Pathologic complete response in breast cancer patients receiving anthracycline- and taxane-based neoadjuvant chemotherapy

Evaluating the effect of race/ethnicity

Authors


Abstract

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline- and taxane-based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence-free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor-positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49-0.97) and OS (HR, 0.63; 95% CI, 0.41-0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97-1.68] and OS: HR, 1.32 [95% CI, 0.97-1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.

Breast cancer is the second most common cause of cancer death among women in the United States. In 2009, more than 194,280 new cases were diagnosed and it is estimated that 40,610 deaths will occur.1 Despite the reduction in mortality rates across all ethnic groups over time, clear survival disparities exist between women of different racial groups. Reports obtained from the Surveillance, Epidemiology, and End Results (SEER) Program indicate higher age-adjusted mortality rates for black women compared with white women; this disparity is present among women aged > and <50 years.2 Several social, economic, and biological factors have been extensively studied to explain the observed racial disparities.3-6 Compared with whites, young black women have higher incidence of triple receptor-negative tumors, which could provide in part, the biological explanation of the poor prognosis noted in this group of patients.5, 7-9 To our knowledge, less information is available regarding Hispanics, but compared with whites, they appear to be more likely to have high-grade cancers, triple receptor-negative disease, larger tumors, and a greater number of positive lymph nodes at diagnosis.7, 10-12

Neoadjuvant systemic therapy (NST) is the standard approach to treat women with locally advanced and inflammatory breast cancer and is now being used in patients with earlier stage disease. By downstaging tumors; NST most likely improves available surgical options while concurrently allowing for in vivo assessment of chemosensitivity. Furthermore, attaining a pathologic complete response (pCR) after NST has been shown by several investigators to be a surrogate marker for improved long-term outcome, possibly due to the eradication of distant micrometastatic residual disease.13-19 A retrospective study from our institution demonstrated a survival benefit for patients who achieved a pCR compared with those who did not, regardless of hormone receptor status.20 Unfortunately, NST using conventional anthracyline- and/or taxane-based regimens results in pCR rates of only 8% to 31%.15, 17, 21, 22

The purpose of this study was to determine the associations between race/ethnicity, pCR, and survival outcomes after treatment with anthracycline- and taxane-based neoadjuvant chemotherapy. We also attempted to explore whether differences in pCR according to race were present among the different tumor subtypes. The interaction between race/ethnicity and pCR, according to recurrence-free survival (RFS) or overall survival (OS) was also evaluated.

MATERIALS AND METHODS

Patient Population

Patients treated with NST were identified in a prospectively maintained database in the Breast Medical Oncology Department at The University of Texas M. D. Anderson Cancer Center (UTMDACC). A total of 2074 female patients diagnosed with invasive primary breast cancer between 1994 and 2008 and treated with anthracycline- and taxane-based NST were included. We excluded female patients with metastatic disease at diagnosis and bilateral breast cancer and all male patients. The variables recorded included patient demographics (race, age, and menopausal status), tumor characteristics (histology; grade; lymphovascular invasion; and estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER-2] status), clinical stage at diagnosis (based on the criteria proposed by the American Joint Committee on Cancer Criteria version VI23), type of surgery, pathologic stage, and recurrence and survival information

Race information was self-reported based on data derived from forms completed by the patient on her first visit to our institution. The race/ethnicity groups evaluated were white, black, Hispanic, and other. All pathology specimens were reviewed by dedicated breast pathologists at UTMDACC. Histologic type and grade were defined according to the World Health Organization classification system24 and modified Black nuclear grade system,25 respectively. All surgical breast and axillary lymph node specimens were reviewed centrally by dedicated breast pathologists to identify the presence or absence of residual disease. pCR was defined as no residual invasive cancer in both the breast and the axillary lymph nodes.

