Date Published: January 13, 2017
Publisher: Public Library of Science
Author(s): Nikita Wright, Jun Xia, Guilherme Cantuaria, Sergey Klimov, Mildred Jones, Pranay Neema, Dora Il’yasova, Uma Krishnamurti, Xiaoxian Li, Michelle D. Reid, Meenakshi Gupta, Padmashree C. G. Rida, Remus Osan, Ritu Aneja, William B. Coleman.
Clinical studies have revealed a higher risk of breast tumor recurrence in African-American (AA) patients compared to European-American (EA) patients, contributing to the alarming inequality in clinical outcomes among the ethnic groups. However, distinctions in recurrence patterns upon receiving hormone, radiation, and/or chemotherapy between the races remain poorly characterized.
We compared patterns and rates (per 1000 cancer patients per 1 year) of recurrence following each form of treatment between AA (n = 1850) and EA breast cancer patients (n = 7931) from a cohort of patients (n = 10504) treated between 2005–2015 at Northside Hospital in Atlanta, GA.
Among patients who received any combination of adjuvant therapy, AA displayed higher overall rates of recurrence than EA (p = 0.015; HR: 1.699; CI: 1.108–2.606). Furthermore, recurrence rates were higher in AA than EA among stage I (p = 0.031; HR: 1.736; CI: 1.052–2.864) and T1 classified patients (p = 0.003; HR: 2.009; CI: 1.263–3.197). Interestingly, among patients who received neoadjuvant chemotherapy, AA displayed higher rates of local recurrence than EA (p = 0.024; HR: 7.134; CI: 1.295–39.313).
Our analysis revealed higher incidence rates of recurrence in AA compared to EA among patients that received any combination of adjuvant therapy. Moreover, our data demonstrates an increased risk of tumor recurrence in AA than EA among patients diagnosed with minimally invasive disease. This is the first clinical study to suggest that neoadjuvant chemotherapy improves breast cancer recurrence rates and patterns in AA.
The significant divide in breast cancer mortality between African-American (AA) and European-American (EA) patients remains a challenge for clinicians. Despite a similar number of reported incidences of breast cancer among AA and EA women, AAs experience notably higher severity in clinical outcomes and exhibit a 40% higher death rate than EAs among premenopausal and menopausal breast cancer patients [1–3]. Recurrent breast cancer has impeded successful management of the disease for decades and is one of the primary factors for this racial division in prognosis . Statistics demonstrate that approximately 40% of all breast cancer survivors will experience a recurrence episode during their lifetime, which has been suggested to play a principal role in breast cancer mortality [4, 5]. Clinical studies have revealed a higher risk of recurrence in AA compared to EA, presumably contributing to the inequality in clinical outcomes among the ethnic groups . This statistic has provided an impetus for clinicians to devise and implement robust prognosticative measures to preclude the tumor returning in AA breast cancer patients. However, distinctions in recurrence rates and patterns following various forms of treatment between the races have not been thoroughly evaluated. This warrants more investigation to potentially attenuate the observed racial disparity in recurrence in the clinic. Hence, we conducted a large institutional study based in Atlanta, Georgia, in which we analyzed rates and patterns of tumor recurrence post hormone, radiation, and chemotherapy among AA and EA breast cancer patients. This retrospective clinical study uncovered previously unrecognized distinctions in recurrence patterns following each conventional form of treatment among racially distinct breast populations and may impart valuable clinical insight into preclusive measures for mitigating the ethnic disparity in breast tumor recurrence.
This clinical study is the first extensive investigation into the rates and patterns of tumor recurrence in breast cancer patients following conventional treatments among racially distinct populations. Our study has revealed notable distinctions in recurrence patterns among EA and AA patients. First, AA displayed considerably higher rates of recurrence than EA (Tables 1 and 2). Second, we observed higher severity in recurrence patterns displayed by AA for whom we discerned stronger trends in AA of the tumor recurrence to regional and distant sites (Tables 1 and 2). This trend was evident after patients received radiation, hormone, and any combination of adjuvant therapies. Overall, these observed trends were quite significant since local recurrence tends to elicit a more favorable clinical prognosis compared to distant recurrence, while the latter trends type precedes a poorer clinical prognosis. Triple negative breast cancer (TNBC) patients have been shown to display an increased risk for recurrence and particularly for tumor reocurrence to distant sites, while non-TNBC patients exhibit higher trends of the tumor reappearing in local sites [1,17]. These findings parallel our observations of an increased risk of overall and especially distant recurrence in AA, as well as an increased risk of local recurrences in EA. This tendency reflects the well-reported higher incidence of TNBC phenotypes in AA patients and a higher prevalence of non-TNBC subtypes in EA patients [18,19]. Furthermore, we observed a trend of a higher number of recurrence episodes in AA compared to EA. Additionally, we discerned stronger inclinations of distant recurrence to multiple organs in AA compared to EA. These observed aggressive recurrence patterns reveal that AA patients exhibit an increased prospect of a poor clinical prognosis, theoretically contributing to their higher mortality rates than EA patients. Recurrence rates were also found to be higher in AA than EA among early stage, minimally invasive breast cancer patients (Table 3). This data presents an intriguing paradox as advanced stage upon diagnosis is typically associated with increased risk for recurrence [19–22]. Thus, these findings suggest that AA patients of all clinical stages should be closely evaluated for the prospect of tumor recurrence. Neoadjuvant chemotherapy seemed to reverse these observed recurrence trends (Table 2). Among patients who received neoadjuvant chemotherapy, AA displayed a lower rate of recurrence than EA; however due to a low number of recorded patients that received neoadjuvant chemotherapy, statistical significance was diminished. In addition, higher incidences of aggressive recurrence patterns in AA were notably attenuated after these patients underwent neoadjuvant chemotherapy. This data suggest preoperative chemotherapy may reduce the severity of recurrence rates and patterns in AA patients. This study suggests that neoadjuvant chemotherapy should be recommended for AA patients who are at higher risk for developing recurrence. A recent clinical study reported that in fact, neoadjuvant chemotherapy is administered more frequently to AA than EA patients likely as a result of their higher prevalence of advanced stage, grade, and triple negative receptor status upon presentation .