Key Points
Question
Are there differences in locoregional recurrence by race and ethnicity among patients with hormone receptor–positive, node-negative, early-stage breast cancer?
Findings
In this post hoc analysis of 9369 randomized clinical trial participants, 8-year rates of breast cancer locoregional recurrence were highest among Asian and non-Hispanic Black women (4%) compared with Hispanic (3%) and non-Hispanic White women (2%). In adjusted analyses, Asian and non-Hispanic Black race and ethnicity were associated with an 80% to 90% increase in locoregional recurrence.
Meaning
These findings suggest that racial and ethnic differences in locoregional recurrence patterns are prevalent even in a clinical trial population with similar access to care.
This post hoc analysis examines racial and ethnic disparities in locoregional recurrence among patients with hormone receptor–positive, node-negative, early-stage breast cancer enrolled in the TAILORx randomized clinical trial.
Abstract
Importance
Whether racial and ethnic disparities in locoregional recurrence (LRR) exist among patients with similar access to care treated in randomized clinical trials is unknown.
Objective
To examine racial and ethnic differences in LRR among patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])–negative, node-negative breast cancer enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx).
Design, Setting, and Participants
This unplanned retrospective post hoc analysis examined a prospective multicenter clinical trial population of women with breast cancer enrolled between 2006 and 2010, with 9 years of follow-up. The TAILORx investigators randomized patients to treatment based on their Oncotype DX recurrence score, including endocrine therapy alone (recurrence score <11), endocrine therapy alone vs chemotherapy followed by endocrine therapy (recurrence score 11-25), or chemotherapy followed by endocrine therapy (recurrence score >25). Patients with unknown race and ethnicity or lack of follow-up were excluded from this analysis. Data analysis was performed between December 2021 and March 2022.
Main Outcome and Measures
Locoregional recurrence was defined as ipsilateral in breast, skin, chest wall, or regional nodal recurrence without concurrent distant recurrence, and was stratified by racial and ethnic group. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards regression models were used for survival analyses.
Results
Of the 10 273 women enrolled in TAILORx, this analysis included 9369 with T1-2N0 HR-positive, ERBB2-negative breast cancer. Of these patients, 428 (4.6%) were Asian, 886 (9.4%) were Hispanic, 676 (7.2%) were non-Hispanic Black (hereinafter Black), and 7406 (78.8%) were non-Hispanic White (hereinafter White). Assigned treatment receipt was high, with a 9.3% (n = 870) crossover of treatment groups and a median endocrine therapy duration of longer than 60 months, ranging from 61.1 to 65.9 months, across racial and ethnic groups. A total of 6818 patients (72.6%) received radiation (6474 [96.1%] after breast-conserving surgery and 344 [13.0%] after mastectomy). At a median follow-up of 94.8 months (range, 1-138 months), 8-year LRR rates were 3.6% (95% CI, 1.6%-5.6%) in Asian patients, 3.9% (95% CI, 2.2%-5.4%) in Black patients, 3.1% in Hispanic patients (95% CI, 1.7%-4.5%), and 1.8% (95% CI, 1.5%-2.3%) in White patients (P < .001). In survival analyses adjusted for patient, tumor, and treatment factors, Asian race (hazard ratio, 1.91 [95% CI, 1.12-3.29]) and Black race (1.78 [1.15-2.77]) were independently associated with LRR. In adjusted survival analyses for breast cancer mortality, LRR was independently associated with increased breast cancer mortality (hazard ratio, 5.71 [95% CI, 3.50-9.31]).
Conclusions and Relevance
In this post hoc analysis, racial and ethnic differences in LRR were observed among patients with T1-2N0 HR-positive, ERBB2-negative breast cancer despite high rates of treatment receipt in this clinical trial population, with the highest LRR rates in Asian and Black patients. Further study is needed to understand whether failure to rescue after LRR may contribute to racial disparities in breast cancer mortality.