Treatment

All patients were treated with a multidisciplinary approach, and they received NST with an anthracycline- and taxane-based regimen. Taxanes administered included paclitaxel at a dose of 175 to 250 mg/m2 intravenously (iv) on Day 1 every 21 days for 4 cycles, paclitaxel at a dose of 80 mg/m2 weekly for 12 doses, or docetaxel at a dose of 100 mg/m2 iv on Day 1 every 3 weeks for 4 cycles. Anthracycline regimens included 3 to 6 cycles of 1 of the following: 5-fluorouracil (5-FU) at a dose of 500 mg/m2, epirubicin at a dose of 100 mg/m2, and cyclophosphamide at a dose of 500 mg/m2 iv on Day 1 every 3 weeks; 5-FU at a dose of 500 mg/m2 on Days 1 and 4, epirubicin at a dose of 75 mg/m2, and cyclophosphamide at a dose of 500 mg/m2 iv on Day 1 every 3 weeks (FEC 75); 5-FU at a dose of 500 mg/m2 iv on Days 1 and 4, doxorubicin at a dose of 50 mg/m2 iv by continuous infusion over 72 hours, and cyclophosphamide at a dose of 500 mg/m2 on Day 1 every 3 weeks; or doxorubicin at a dose of 60 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 iv on Day 1 every 3 weeks. From the 468 patients with HER-2/neu-positive tumors, 55.6% (n = 260) received neoadjuvant trastuzumab at a dose of 4 mg/kg on Day 1 followed by 2 mg/kg weekly during 24 weeks. This regimen was given in combination with paclitaxel (225 mg/m2 every 3 weeks or 80 mg/m2 weekly) followed by FEC 75. To account for the effect of time in the selection of systemic therapy, we evaluated the distribution of the included patients according to their race/ethnicity by year of inclusion. After NST, all patients underwent definitive surgery. The decision for or against breast-conserving surgery was made based on recommendations made by the multidisciplinary team and patient preferences. The Institution Review Board of UTMDACC approved the study.

Statistical Analysis and Outcome Measures

We computed descriptive statistics. Patient characteristics were compared by pCR status and by race/ethnicity groups with a chi-square test or Wilcoxon rank sum test as appropriate. OS was calculated from the date of neoadjuvant chemotherapy response assessment (time of surgery) to the date of death or last follow-up. RFS was calculated from the date of neoadjuvant chemotherapy response assessment (time of surgery) to the date of first local or distant metastasis or last follow-up. Patients who died before experiencing a disease recurrence were considered censored at their date of death in the analysis of RFS.

Survival outcomes were estimated according to the Kaplan-Meier product limit method, and groups were compared with the log-rank test. Cox proportional hazards models were built to evaluate the association of pCR, race/ethnicity, and the interaction between the 2, with survival outcomes after adjustment for other patient and disease characteristics. All variables that were found to be significantly associated with race/ethnicity, pCR, and/or OS (P <.05) were considered for inclusion in the multivariable model. Test for interaction between race/ethnicity and pCR was evaluated in a model that included each of the survival outcomes. Age at diagnosis as a continuous variable, rather than menopausal status, was retained in the final model due to its clinical significance rather than statistical significance. Model selection was based on a backward selection procedure in which all variables of interest were included in a full model, and then variables were retained according to their 2-sided P values (P <.05).

We also considered the effect of race/ethnicity on pCR rates and survival outcomes within the 3 different breast cancer subtypes defined by receptor status: hormone receptor positive (ER or PR positive and HER-2 negative), HER-2 positive (regardless of hormone receptor status), and triple receptor negative (hormone receptor and HER-2 negative). The final model included breast cancer subtype, age at diagnosis, nuclear grade, lymphovascular invasion, and disease stage. P values <.05 were considered statistically significant; all tests were 2-sided. All analyses were performed using R 2.7.2 and SAS version 9.1 (SAS Institute, Inc, Cary, NC).

RESULTS

A total of 2074 patients were included; the median age was 50 years (range, 21-83 years). Three hundred two (14.6%) patients were black, 316 (15.2%) were Hispanic, 1334 (64.3%) were white, and 122 (5.9%) were of other race. Patients who were black or white tended to be postmenopausal and have older age at diagnosis (P <.0001), compared with those who were Hispanic or other race. Patients who were black tended to have higher clinical stage (P = .004) and higher nuclear grade (P = .0001), as well as triple receptor-negative disease more frequently (P = .003). Patient characteristics by race/ethnicity group are shown in Table 1.

