, and often is associated with poor outcomes among individuals from particular racial groups in part because of the racism experienced by those groups.⁴ Nevertheless, given the fact that black women—for multiple reasons—are more likely to present with breast cancer at a younger age and with more aggressive disease, it is important to examine whether different screening guidelines for black woman would be appropriate and could be a means through which disparities in stage at presentation and outcome after diagnosis can be addressed.

This paper explores the epidemiologic and socioeconomic individual and systemic factors affecting black women with breast cancer and provides recommendations for risk assessment and screening that may serve to address current disparities in breast cancer stage at presentation and outcome following diagnosis.

EPIDEMIOLOGY AND BIOLOGICAL FACTORS

Despite a slightly lower incidence of breast cancer among black women relative to white women (126.7 vs. 130.8 per 100,000), mortality rates are 42% higher among black women.^2,5 While mortality rates were comparable until the 1980s, mortality rates have since diverged significantly. Racial mortality differences exist at all ages and across all stages of presentation; this difference is especially pronounced among black women < 50 years, who have a mortality rate of approximately twice that of whites (11.0 vs. 6.3 deaths per 100,000).^2,6,7 These increased mortality rates among black women compared with other ethnic and racial groups persist when controlled for socioeconomic factors, thereby highlighting that race does not serve as a surrogate for socioeconomic status, and there are more complicated social and biologic factors involved.^8,9

Breast cancer presents at younger ages among black women, at a median age of 58 years compared with 62 years in white women, with a higher incidence of breast cancer among women under 40 (70.6 vs. 59.9 per 100,000).^5,10,11 While young age at presentation is an independent risk factor for higher mortality, breast cancer-specific survival appears to be modulated by molecular subtype with larger differences in mortality rates observed among young women with hormone receptor-positive (HR+) tumors.¹² Despite the fact that black women are twice as likely to be diagnosed with the more aggressive triple-negative breast cancer (TNBC) phenotype compared to white women,² the mortality gap between Black and white women is driven by differential survival following diagnosis with HR+ disease.

However, disparities in outcome after breast cancer are due to many factors, among which tumor biology and screening behavior are only two. Importantly, both individual and systemic biases are important contributors to disparity. Bias—both implicit and explicit—on the part of providers plays a significant role in the doctor-patient relationship and counseling that a patient may receive. The increased rates of medical comorbidities, including diabetes and hypertension, are observed among black women; these along with benign ethnic neutropenia have been associated with decreased rates of chemotherapy receipt and concomitantly worse survival.^13,14 Because screening recommendations often are made by providers in the context of perceived life expectancy, the presence of more comorbidities and suboptimal control of those comorbidities among black women may contribute to their under-referral for screening mammography.^15,16 The magnitude of the role of implicit bias and reduced access to care in explaining these findings is challenging to quantify but must not be overlooked.

Epidemiological factors certainly play a role in disparities in breast cancer, but there is evidence that receptor subtype plays a role in outcomes, with black women more likely to be diagnosed with triple-negative breast cancer, which could in part drive the statistically poorer outcomes.^17–20 These increased rates of TNBC have been linked with germline genetic patterns of West African ancestry identified in black women in the United States.^21–23 The differences in outcomes were noted in an examination of National Comprehensive Network data, identifying ethnically based differences in breast cancer-specific death related to receptor type. Black women were noted to have a poorer survival overall, which persisted after controlling for tumor factors and socioeconomic status. Interestingly, there was no statistical difference in outcomes between black and white women diagnosed with TNBC or HER2+ breast cancer when controlling for similar factors, including stage.²⁴ Sparano et al. performed a retrospective examination of data from a prospective, randomized trial examining systemic therapy for women in the treatment of breast cancer. Black women had a higher incidence of TNBC (31.9% vs. 17.2%, p < 0.001) than white women, but without a significant difference in survival for either TNBC or HER2+ breast cancers when compared equally based on the extent of disease.¹⁸ Multiple other studies have noted similar survival in these two receptor subtypes regardless of race.^25–27 Interestingly, the Carolina Breast Cancer Study utilized immunohistochemical markers to subtype 1149 breast cancers, noting that white patients with TNBC had a slightly higher mortality than black patients with TNBC (hazard ratio [HR] = 2.0, 95% 1.2–3.4 vs. HR = 1.5, 95% 1.0–2.4).²⁷ Thus, the biological differences in the incidence of TNBC in black patients do not present the complete picture of the breast cancer disparities.