Trial Registration
ClinicalTrials.gov Identifier: NCT00310180
Introduction
Across population-based studies in the US, non-Hispanic Black women consistently have worse survival outcomes compared with non-Hispanic White women, even after adjustment for available confounders and tumor characteristics.1,2,3,4,5 Despite substantial attention to disparate outcomes by race and ethnicity and improvements in breast cancer treatments, minimal progress has been made in closing the gaps in breast cancer outcomes, with Black women continuing to have 39% higher breast cancer mortality (BCM) compared with White women over time.6
Studies have suggested that stage at diagnosis accounts for at least 25% of the excess mortality among Black women,1 and additional confounders including comorbidities, tumor characteristics, and treatment receipt account for up to 75% of excess mortality.5 However, disparate outcomes in mortality by race and ethnicity continue to be seen even among patients with early-stage breast cancer enrolled and treated in clinical trials where treatment receipt is tightly controlled.7,8,9 In addition to the importance of access to care and timely treatment contributing to these disparities,10,11,12,13,14 social determinants of health are likely important confounders that are challenging to study in large registries and may affect acceptance of and adherence to recommended treatments.15,16,17
Although it is known that a locoregional recurrence (LRR) after treatment for breast cancer is associated with increased BCM,18,19,20 it is unclear whether racial and ethnic differences in LRR may contribute to disparate survival outcomes. This study was undertaken with the objective of examining differences in LRR by race and ethnicity in a modern cohort of women with early-stage breast cancer treated in the Trial Assigning Individualized Options for Treatment (TAILORx), a large prospective randomized clinical trial.
Methods
Data for this post hoc analysis were obtained with permission through the National Clinical Trials Network data archive. Secondary data use was approved by the Brigham and Women’s Hospital Institutional Review Board. Informed consent for trial participation was obtained from all participants in the original TAILORx clinical trial population; additional consent was waived for the secondary analysis of the deidentified data set. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Data Source
TAILORx was a multicenter randomized clinical trial that enrolled women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])–negative, node-negative breast cancer with tumors up to 5 cm (T1-2N0) between 2006 and 2010. Oncotype DX recurrence score results were used to assign treatment, including endocrine therapy alone (recurrence score <11), endocrine therapy alone vs chemotherapy followed by endocrine therapy (recurrence score 11-25), or chemotherapy followed by endocrine therapy (recurrence score >25). Full details of the trial protocol and end points are described in the initial trial reports and in Supplement 1.21,22,23
Of the 10 273 patients enrolled in TAILORx, the following were excluded from this study: 323 with unknown race and ethnicity, 216 with tumor characteristics outside of the trial inclusion criteria (177 had unknown HR status and 39 had T3 tumors), and 338 without any follow-up. Therefore, 9396 patients were included in this post hoc analysis (Figure 1). Available variables included race and ethnicity, age (≤50 or >50 years), tumor size (T1 or T2), grade (1, 2, 3, or unknown), estrogen or progesterone receptor status, recurrence score result (<11, 11-25, or >25), breast surgery type (breast-conserving surgery [BCS] or mastectomy), treatment assignment and crossover, chemotherapy receipt and regimen, radiation receipt, endocrine therapy type and duration, first breast cancer–related event type (ipsilateral breast recurrence, recurrence at locoregional site, distant recurrence, new contralateral breast cancer, new second primary cancer, or death without breast cancer event), and follow-up time. Race and ethnicity were determined using a combination of self-reported race (American Indian or Alaska Native, Asian, Black, Native Hawaiian or other Pacific Islander, White, multiple, or unknown) and self-reported ethnicity (Hispanic, non-Hispanic, or unknown) and recategorized as Asian, Hispanic, non-Hispanic Black (hereinafter Black), or non-Hispanic White (hereinafter White). Overall, 32 patients identifying as Native Hawaiian or other Pacific Islander were grouped as Asian, and 35 patients identifying as American Indian or Alaska Native and 9 patients identifying as multiracial were excluded for the purposes of this analysis owing to the small sample size.
Figure 1. Study Flow Diagram.
HR indicates hormone receptor; RS, recurrence score.
Statistical Analysis
The study design was an unplanned retrospective analysis of a prospective clinical trial data set. The primary end point was LRR, which was defined as ipsilateral in breast, skin, chest wall, or regional nodal recurrence without concurrent distant recurrence. Contralateral breast cancer was not considered an LRR event. Follow-up data were collected from the time of randomization or registration to time of event or last follow-up. Patients were censored at the time of a non-LRR event. A secondary end point was BCM, defined as death from breast cancer; patients were censored at the time of a nonbreast cancer–related death.