Table 1. Patient and Tumor Characteristics According to Race/Ethnicity
 BlackHispanicWhiteOtherP
No. (N=302)%No. (N=316)%No. (N=1334)%No. (N=122)%
  1. HER-2 indicates human epidermal growth factor receptor 2; HR, hormone receptor.

Age at diagnosis, y         
Median50 47 51 47.5 <.0001
Menopausal status
 Premenopausal12441.0617254.4353440.037259.02 
 Perimenopausal or postmenopausal17557.9514144.6279459.525040.98<.0001
Histology         
 Ductal27089.4026786.13107880.8110787.70 
 Other3210.604313.8725619.191512.30.0006
Clinical stage
 I72.3292.85634.7210.82 
 II15350.6618859.4977458.027863.93 
 III14247.0211937.6649737.264335.25.004
Nuclear grade
 120.6672.22574.2743.28 
 27023.189630.3843332.463931.97 
 321872.1921066.4680360.197964.75.0001
Lymphovascular invasion
 Present7825.838526.9037027.742822.95 
 Absent19865.5622470.8991968.899073.77.706
Breast cancer subtype
 HER-2 positive5919.548025.3229722.263226.23 
 HR positive13043.0513943.9965949.406049.18 
 Triple receptor negative10133.447222.7829221.892520.49.003

Two hundred sixty patients (12.5%) achieved a pCR. Compared with patients who did not achieved a pCR, those who did tended to have higher nuclear grade disease (P <.0001), no lymphovascular invasion (P <.0001), and tumors that were HER-2 positive or triple receptor negative (P <.0001). There were no differences in pCR rates noted among racial/ethnic groups (12.3% in black, 14.2% in Hispanic, 12.3% in white, and 11.5% in other race patients; P = .788). When patients were stratified by tumor subtype, Hispanics appeared to have higher pCR rates compared with whites, but this difference did not achieve statistical significance. Race/ethnicity was not found to be significantly associated with obtaining a pCR within any of the receptor subgroups. pCR rates according to race and breast cancer subgroup are shown in Table 2.

Table 2. pCR and 5-Year Survival Estimates by Breast Cancer Subtype and Race/Ethnicity
pCRRFSOS
 Yes No. (%)No No. (%)PNo. of Events5-Year Estimate95% CIPNo. of Events5-Year Estimate95% CIP
  1. pCR indicates pathologic complete response; RFS, recurrence-free survival; OS, overall survival; 95% CI, 95% confidence interval; HER-2, human epidermal growth factor receptor 2; HR, hormone receptor.

All tumor subtypes
 All260 (12.5)1814 (87.5) 43870.8(68.3-73.5) 32775.7(73.1-78.4) 
 Black37 (12.3)265 (87.7) 9060.2(53.0-68.3) 7757.0(48.8-66.5) 
 Hispanic45 (14.2)271 (85.8) 5275.8(69.6-82.5) 3878.0(72.0-86.5) 
 White164 (12.3)1170 (87.7) 27671.7(68.6-74.9) 20178.9(75.1-81.2) 
 Other14 (11.5)108 (88.5).7882075.7(66.1-86.7)<.0011183.8(74.0-94.8)<.001
HER-2 positive
 All106 (22.6)362 (77.4) 9970.6%(65.3-76.4) 6479.9%(75.0-85.0) 
 Black14 (23.7)45 (76.3) 1760.0%(45.5-79.1) 1661.4%(44.8-84.0) 
 Hispanic20 (25.0)60 (75.0) 1374.9%(61.8-90.7) 884.8%(75.1-95.6) 
 White63 (21.2)234 (78.8) 6570.6%(64.3-77.7) 3880.7%(74.8-87.1) 
 Other9 (28.1)23 (71.9)0.756480.5%(64.5-100).157295.8%(88.2-100).001
HR positive
 All49 (5)939 (95.0) 14278.7%(75.3-82.2) 9583.90(80.5-87.5) 
 Black6 (4.6)124 (95.4) 2770.2%(60.0-82.1) 2364.0%(51.7-79.3) 
 Hispanic8 (5.8)131 (95.2) 1186.1%(78.4-94.6) 888.1%(78.8-98.5) 
 White35 (5.3)624 (94.7) 9778.6%(74.6-82.9) 5787.2%(83.6-91.0) 
 Other0 (0)60 (100)0.318782.6%(70.4-96.9).007774.0%(58.0-94.4)<0001
Triple receptor negative
 All95 (19.4)395 (80.6) 15259.8%(54.3-65.9) 13457.8%(51.8-64.4) 
 Black17 (16.8)84 (83.2) 3951.2%(38.7-67.8) 3351.2%(39.2-67.0) 
 Hispanic15 (20.8)57 (79.2) 1768.4%(55.1-85.1) 1370.5%(56.1-88.5) 
 White59 (20.2)233 (79.8) 8860.2%(53.4-68.0) 8654.8%(47.3-63.5) 
 Other4 (16.0)21 (84.0)0.843862.3%(44.3-87.6).151291.3%(80.5-100).029