The hormone receptor subtype is emerging as playing a major role in outcomes for black women. Additional results from the aforementioned Carolina Breast Cancer Study noted Bblack women had a lower incidence of HR+ breast cancer and a higher breast cancer-specific mortality, but noted that this mortality was only significantly higher in luminal A tumors.⁷ Additional analyses confirm the findings of significantly lower overall and breast cancer-specific survival for AA women with HR+/HER2− breast cancer.^18,26 There are several proposed reasons for these disparate outcomes. In terms of treatment, it is clear that endocrine therapy can improve survival for patients with HR+ breast cancer.^28–30 Several studies point to the lower rate of adherence in black patients.^31,32 Specifically, Friese and colleagues examined endocrine therapy in patients diagnosed with HR+ breast cancer and noted that black women were more likely to start endocrine therapy (odds ratio [OR] 3.63, 95% 1.22–10.78), but less likely to continue treatment (OR 0.72, 95% 0.38–1.38).³³ Further studies on the issue of adherence to endocrine therapy found that black patients had a lower rate of adherence compared with white patients, regardless of age (age ≤62, OR 0.51, 95% 0.39–0.68 and age >62, OR 0.51, 95% 0.40–0.63).³⁴ Although not the sole explanation for the survival disparity in breast cancer-specific survival for HR+ disease, adherence to endocrine therapy certainly plays a role.

Another potential contributor to racial disparities in outcome is differential expression of estrogen receptors (ER). In an examination of ER expression, researchers found an inverse relationship between ER expression and breast cancer-specific survival. This inversed correlation was not seen in black patients.³⁵ Reding et al. examined single nucleotide polymorphisms (SNP), haplotypes, and SNP-hormone therapy (HT) interactions in patients that were part of a large case-control study. They found racial differences in SNP-HT interactions within the estrogen metabolism pathway could exist.³⁶ More recently, the emergence of genomic testing has helped to elucidate biologic differences further. In recent National Cancer Database and Surveillance, Epidemiology, and End Results (SEER) Program examinations, Oncotype DX Recurrence Scores (RS) and Mammaprint results in black women were consistently higher when matched stage for stage. They provided for a lower prognostic value of equivalent risk scores.^37,38 An examination of RS in the TAILORx study, Albain et al. noted that black women had higher recurrence rates and lower survival rates for intermediate risk recurrence scores with a similar lack of benefit from chemotherapy.³⁹ Similar results were achieved from an examination of PAM50 subtyping, noting that young black women have the highest percentage of nonluminal HR+ tumors, which could contribute to lower survival and increased recurrence rates even with equivalent treatment approaches.⁴⁰ These studies point towards possible differential sensitivities to endocrine therapy, questions of adherence, and/or other yet to be determining factors.

Finally, contributing to the mortality gap is the observation that breast cancers are diagnosed at more advanced stages among black women. Indeed, only 50% of breast cancers in black women present with breast-only disease compared with 67% of cancers in white women.¹¹ Similarly, regional disease is present in approximately 33% of black women at the time of diagnosis compared with 25% of whites.¹⁰ These differences had historically been attributed to lower rates of mammography participation, but in fact, black, Asian, Hispanic, and white women have comparable rates of screening mammography, although lower rates continue to be observed among Native American women.⁴¹ Rather, one contributor may be the fact that black women may be more likely to develop breast cancer before ever obtaining a screening mammogram, an ever greater possibility as some organizations (e.g., American College of Physicians and United States Preventive Services Taskforce) advocate delaying annual mammograms until age 50 or older for women at average risk for breast cancer.⁴²

In summary, biological factors including higher rates of TNBC among black women due to higher rates of West African ancestry and possible differences in ER expression, treatment-related factors, including differential and often biased administration of chemotherapy and endocrine therapy contribute to disparate outcomes for black women through a number of mechanisms both known and emerging, and systemic factors related to screening engagement and societal guidelines. Research continues to attempt to better clarify these differences and translate that knowledge into improved screening, diagnosis, and treatment of breast cancer in black women.

RECOMMENDATIONS FOR RISK ASSESSMENT AND SCREENING

Controversy surrounds breast cancer screening guidelines in the United States, recommendations that impact women of all races and ethnicities. While the importance of breast cancer screening and its role in early diagnosis is universally accepted, there are conflicting recommendations from various national and international health organizations regarding the optimal age of screening onset and the optimal frequency of screening mammography for those at average lifetime risk of breast cancer (Table 1). There also is a lack of consensus on when and how to identify women at elevated risk of breast cancer and how to provide supplemental screening to this population.