Descriptive statistics were used to compare patient, tumor, and treatment characteristics by racial and ethnic group. Kaplan-Meier hazard curves were used to estimate 8-year LRR by race and ethnicity and were further stratified by recurrence score category and breast surgery type. Cox proportional hazards regression analysis was used to identify associations with LRR and BCM. Covariates in both models included race and ethnicity, age, tumor size, tumor grade, HR status, recurrence score category, breast surgery type, radiation therapy, chemotherapy, treatment crossover, and endocrine therapy duration. Locoregional recurrence was incorporated as a covariate in the BCM model. Hazard ratios greater than 1 suggested a higher hazard of LRR or BCM. All CIs are reported at a 95% level of significance. All P values were 2 sided and P < .05 was considered statistically significant. SPSS, version 28 (IBM SPSS), was used for all analyses. Data analysis was performed between December 2021 and March 2022.
Results
Cohort Characteristics
A total of 9396 women with T1-2N0 HR-positive, ERBB2-negative breast cancer enrolled in TAILORx were included in this analysis. Of these patients, 428 (4.6%) were Asian, 676 (7.2%) were Black, 886 (9.4%) were Hispanic, and 7406 (78.8%) were White. Compared with White patients, other racial and ethnic minority patients were younger and had larger and higher-grade tumors (Table 1). Black and Hispanic patients had a higher proportion of recurrence scores greater than 25 (113 [16.7%] and 153 [17.3%] vs 1031 White patients [13.9%]); Asian patients had the highest proportion of recurrence scores below 11 (80 [20.8%] vs 1229 White patients [16.6%]; P = .008).
Table 1. Cohort Characteristics and Treatment Receipt by Race and Ethnicitya.
| Characteristic | Patient groupb (N = 9396) | P value | |||
|---|---|---|---|---|---|
| Asianc (n = 428) | Hispanic (n = 886) | Non-Hispanic Black (n = 676) | Non-Hispanic White (n = 7406) | ||
| Age, y | |||||
| Median (range) | 52 (29-75) | 54 (23-77) | 54 (27-87) | 56 (23-89) | <.001 |
| ≤50 | 159 (37.1) | 305 (34.4) | 232 (34.3) | 1864 (25.2) | <.001 |
| >50 | 269 (62.9) | 581 (65.6) | 444 (65.7) | 5542 (74.8) | |
| Pathologic tumor stage | |||||
| pT1 | 285 (66.6) | 587 (66.3) | 425 (62.9) | 5182 (70.0) | <.001 |
| pT2 | 143 (33.4) | 299 (33.7) | 251 (37.1) | 2224 (30.0) | |
| Tumor grade | |||||
| 1 | 111 (25.9) | 196 (22.1) | 147 (21.7) | 1992 (26.9) | <.001 |
| 2 | 225 (52.6) | 484 (54.6) | 345 (51.0) | 4000 (54.0) | |
| 3 | 79 (18.5) | 163 (18.4) | 156 (23.1) | 1214 (16.4) | |
| Unknown | 13 (3.0) | 43 (4.9) | 28 (4.1) | 200 (2.7) | |
| Hormone receptor status | |||||
| ER+, PR+ | 381 (89.0) | 765 (86.3) | 569 (84.2) | 6532 (88.2) | <.001 |
| ER+, PR− | 38 (8.9) | 104 (11.7) | 95 (14.1) | 685 (9.2) | |
| ER−, PR+ | 2 (0.5) | 8 (0.9) | 7 (1.0) | 37 (0.5) | |
| ER+, PR unknown | 7 (1.6) | 9 (1.0) | 5 (0.7) | 152 (2.1) | |
| Recurrence score | |||||
| Median (range) | 17 (0-59) | 17 (0-87) | 17 (0-69) | 17 (0-81) | .006 |
| <11 | 80 (20.8) | 149 (16.8) | 104 (15.4) | 1229 (16.6) | .008 |
| 11-25 | 288 (67.3) | 584 (65.9) | 459 (67.9) | 5146 (69.5) | |
| >25 | 51 (11.9) | 153 (17.3) | 113 (16.7) | 1031 (13.9) | |
| Surgery | |||||
| BCS | 300 (70.1) | 632 (71.3) | 467 (69.1) | 5341 (72.1) | .32 |