The median follow-up was 30 months (range, 0-138 months). Among all patients, there were 438 recurrences (21.1%) and the RFS rate at 5 years was 70.8% (95% confidence interval [95% CI], 68.3-73.5%). Fifty-seven patients died before experiencing a recurrence (35 white patients, 9 Hispanic patients,12 black patients, and 1 patient of other race). Patients who achieved pCR had longer RFS compared with patients who did not (91.44% vs 67.88% at the end of 5 years; P <.0001). The 5-year unadjusted RFS estimates were 60.2% (95% CI, 53.0-68.3%) for blacks, 75.8% (95% CI, 69.6-82.5%) for Hispanics, 71.7% (95% CI, 68.6-74.9%) for whites, and 75.7% (95% CI, 66.1-86.7%) for other race, (P <.0001). pCR was associated with improved RFS regardless of race/ethnicity subgroup, and there was no evidence of an interaction between race/ethnicity and pCR. Figure 1 shows RFS by pCR groups for each of the race/ethnicity subgroups, and Table 2 shows RFS estimates. When examining RFS rates by race, according to breast cancer subtype, no difference was noted between patients with HER2-positive tumors or with triple receptor-negative tumors. However, among patients with hormone receptor-positive tumors the estimated percentage of patients alive and free of disease recurrence at 5 years was lower for black patients (70.2%; 95% CI, 60.0-82.1%) compared with Hispanic patients (86.1%; 95%CI, 78.4-94.6%), white patients (78.6%; 95% CI, 74.6-82.9%), and patients of other race (82.6%; 95% CI, 70.4-96.9%) (P = .007). In addition, among all patients, age >50 years (P = .009), peri/postmenopausal status (P = .019), hormone receptor-positive disease (P <.0001), early clinical stage (P <.0001), low tumor grade (P <.0001), and absence of lymphovascular invasion (P <.0001) were found to be associated with improved RFS.

Figure 1.

Recurrence-free survival (RFS) and overall survival (OS) by pathologic complete response (pCR) are shown according to race/ethnicity.

There were a total of 327 deaths and the OS rate at 5 years was 75.7% (95% CI, 73.1-78.4%). The results were similar to RFS, except that menopausal status and age at diagnosis did not retain statistical significance. Table 2 shows the 5-year OS estimates. Patients who achieved pCR had better survival compared with those who did not (93.6% versus 73.21% at 5 years; P <.0001). The unadjusted 5-year OS estimates were 57% (95% CI, 48.8-66.5%) for black patients, 78% (95% CI, 72.0-86.5%) for Hispanic patients, 79% (95% CI, 75.1-81.2%) for white patients, and 84% (95% CI, 74.0-94.8%) for patients of other race (P <.0001). Figure 1 shows OS curves by pCR for each of the race/ethnicity subgroups; inspection of the curves indicates no interaction between pCR and race/ethnicity. When examining OS by race according to breast cancer subtype, we observed that black patients had decreased crude rates of OS when compared with other races/ethnicities. Among patients with HER-2-positive tumors, 5-year OS rates were 61.4% (95% CI, 44.8-84.0%) in black patients, 84.8% (95% CI, 75.1-95.6%) in Hispanic patients, 80.7% (95% CI, 74.8-87.1%) in white patients, and 95.8% (95% CI, 88.2-100%) in patients of other race (P = .001). The 5-year OS rates for patients with hormone receptor-positive tumors were 64.0% (95% CI, 51.7-79.3%) for black patients, 88.1% (95% CI, 78.5-98.5%) in Hispanic patients, 87.2% (95% CI, 83.6-91.0%) in white patients, and 74.0% (95% CI, 58.0-94.4%) in patients of other race (P <.0001). Among women with triple receptor-negative breast cancer, the crude survival rates were 51.2% (95% CI, 39.2-67.0%) in black patients, 70.5% (95% CI, 56.1-88.5%) in Hispanic patients, 54.8% (95% CI, 47.3-63.5%) in white patients, and 91.3% (95% CI, 80.0-100%) in patients of other race (P = .029). In Figure 2, the RFS and OS rates by race for each triple receptor subgroups are shown.