TABLE 1.

Summary of current breast cancer screening guidelines for women of average risk

	Age 40–44	Age 45–49	Age 50–54	Age 55–74	Age 75+
American Society of Breast Surgeons43	Annual	Annual	Annual	Annual	Annual until life expectancy <10 yrs
U.S. Preventative Services Task Force44	Optional - Biennial	Optional - Biennial	Biennial	Biennial	Insufficient Evidence to Assess
American Cancer Society45	Optional - Annual	Annual	Annual	Annual or Biennial	Annual until life expectancy <10 yrs
American College of Physicians (ACP)46	Optional - Biennial	Optional - Biennial	Biennial	Biennial	Insufficient Evidence to Assess
American College of Obstetricians and Gynecologists (ACOG)47	Annual or Biennial	Annual or Biennial	Annual or Biennial	Annual or Biennial	Shared-Decision based on health status and longevity
American College of Radiology48	Annual	Annual	Annual	Annual	Shared-Decision based on health status

Experts from The American Society of Breast Surgeons (ASBrS) previously and extensively reviewed data from randomized, control trials (RCTs), observational studies, and peer-reviewed literature on mammographic screening and supplemental screening to inform the society’s 2019 position statement on screening mammography.⁴³

We review the ASBrS recommendations for women at average risk and the underlying supporting evidence as pertain to black women, and we also provide updated recommendations for screening women at higher-than-average risk of breast cancer. We highlight recent data on race-based breast cancer disparities, particularly those impacting black patients and use this data to optimize risk assessment guidelines for Black women. Finally, we highlight basic community outreach and patient navigation strategies to better meet the specific breast cancer risk assessment and screening needs of black women.

Screening Mammography for Women at Average Risk

We continue to endorse ASBrS’s previous recommendation that women of all races with an average risk of breast cancer undergo annual screening mammography beginning at age 40 years. Mammography remains the principal modality of early detection for women at average risk. Despite the limitations of the RCT design, including the ability to test “invitation to screening” rather than the screening itself as the intervention of interest, 11 mammography RCTs demonstrate a collective 22% reduction in breast cancer mortality, corresponding to an estimated 40% reduction in risk of breast cancer-specific mortality for women who undergo screening.^45,49 Likewise, the Cancer Intervention and Surveillance Modeling Network (CISNET) models, commissioned by the USPTF, confirm that annual screening mammography beginning at age 40 years results in a 40% reduction in breast cancer mortality.⁵⁰ More recent evidence that utilizes the incidence rates of fatal breast cancers demonstrated that, with equivalent state-of-the-art treatment, screened women had 60% lower mortality at ten-year follow-up and 47% lower mortality at 20-year follow-up compared with unscreened women.⁵¹

Average-risk women should begin screening at age 40 years, because women screened in their 40s are more likely to have early-stage disease, negative nodes, smaller tumors, and improved disease-free and overall survival compared with their unscreened counterparts.^52,53 Annual mammography is recommended; CISNET models confirm that, compared with biennial screening, annual screening affords greater mortality reduction for all age groups (39.6% reduction for annual screening vs. 23.2% reduction for biennial screening).^50,54 Finally, digital breast tomosynthesis (DBT) is recommended, when available, over two-dimensional (2D) mammography, because it decreases false-positive mammograms while simultaneously increasing cancer detection, although the difference has not always risen to the level of statistical significance.^55,56

Women should continue screening for as long as they maintain good overall health and have a life expectancy of 10 years or greater. Recent analyses of mammographic screening outcomes as a function of age demonstrate that cancer detection rates and positive predictive value for breast biopsy are highest in the over-70 age group, whereas recall rates are lowest, confirming efficacy in this age group.^57,58 Furthermore, older women who forgo screening present with more advanced stage cancers and face worse survival.^48,59–61 CISNET confirms that mammographic screening beyond age 74 years yields benefits of decreased cancer deaths and life-years gained without an upper age limit.⁶² Thus, the available data strongly suggest that the benefits of screening continue with advancing age, whereas the risks of mammography as defined by the USPSTF,⁶³ namely false-positive screening exams and unnecessary biopsies, decrease.