| Mastectomy | 128 (29.9) | 254 (28.7) | 209 (30.9) | 2065 (27.9) | |
| Radiation therapy after BCS | |||||
| Yes | 288 (96.0) | 611 (96.7) | 448 (95.9) | 5127 (96.0) | .87 |
| None | 12 (4.0) | 21 (3.3) | 19 (4.1) | 214 (4.0) | |
| Postmastectomy radiation therapy | |||||
| Yes | 15 (11.7) | 58 (22.8) | 26 (12.4) | 245 (11.9) | <.001 |
| No | 113 (88.3) | 196 (77.2) | 183 (87.6) | 1820 (88.1) | |
| Treatment group crossoverd | |||||
| Yes | 42 (9.8) | 70 (7.9) | 65 (9.6) | 693 (9.4) | .52 |
| No | 386 (90.2) | 816 (92.1) | 611 (90.4) | 6713 (90.6) | |
| Chemotherapy | |||||
| Yes | 172 (40.2) | 438 (49.4) | 295 (43.6) | 3139 (42.4) | <.001 |
| No | 256 (59.8) | 448 (50.6) | 381 (56.4) | 4267 (57.6) | |
| Endocrine therapy duration, y | |||||
| <3 | 38 (8.9) | 130 (14.7) | 113 (16.7) | 1062 (14.3) | .001 |
| 3-5 | 101 (23.6) | 237 (26.7) | 140 (20.7) | 1846 (24.9) | |
| ≥5 | 289 (67.5) | 519 (58.6) | 423 (62.6) | 4498 (60.7) | |
| Median (range), mo | 65.9 (0.2-131.6) | 61.1 (0-120.4) | 63.8 (0-134.2) | 62.3 (0-132.7) | <.001 |
| LRR | |||||
| Any LRR | 15 (3.5) | 21 (2.4) | 24 (3.6) | 133 (1.8) | .002 |
| After BCS | 9/300 (3.0) | 15/632 (2.4) | 13/467 (2.8) | 89/5341 (1.7) | .10 |
| After mastectomy | 6/128 (4.7) | 6/254 (2.4) | 11/209 (5.3) | 44/2065 (2.1) | .02 |
Abbreviations: BCS, breast-conserving surgery; ER, estrogen receptor; LRR, locoregional recurrence; PR, progesterone receptor.
Unless noted otherwise, data are presented as No. (%) of patients.
Patients who were American Indian or Alaska Native (n = 35) and multiracial (n = 9) were excluded owing to the small sample size.
Including 32 patients who were Native Hawaiian or Other Pacific Islander.
Treatment crossover refers to chemotherapy assignment or randomization.
Treatment Receipt
Treatment receipt and adherence is outlined in Table 1. Most patients were treated with BCS and radiation therapy without differences across racial and ethnic groups. Hispanic patients were more likely to receive radiation therapy after mastectomy compared with White patients (58 [22.8%] vs 245 [11.9%]; P < .001). Acceptance of assigned and/or randomized treatment was high, with only 870 patients (9.3%) having crossover in treatment groups. The rate of crossover was similar across racial and ethnic groups. A total of 6818 patients (72.6%) received radiation (6474 [96.1%] after BCS and 344 [13.0%] after mastectomy). The median endocrine therapy duration was longer than 60 months, ranging from 61.1 to 65.9 months, across all racial and ethnic groups, with Asian and Black patients having the highest rates of endocrine therapy duration of 5 years or longer (289 [67.5%] and 423 [62.6%] vs 4498 White patients [60.7%]; P < .001).
When stratified by surgery type, patients treated with mastectomy vs BCS were younger (820 [30.9%] vs 1740 [25.8%] aged ≤50 years; P < .001), had more T2 tumors (1071 [40.3%] vs 1846 [24.4%]), and were less likely to have 5 years of endocrine therapy or longer (1549 [58.3%] vs 4180 [62.0%]) (eTable 1 in Supplement 2). Among patients treated with mastectomy, characteristics and treatment were similar across racial and ethnic groups, although White patients were less likely to be aged 50 years or younger (592 [28.7%]) compared with Asian (47 [36.7%]), Black (80 [38.3%]), and Hispanic (101 [39.8%]) patients (P < .001) (eTable 2 in Supplement 2).