Figure 2.

Recurrence-free survival (RFS) and overall survival (OS) are shown by tumor subtype and race/ethnicity. HER-2 indicates human epidermal growth factor receptor 2; HR, hormone receptor.

Table 3 shows the results of the multivariable models for RFS and OS. The final models include terms for race/ethnicity, pCR, breast cancer subtype, age at diagnosis, nuclear grade, lymphovascular invasion, and clinical stage. The interaction of pCR and race/ethnicity was not statistically significant for RFS (P = .53) or OS (P = .73), and therefore it was not included in the final models. After adjustments were made, patients who achieved a pCR were found to have a significantly decreased risk of both disease recurrence (hazard ratio [HR], 0.22; 95% CI, 0.13-0.36) and death (HR, 0.18; 95% CI, 0.10-0.34) compared to patients who did not achieve a pCR. Compared with white patients, Hispanic patients had a 31% reduction in the risk of disease recurrence (HR, 0.69; 95% CI, 0.49-0.97), and black patients had a 28% increase in the risk of disease recurrence, but this difference did not reach statistical significance (HR, 1.28; 95% CI, 0.97-1.68). For OS, compared with white patients, Hispanics had a 37% reduction in the risk of death (HR, 0.63; 95% CI, 0.41-0.97), and black patients had a trend toward an increase in the risk of death (HR, 1.32; 95% CI, 0.97-1.81). Patients of other races/ethnicities were not significantly different from white patients for both RFS and OS. To evaluate whether the observed differences in outcome were significantly affected by the small sample size, we built a multivariable model including the 1814 patients who did not achieve a pCR. Compared with white patients, Hispanics tended to have a reduction in the risk of disease recurrence (HR, 0.73; 95% CI, 0.52-1.04); black patients tended to have an increase in the risk of recurrence of the same magnitude as that observed for the cohort of patients who achieved a pCR (HR, 1.32; 95% CI, 1.00-1.75). For OS, using white patients as a reference category, similar estimates were noted, but they did not reach statistical significance (HR, 0.67 [95% CI, 0.43-1.57] and HR, 1.32 [95% CI, 0.95-1.82]).

Table 3. Multivariable Cox Proportional Hazards Models
 RFSOS
Hazard Ratio95% CIPHazard Ratio95% CIP
  1. RFS indicates recurrence-free survival; OS, overall survival; 95% CI, 95% confidence interval; pCR, pathologic complete response; HER-2, human epidermal growth factor receptor 2; HR, hormone receptor.

Age at diagnosis (continuous)0.99(0.99-1.00).31.01(0.99-1.02).29
Race      
 White1  1  
 Black1.28(0.97-1.68).0841.32(0.97-1.81).082
 Hispanic0.69(0.49-0.97).0340.63(0.41-0.97).035
 Other1.00(0.62-1.62).990.80(0.42-1.52).5
pCR      
 No1  1  
 Yes0.22(0.13-0.36)<.00010.18(0.10-0.34)<.0001
Breast cancer subtype
 HER-2 positive1  1  
 HR positive0.67(0.50-0.90).0070.83(0.58-1.20).33
 Triple receptor negative1.78(1.36-2.34)<.00012.82(2.02-3.95)<.0001
Clinical stage      
 I1  1  
 II1.45(0.68-3.10).3400.75(0.39-1.44).38
 III3.32(1.55-7.12).0021.97(1.01-3.80).045
Lymphovascular invasion      
 Absent1  1  
 Present1.85(1.48-2.30)<.00011.52(1.17-1.99).002
Nuclear grade      
 1 and 21  1  
 31.33(1.02-1.75).0371.79(1.26-2.54).001

