Disparities in Breast Cancer Treatment and Outcomes: Biological, Social, and Health System Determinants and Opportunities for Research

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Abstract

Racial disparities in breast cancer mortality have been widely documented for several decades and persist despite advances in receipt of mammography across racial groups. This persistence leads to questions about the roles of biological, social, and health system determinants of poor outcomes. Cancer outcomes are a function not only of innate biological factors but also of modifiable characteristics of individual behavior and decision making as well as characteristics of patient-health system interaction and the health system itself. Attempts to explain persistent racial disparities have mostly been limited to discussion of differences in insurance coverage, socioeconomic status, tumor stage at diagnosis, comorbidity, and molecular subtype of the tumor. This article summarizes existing literature exploring reasons for racial disparities in breast cancer mortality, with an emphasis on treatment disparities and opportunities for future research. Because breast cancer care requires a high degree of multidisciplinary team collaboration, ensuring that guideline recommended treatment (such as endocrine therapy for hormone receptor positive patients) is received by all racial/ethnic groups is critical and requires coordination across multiple providers and health care settings. Recognition that variation in cancer care quality may be correlated with race (and socioeconomic and health system factors) may assist policy makers in identifying strategies to more equally distribute clinical expertise and health infrastructure across multiple user populations.

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Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.

Lisa A Carey, Charles Perou, Chad A Livasy … (2006)

Gene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER-), luminal A, and luminal B. To determine population-based distributions and clinical associations for breast cancer subtypes. Immunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified (negative for all 5 markers). We examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer-specific survival. The basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER- subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer-specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER- and basal-like subtypes. Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non-African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.

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Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer.

Dawn L Hershman, Theresa Shao, Lawrence H Kushi … (2011)

Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was ≥80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95% CI 1.23-1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.

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Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.

Kirsty O’Brien, Mariko L Carey, Robert Millikan … (2010)

Previous research identified differences in breast cancer-specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2(+)/ER(-)). We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Cancer subtypes luminal A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer-specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0). Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. ©2010 AACR.