Locoregional Recurrence by Race and Ethnicity
The median follow-up was 94.8 months (range, 1-138 months). The 8-year probability of LRR differed by racial and ethnic groups, with LRR rates of 3.6% (95% CI, 1.6%-5.6%) in Asian patients, 3.9% (95% CI, 2.2%-5.4%) in Black patients, 3.1% in Hispanic patients (95% CI, 1.7%-4.5%), and 1.8% (95% CI, 1.5%-2.3%) in White patients (P < .001) (Figure 2). Analysis stratified by recurrence score category indicated that Black patients had the highest probability of 8-year LRR in the group with recurrence scores of 11 to 25 compared with White patients (5.1% vs 1.8%; P < .001); Asian patients had the highest 8-year LRR probability in the group with recurrence scores greater than 25 compared with White patients (10.6% vs 3.0%; P = .026) (Figure 3A-C). In analysis stratified by surgery type, 8-year LRR probability was highest among Asian and Black patients after mastectomy compared with White patients (6.3% and 6.4% vs 2.4%; P = .009) (Figure 3D and E).
Figure 2. Kaplan-Meier Locoregional Recurrence (LRR) Hazard Curves by Race and Ethnicity.
The dashed line indicates the median follow-up.
Figure 3. Kaplan-Meier Locoregional Recurrence (LRR) Hazard Curves by Race and Ethnicity Stratified by Recurrence Score and Breast Surgery Type.
A to C, Patient subgroups with a recurrence score of less than 11 (A), 11 to 25 (B), or greater than 25 (C). D and E, Patients treated with breast-conserving surgery (D) or mastectomy (E). Dotted vertical lines indicate the median follow-up.
Adjusted Cox proportional hazards regression analysis of LRR adjusting for patient demographics, clinical features, and treatment factors suggested that compared with White race, Asian race (hazard ratio, 1.91 [95% CI, 1.12-3.29]) and Black race (1.78 [1.15-2.77]) were independently associated with increased risk of LRR. Additional factors associated with LRR included age younger than 50 years (hazard ratio, 1.78 [95% CI, 1.15-2.77]), higher tumor grade (2.21 [1.39-3.53] for grade 3), and higher recurrence score category (2.77 [1.42-5.42] for score >25). There was no association of treatment factors including endocrine therapy and radiation therapy with LRR; chemotherapy receipt was associated with a small decrease in LRR (hazard ratio, 0.71 [95% CI, 0.51-1.00]) (Table 2).
Table 2. Adjusted Cox Proportional Hazards Regression Model of Locoregional Recurrence (LRR) and Breast Cancer Mortality (BCM).
| Survival measure | LRR | BCM | ||
|---|---|---|---|---|
| Hazard ratio (95% CI) | P value | Hazard ratio (95% CI) | P value | |
| LRR | ||||
| Yes | NA | NA | 5.71 (3.50-9.31) | <.001 |
| No | NA | NA | 1 [Reference] | NA |
| Race and ethnicity | ||||
| Asian | 1.91 (1.12-3.29) | .02 | 0.81 (0.33-1.99) | .64 |
| Hispanic | 1.51 (0.95-2.40) | .08 | 0.21 (0.07-0.65) | .007 |
| Non-Hispanic Black | 1.78 (1.15-2.77) | .01 | 1.50 (0.93-2.42) | .09 |
| Non-Hispanic White | 1 [Reference] | NA | 1 [Reference] | NA |
| Age, y | ||||
| ≤50 | 1.78 (1.33-2.38) | <.001 | 0.88 (0.62-1.25) | .48 |
| >50 | 1 [Reference] | NA | 1 [Reference] | NA |
| Pathologic tumor | ||||
| pT1 | 1 [Reference] | NA | 1 [Reference] | NA |
| pT2 | 1.52 (1.14-2.04) | .005 | 2.10 (1.53-2.89) | <.001 |