No differences in the type of chemotherapy or proportion of patients receiving neoadjuvant trastuzumab according to race/ethnicity were observed. To account for the effect of time in the selection of systemic therapy, we evaluated the distribution of the included patients according to their race/ethnicity by year of inclusion. No difference in the race/ethnicity inclusion, according to 5-year cohorts, was observed.

DISCUSSION

The objective of the current study was to describe the effect of race/ethnicity and survival outcomes in patients with breast cancer treated with anthracycline- and taxane-based chemotherapy. In this large, single-institution study, we demonstrated that pCR rates are not related to race. We did not find a significant association between race/ethnicity and the likelihood of achieving a pCR. Furthermore, achieving a pCR was found to have a similar association with survival outcomes in each of the race/ethnicity subgroups. Consistent with other reports,20, 26 the results of the current study indicate that regardless of race, patients who achieved a pCR after anthracycline- and taxane-based NST had better RFS and OS compared with patients who did not achieve a pCR.

After adjustment for patient and disease characteristics, we found that Hispanic patients had significantly better RFS and OS compared with patients in other race/ethnicity groups. Black patients tended to have worse RFS and OS compared with patients in other race/ethnicity groups, but such differences did not achieve statistical significance. It is important to note that black patients tended to have disease characteristics associated with worse prognosis; of interest, the largest survival differences among blacks were observed in the hormone receptor-positive group. To the best of our knowledge, limited data are available with regard to outcomes in Hispanic patients. However, in a large population-based study that included 124,934 breast cancer patients, Li et al27 found that, after adjusting for stage, hormone receptor status, and surgical and radiation treatments, Hispanics had similar mortality rates compared with non-Hispanic whites (HR, 1.1; 95% CI, 0.8-1.3). Contrary results were found in black patients who tended to have worse outcomes (HR, 1.5; 95% CI, 1.4-1.6). Recent data from the SEER program2 indicate that, from 2002 through 2006, the age US adjusted overall mortality rates from breast cancer were lower for Hispanics (15.5/100,000) and higher for blacks (33.0/100,000) when compared with whites (23.9/100,000). Similar estimates were observed when examining only the 17 SEER areas. The improved health outcomes observed in Hispanic populations is a phenomenon described and referred to as the Hispanic paradox. This term specifically refers to the epidemiologic finding that Hispanics in the United States paradoxically tend to have substantially better health outcomes than the average population despite what their aggregate socioeconomic indicators would predict.28-31 The factors responsible for this observation are poorly understood. Even if underclassification of outcomes, migration, and acculturation play a role, it appears that unrecognized biological, environmental, cultural, and lifestyle factors could be important to understand these differences.30-33