Unfortunately, despite higher breast cancer mortality among black women and higher incidence rates among young black women, there is a paucity of data to optimize screening of this population. The aforementioned RCTs included very few black women, and the CISNET models lack race-specific analyses.⁶⁴ To date, no data support routine mammographic screening for black women before age 40. However, although we recommend annual screening mammography for all women, regardless of race, beginning at age 40, we feel that this recommendation is especially important for black women. Deferring annual screening until age 45 or 50 years, as recommended by the American Cancer Society (ACS)⁶⁵and the USPSTF,⁶⁶ respectively, likely increases race-based breast cancer disparities and disproportionately harms black women.^44,64

Screening Women at Higher-than-Average Risk

In accordance with guidelines from the National Cancer Comprehensive Network (NCCN) and as previously recommended by ASBrS, women at higher-than-average risk of breast cancer include: (1) women with a BRCA gene or other germline mutation known to predispose mutation carriers to high risk of breast cancer or women with very strong family histories of breast cancer who have not undergone complete genetic testing; (2) women with a history of chest or mantle irradiation between the ages of 10 and 30 years; (3) and women with greater than 20% estimated lifetime risk based on an established risk assessment model. This third category includes most women with a history of atypical hyperplasia or lobular carcinoma in situ. These women at higher-than-average risk should undergo annual screening digital breast tomosynthesis (DBT) mammography and contrast-enhanced breast MRI when recommended by their physicians and as part of a plan that reflects shared decision-making. Women with a prior diagnosis of breast cancer and intact breasts also are at higher risk for a recurrent tumor or new primary breast cancer. The ASBrS, the American College of Radiology (ACR), and Society of Breast Imaging (SBI)⁶⁷ support supplemental screening with MRI of women with a personal history of breast cancer and who have dense breasts and/or were younger than age 50 years at diagnosis.

Again, there is a lack of data to evaluate and define higher-than-average breast cancer risk within specific racial and/or ethnic populations, including black women. Thus, to date, we are unable to make specific recommendations for screening higher-than-average risk black women. However, observational data from the Breast Cancer Surveillance Consortium (BCSC) registries indicate that black women at higher-than-average risk tend to undergo screening MRI at lower rates compared with white women.⁶⁸ Furthermore, rates of genetic testing and self-knowledge about mutation carrier status are lower among black women compared with white women, even though rates of BRCA mutations are comparable.⁶⁹ Thus, we must build into our risk mitigation strategies the fact that a higher proportion of black women initially thought to be at average risk are actually at high but unidentified risk of breast cancer and would benefit from early and enhanced (i.e., with MRI in addition to mammogram) screening. In the absence of population-specific research and guidelines, we strongly advise clinicians to meet the risk assessment needs of black women and recommend breast MRI for screening for those who meet the criteria.

Risk Assessment

To determine the appropriate breast cancer screening strategy and age of implementation, ASBrS’s current position statement on screening recommends that all women undergo an initial formal risk assessment at age 25 years or “when first seen by a breast physician or other appropriate health care provider from ages 25-30.” This initial screening should include the following: (1) assessment of family history of malignancies, followed by a discussion with the patient of the need for genetic testing if the patient meets the NCCN guidelines for testing; (2) determination of personal history of atypical hyperplasia and/or lobular carcinoma in situ; (3) documenting prior history of chest or mantle radiation therapy between the ages of 10 and 30 years. If the risk assessment identifies one or more of these risk factors, the woman is considered to be at elevated lifetime risk of breast cancer and warrants higher-risk screening. Per the ASBrS position statement, all women aged 30 years and older also should undergo this same assessment if they have not already done so and an assessment of estimated breast cancer risk utilizing the current Tyrer-Cuzick model or a comparable validated risk model.⁴³

While these recommendations are adequate for most populations, given the younger age at diagnosis and worse prognosis of black women relative to other racial/ethnic groups, the following specific modifications to the recommendations for risk assessment in black women are proposed. First, a recommendation that black women undergo a baseline risk assessment at age 25 years and not later. This assessment should be performed by a breast specialist or other healthcare provider, such as a primary care physician or gynecologist, trained to assess breast cancer risk and who is aware of the increased risks among black women. Additionally, utilizing risk models that incorporate race into the risk assessment is advised.