| Tumor grade | ||||
| 1 | 1 [Reference] | NA | 1 [Reference] | NA |
| 2 | 1.54 (1.04-2.29) | .03 | 2.43 (1.39-4.23) | <.001 |
| 3 | 2.21 (1.39-3.53) | <.001 | 4.26 (2.34-7.74) | <.001 |
| Unknown | 1.26 (0.49-3.24) | .63 | 7.31 (3.44-15.5) | <.001 |
| HR status | ||||
| ER+, PR+ | 1 [Reference] | NA | 1 [Reference] | NA |
| ER+, PR− | 1.07 (0.67-1.73) | .77 | 1.27 (0.82-1.96) | .29 |
| ER−, PR+ | 1.50 (0.36-6.21) | .57 | 1.12 (0.27-4.60) | .88 |
| ER+, PR unknown | 0.69 (0.17-2.80) | .62 | 2.57 (0.94-7.03) | .07 |
| Recurrence score | ||||
| <11 | 1 [Reference] | NA | 1 [Reference] | NA |
| 11-25 | 1.71 (1.05-2.81) | .33 | 4.50 (1.79-11.41) | .001 |
| >25 | 2.77 (1.42-5.42) | .003 | 6.27 (2.25-17.5) | <.001 |
| Surgery | ||||
| BCS | 1 [Reference] | NA | 1 [Reference] | NA |
| Mastectomy | 0.81 (0.46-1.44) | .47 | 0.75 (0.41-1.38) | .35 |
| Radiation therapy | ||||
| Yes | 0.60 (0.34-1.06) | .08 | 0.59 (0.32-1.08) | .08 |
| No | 1 [Reference] | NA | 1 [Reference] | NA |
| Chemotherapy | ||||
| Yes | 0.71 (0.51-1.00) | .047 | 1.72 (1.19-2.49) | .004 |
| No | 1 [Reference] | NA | 1 [Reference] | NA |
| Treatment crossover | ||||
| Yes | 0.69 (0.45-1.07) | .10 | 0.86 (0.51-1.46) | .58 |
| No | 1 [Reference] | NA | 1 [Reference] | NA |
| Endocrine therapy duration, y | ||||
| <3 | 1.45 (0.94-2.23) | .09 | 15.6 (10.6-23.0) | <.001 |
| 3-5 | 0.90 (0.63-1.29) | .55 | 3.80 (2.53-5.72) | <.001 |
| ≥5 | 1 [Reference] | NA | 1 [Reference] | NA |
Abbreviations: BCM, breast cancer mortality; ER, estrogen receptor; HR, hormone receptor; NA, not applicable; PR, progesterone receptor.
In adjusted Cox proportional hazards regression analysis of BCM, LRR was associated with a more than 5-fold likelihood of BCM (hazard ratio, 5.71 [95% CI, 3.50-9.31]). Compared with White patients, Asian and Black patients did not have a statistically different risk of BCM (hazard ratio, 0.81 [95% CI, 0.33-1.99] and 1.50 [0.93-2.42]). However, Hispanic patients had a lower risk of BCM (hazard ratio, 0.21 [95% CI, 0.07-0.65]). Factors associated with increased BCM risk included larger tumor size (hazard ratio, 2.10 [95% CI, 1.53-2.89] for T2), higher tumor grade (4.26 [2.34-7.74] for grade 3), higher recurrence score (6.27 [2.25-17.5] for score >25), chemotherapy receipt (1.72 [1.19-2.49]), and decreased endocrine therapy duration (15.6 [10.6-23.0] for <3 years) (Table 2).
Discussion
Although previous analyses have shown poorer survival among Black patients enrolled in TAILORx,8 racial and ethnic differences in LRR have not been previously described in this clinical trial population. In this analysis of LRR patterns among 9363 patients with T1-2N0 HR-positive, ERBB2-negative breast cancer enrolled in TAILORx with high rates of treatment receipt and adherence across racial and ethnic groups, Asian and Black patients had rates of LRR approximately twice that of White patients. Adjusted analyses suggested that in addition to tumor characteristics, Asian race and Black race were independently associated with LRR. Interestingly, Asian race and Black race were also associated with the highest rates of LRR after mastectomy and among patients with a recurrence score of 11 or greater.