Several studies have demonstrated that black women tend to present with more advanced stages at diagnosis and also have disease characteristics associated with worse outcomes, however, it is likely that the differences in outcomes that have been described are a result not only of differences in biology, but also differences in the patterns of care, socioeconomic and lifestyle factors, as well as access to health insurance and medical coverage.3-6, 8, 34, 35 Woodward et al36 explored the effect of race on survival in patients treated at UTMDACC on prospective clinical trials in which all patients received anthracycline-based chemotherapy. Despite uniform distribution of treatment, black patients were found to have poorer survival, with no differences found between Hispanics and whites. They suggested that maybe biologic differences play a major role to the poor survival observed among black patients with breast cancer. Contrary, Bradley et al,4 used data from the Detroit SEER program linked to Medicaid records to evaluate the association between race, breast cancer outcomes, and socioeconomic factors. They found that the association between race and outcomes lost statistical significance after controlling for Medicaid enrollment and poverty, suggesting that perhaps the differences reported are not solely to be explained by biology. When we examined the unadjusted 5-year RFS and 5-year OS rates, we observed interesting differences in outcome according to race, based on the tumor type; however, there results need to be interpreted carefully as baseline differences in known prognostic factors exist. Black patients with hormone receptor-positive disease had worse RFS and OS rates compared with whites, potentially reflecting differences in further access to healthcare or coverage for medications prescribed in the adjuvant setting (ie, tamoxifen or aromatase inhibitors) that may affect compliance. Although less clear, another possible contributing factor is a different percentage of black patients being poor CYP2D6 metabolizers.37, 38 Despite our short follow-up, similar results were very recently reported as part of a large randomized study. Sparano et al39 analyzed the effect of race and tumor subtype in outcome. They included participants of clinical trial E1199 (n = 4950). Patients were treated with adjuvant anthracycline- and taxane-based chemotherapy. With a median follow-up of 95 months, and after adjusting for potential confounders, the authors observed that black patients with hormone receptor-positive disease had worse disease-free survival and OS compared with whites (HR, 1.82 [95% CI, 1.36-2.44] and HR, 1.82 [95% CI, 1.18-2.78], respectively).

Dawood et al,26 in a database analysis from our institution, explored the effect of race in pCR among patients with triple receptor-negative tumors. Three-year RFS and 3-year OS rates were similar for the black group, compared with white/other race groups. After controlling for patient and tumor characteristics, race was not found to be significantly associated with RFS (HR, 1.08; 95% CI, 0.69-1.68) or OS (HR, 1.08; 95% CI, 0.69-1.68). Also, similar to our own results, no significant differences were observed when racial groups were divided according to pCR. We believe this is a very important observation, because it suggests that, among different races, pCR is an important surrogate marker of improved long-term outcome.

Contrary results have been reported by Balmanoukian et al.40 In a retrospective analysis of 38 patients with triple receptor-negative tumors who were treated with NST (33 of whom received anthracycline- and taxane-based NST), differences in outcome were observed according to race. With a median follow-up of 2.1 years, survival curves indicated shorter RFS and OS (P = .045 and .028, respectively) for African-American women compared with white/other women. This difference in results is likely related to small sample size, different patient populations, and differences baseline characteristics potentially not accounted for in the multivariable analysis. The report by Balmanoukian et al40 serves to highlight the fact that results of single-institution retrospective studies need confirmation from larger multi-institutional prospective studies.

To appreciate the findings of the current study, some strengths and limitations need to be addressed. To the best of our knowledge, this is the largest study evaluating the effect of race/ethnicity in pCR in patients treated with anthracycline- and taxane-based NST published to date. Despite the retrospective nature of our analysis, the database that we used was prospectively maintained. All the patients were treated at UTMDACC, allowing us to state with confidence that patients were treated with standard chemotherapy in a similar way, irrespective of their race, thereby reducing any potential bias derived from differences in treatment. Race was self-reported, and the only groups identified in our database were black, white, Hispanic, and other; therefore, it is possible that considerable heterogeneity exists within each group. It is possible that some differences in outcome did not achieve statistical significance when the analyses were made according to race and breast cancer subtype because of the small numbers of patients that achieved a pCR. In addition, this cohort of patients received homogeneous NST and surgical treatments, although differences in follow-up or compliance with subsequent therapy were not addressed. The median follow-up on our study was 30 months. This is potentially a limited follow-up time for the patients with hormone receptor-positive tumors. It is possible that, with longer follow-up, some differences become evident.

In conclusion, this study makes the important observation that, in this cohort of patients, race was not significantly associated with pCR rates in patients receiving anthracycline- and taxane-based NST. On multivariate analysis, we observed a trend toward worse outcomes in black patients, and also improved 5-year RFS and OS in Hispanics when compared with whites. Our observations need to be confirmed in a larger prospective study. Several questions remain unanswered regarding outcome differences among Hispanics and black patients, and further epidemiologic and molecular characterization of the tumors is needed to explore the potential differences in biology and outcomes.

CONFLICT OF INTEREST DISCLOSURES

Funded by National Institutes of Health K23 CA121994 and a Komen for the Cure Catalytic Award for Ana M. Gonzalez-Angulo.

Ancillary