Most existing risk models were developed and validated in predominantly white populations and are less accurate in predicting risk among other racial populations.^70–75 For example, the original Gail model greatly underestimated the breast cancer risk of black women,^66,76 precluding necessary discussions with clinicians about eligibility for supplemental screening and chemoprevention. In 2015, the initial Gail model, now known as the Breast Cancer Risk Assessment Tool (BCRAT), was finally modified to explicitly account for black race. The revised model more accurately estimates breast cancer risk for black women older than age 30 years.⁷³ Now, both the BCRAT and BCSC models incorporate race.⁷⁷ We strongly advocate for continued efforts to develop and optimize risk assessment tools that better serve diverse populations, including black women. Recent deep learning studies demonstrate marked improvements over traditional models in assessing individual risk across and within diverse patient populations. For example, a recent mammographic imaging-based deep learning model outperformed version 8 of the Tyrer-Cuzick model, and when combined with traditional risk factor information, substantially improved risk discrimination in both white and black women but with an especially pronounced improvement in performance among black women.⁷⁸ Until improved models are validated and widely available, we recommend use of the current BCRAT over BCSC (which may underpredict race in black women)⁷⁷ and other available risk assessment models for risk assessment in black patients.

The goals of these modified recommendations for black women are twofold. The primary goal is to provide earlier risk stratification for black women and deliver more timely supplemental screening when necessary, which is incredibly important given the younger mean age at diagnosis among black women. The second goal is to distinguish this specific population’s elevated risk and needs. Unfortunately, due to a combination of structural and individual racism, many medical providers remain unaware of race-based health disparities, whereas others continue to question their existence.⁷⁹ In addition, many providers are unaware that delaying screening mammography until age 45 or 50 years, as currently recommended by the American Cancer Society⁴⁵ and USPSTF,⁴⁴ respectively, disproportionately harms black women.^63,65 Thus, we also aim to educate healthcare providers and counter provider biases with these assessment modifications.

Given the paucity of data on specific screening benefits, optimal age of initiation, and need for supplemental screening among specific racial and ethnic populations, including black women, there is no strong evidence to support routinely screening black women before age 40 years. Such research is sorely needed. However, by defining black women as a distinct population in need of early, modified risk assessment, we aim to not only define appropriate risk assessment but to distinguish black women as a high-risk group, with the intended secondary effect of increasing clinicians’ recommendations to their black patients’ to begin screening mammography at age 40 years and no later.

Outreach and Patient Navigation

Interventions in both research and clinical care are strongly needed to both guide and deliver breast cancer screening to black women. Optimizing screening of this population must begin with clinical research that accounts for race and social factors. Just as higher recruitment of black patients, currently underrepresented in clinical trials,^80,81 is necessary to better understand how race and modifiable social factors may drive disease, imaging trials also must actively recruit black patients. The aforementioned 11 RCT screening mammography trials grossly underrecruited black women.⁸² Their suboptimal inclusion represents a significant missed opportunity to study and guide appropriate screening for non-white populations in general and black women in particular. Because of the large number of subjects, the high cost of such trials, and now routine use of screening mammography in the United States, new RCTs to include more diverse populations are unlikely to occur.

CHALLENGES FOR THE FUTURE

As we design future imaging trials, we must place greater emphasis on diverse recruitment and accrual. - Doing so requires commitment by research investigators and institutions to studying diverse populations and an itemization of definitive strategies to achieve study diversity. For example, in addition to defining target population accrual goals, such trials should utilize resources for collection of subject demographic and psychosocial data as well as real-time tracking of these variables to ensure sufficient accrual of black patients.^83,84 Likewise, future research must investigate the effects of social variables beyond race, such as poverty, education, access to care, health insurance coverage, geography, and language barriers related to English proficiency and patient literacy on breast cancer clinical outcomes.^83,85

Finally, interventions within healthcare systems and communities are necessary to directly target black women for timely risk assessment and screening. Further research is needed to identify and evaluate strategies to overcome clinician biases and effect necessary clinical practice changes. Concerted efforts between health systems and communities and neighborhoods with target patient populations must utilize an integrated network of nurse coordinators, patient navigators, and community-outreach teams. Models of successful cancer screening programs for black patients should be further studied and optimized for use in other populations. For example, the Comprehensive Colorectal Cancer Initiative in Delaware synthesized efforts from a trained nurse navigator with specialized outreach efforts to the local black communities and covered screening and treatment costs for uninsured patients. The program successfully eliminated disparities in colorectal cancer screening and equalized incidence rates within 8 years of initiation.⁸⁶ In addition, the mortality gap was nearly eliminated, with a 42% mortality decline among black patients compared with 13% among white patients.^86,87 Likewise, in breast cancer, we have an opportunity to improve risk assessment and access to high-quality screening to redress both short-term disparities in breast cancer diagnosis and long-term disparities in breast cancer outcomes among black women and other diverse patients.