Previous work exploring LRR patterns by race and ethnicity comes from older or single-institutional series. Two institutional studies of patients treated at Fox Chase Cancer Center (1977-1985) and Memorial Sloan Kettering Cancer Center (1998-2007) reported increased rates of regional recurrence (although not local recurrence) among Black patients compared with White patients.24,25 A study of 281 patients with stage I to III breast cancer treated at the University of Kansas (1992-1998) reported less favorable patterns of local recurrence among Black women, with more skin and multicentric in-breast recurrences.26 The current study focuses on a large multi-institutional contemporary cohort of patients with HR-positive, ERBB2-negative, early-stage breast cancer with findings of increased LRR among Asian and Black patients in this population. Rates of LRR were higher particularly after mastectomy despite similar tumor and treatment characteristics across racial and ethnic groups, suggesting that Asian and Black patients may have worse patterns of local recurrence. An increasing recurrence score was associated with increasing LRR in general; however, no differences in LRR by race or ethnicity were observed in the group with lower recurrence scores (<11), and Asian but not Black patients had increased LRR in the group with higher recurrence scores (>25). It is not clear why these trends are not consistent across groups; however, it is noted that there are small numbers of events in these recurrence score category groups, so these analyses should be interpreted with caution. Importantly, this is a clinical trial population with high rates of treatment acceptance (9.3% crossover of treatment groups) and treatment receipt and duration across racial and ethnic groups. As such, it is likely that disparities in LRR in the general population might be even wider when considering broader disparities in access, timeliness, and adherence to treatment outside of a clinical trial.12,13,14,15,16,17
Locoregional recurrence is associated with increased BCM. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses of 10 801 women treated with BCS in 17 randomized clinical trials and 8135 women treated with mastectomy in 22 randomized clinical trials demonstrated that reducing the risk of LRR by adding radiation therapy translated into decreased BCM.19,20 In a study of 363 Black women with stage I to III breast cancer treated at The University of Texas MD Anderson Cancer Center (1975-1994), LRR was associated with substantially decreased overall survival after either BCS or mastectomy.27 A pooled analysis of patients with node-negative breast cancer treated on 5 National Surgical Adjuvant Breast and Bowel Project protocols (1980s to early 2000s) found LRR to be associated with mortality; this was true for in-breast tumor recurrence (hazard ratios, 2.3 and 4.5 for HR-positive and HR-negative disease) and other LRR (hazard ratios, 6.4 and 19.8 for HR-positive and HR-negative disease); Black race was also independently associated with increased mortality.18 In the current study, LRR was independently associated with BCM in the TAILORx population; although race and ethnicity was not associated with BCM in this clinical trial population, increased LRR among Black patients may be clinically significant and suggests a possible contributor toward disparate BCM in the US population. Further work is needed to understand patterns of LRR in other breast cancer subtypes and in other clinical populations.
Notably, although both Asian and Black women had increased LRR in this study, most studies suggest that Black patients have increased BCM and Asian patients have decreased BCM compared with White patients with breast cancer.4,6 Further, while Hispanic ethnicity was not associated with LRR in this study, it was associated with decreased BCM. Previous analyses of TAILORx have additionally shown that endocrine therapy duration was similar across racial groups and poorer survival among Black women was not explained by socioeconomic factors.8,28 These inconsistencies highlight the importance of unmeasured societal factors that likely contribute to disparate breast cancer survival outcomes, including differential effects of social determinants of health, social stressors, and widespread systemic inequalities and racism in our society.29,30,31 Additionally, failure to rescue after occurrence of LRR in Black patients may disproportionately play a role in future breast cancer events and ultimately death; this could be a potential point of future study and intervention to help reduce the BCM gap.
Strengths of this study include the use of a large multi-institutional prospective clinical trial population of patients with early-stage breast cancer presenting with similar access to care, disease characteristics, treatment, and adherence, which provides a robust comprehensive data source with accurate long-term outcome measures and decreases bias between groups.
Limitations
Limitations of this study include the underrepresentation of racial and ethnic minority individuals, with 78.8% of included patients identifying as White, and the low number of LRR events. As an unplanned secondary analysis of a clinical trial population, this study is underpowered for the primary end point of this analysis. As the trial was not designed with locoregional end points in mind, there are limited data points that do not allow for additional adjustment of factors that may be confounding, including genetic mutation status, margin status, or multifocal or multicentric disease. Further, radiation fields are not detailed, only the intent for radiation. Finally, there is inherent selection bias, as the outcomes of a clinical trial are not necessarily generalizable to the general population.
Conclusions
In this post hoc analysis of a randomized clinical trial, racial and ethnic differences in LRR were seen among patients with T1-2N0 HR-positive, ERBB2-negative breast cancer enrolled in TAILORx, with Asian and Black patients having the highest rates of LRR. Further study is needed to understand patterns of LRR in other breast cancer subtypes and whether failure to rescue after LRR contributes to disparities in BCM.
Trial Protocol
eTable 1. Cohort Characteristics and Treatment Receipt by Type of Surgery (N = 9396)
eTable 2. Cohort Characteristics and Treatment Receipt by Race and Ethnicity in Patients Undergoing Mastectomy (n = 2656)
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial Protocol
eTable 1. Cohort Characteristics and Treatment Receipt by Type of Surgery (N = 9396)
eTable 2. Cohort Characteristics and Treatment Receipt by Race and Ethnicity in Patients Undergoing Mastectomy (n = 2656)
Data Sharing Statement
