We demonstrated that AA patients enrolled onto cooperative group adjuvant breast cancer clinical trials had lower baseline WBC than white patients, but AA and white women had similar RDIs. AA women were more likely to experience early discontinuation of treatment and/or treatment delay, mostly because of an increase in missed appointments. The mean RDI was similar for both groups, with 43% of all women having an RDI of less than 85%. After adjusting for the components of chemotherapy treatment quality such as dose reductions and dose delays, BSA (or, alternatively, BMI), baseline WBC, and other known predictors of survival, AA women still had worse DFS and OS than white women.
We found that AA women with breast cancer had significantly lower baseline ANC and WBC counts than white women. This was similar to the results from other studies that found that WBC counts are 25% to 40% lower on average among AA patients than white patients.14,18
Racial differences in baseline WBC count may contribute to black patients' risk of receiving dose reductions or delays because low baseline WBC is one of the strongest predictors of an RDI of less than 85%. Again, however, despite the lower WBC and ANC counts in AA women, we did not find that AA women received lower total treatment doses compared with white women.
In our study and others, delays in treatment were common; however, we saw no association between race and dose delay, as noted earlier, or between dose delay and all-cause mortality (P
= .18 for DFS and P
= .23 for OS). Cumulative dose delays longer than 30 days have been found to increase the risk of relapse.7
In our sample, the delays may not have been long enough to affect survival; our study may have been underpowered to detect their effects; or under conditions that have resulted in delay in other studies, the patients in our sample may have been more likely to discontinue treatment entirely than to delay completing it. A better understanding of the barriers to complete and timely adjuvant treatment may lead to cost-effective interventions to target those at high risk for missed appointments and treatment delays and improve outcome for all women with breast cancer.
The relationship between race and dose-intensity in the treatment of breast cancer was assessed in a prior retrospective chart review study.11
AA patients received less chemotherapy than white patients (P
= .03), and overweight status (BMI > 25 mg/kg2
) seemed to modify the association of treatment with race. In a multivariable model, compared with normal- or low-weight white patients, normal- or low-weight AA patients were nearly four times as likely to receive lower dose treatment, and overweight AA patients were nearly 20 times as likely to receive lower dose treatment.11,19
Although we found that AA women had a higher baseline BSA (which is highly correlated with BMI), after adjusting for BSA, we did not find an association between race and RDI. However, higher BSA may contribute to recurrence risk by other mechanisms because studies have suggested that diet, exercise, and BMI may be associated with outcome in women with breast cancer.20,21
Despite the fact that the mean RDI of the cohort was 88%, 43% of all the women evaluated had an RDI of less than 85%. This is similar to a prior community-based study that found that only 45% of women received at least the threshold 85% RDI.9
The earliest adjuvant clinical trials showed that RDI was a predictor of survival, with patients receiving an RDI of less than 85% achieving substantially less benefit.22,23
Despite this, RDI is not routinely reported in clinical trials. Furthermore, randomized trials demonstrated that increasing the dose density of chemotherapy improved both DFS and OS.8,24
Few studies have evaluated the impact of RDI on survival with more modern chemotherapy regimens, and few trials report the percentage of patients who achieved more than 85% RDI; therefore, it is hard to know how these results compare with other clinical trials. A reassessment of this RDI cutoff may be warranted.
Despite controlling for treatment-related factors, known prognostic factors, and chemotherapy delivery, disparities in both DFS and OS were still observed. The reasons for this remain elusive. One possible explanation may involve differential rates of adherence to hormonal therapy because AA women may, on average, be less likely to complete a full 5-year course of adjuvant hormonal therapy and clinical trials do not usually measure hormonal therapy adherence.15
In addition, racial or ethnic differences in genes responsible for the metabolism of either chemotherapeutic agents or hormonal treatments may contribute to these findings, and this variability may affect both toxicity and effectiveness of the treatment.25,26
It is known that AA women with breast cancer, especially those who are premenopausal, seem to have a higher incidence of biologically more aggressive cancers that are basal-like or triple negative.27–29
This may be contributing to some of the disparity that we observed; however, one limitation to our study was the we were unable to look at this factor because of incomplete information on HER-2/neu
status. Survival differences by race were also observed for postmenopausal women and women with hormone receptor–positive tumors in our study, as well as others.2
Thus, our study refutes claims that the reason for racial disparities in adjuvant therapy outcomes is solely a result of frequency of triple-negative disease in the cohort analyzed.
Our study is unique in that patients were treated in a uniform fashion, detailed information on tumor characteristics was available, prospective evaluation of outcome was recorded, and the maximum follow-up time exceeded 15 years. Selection bias may limit the generalizability of the findings because patients who agree to participate in clinical trials are often more compliant and may be observed more closely than patients treated in the community and may be more adherent to tamoxifen therapy as well.
In summary, we have shown that AA women with breast cancer have lower WBC counts at baseline than white women. This did not result in a difference in RDI between the groups. However, AA women were more likely to experience early discontinuation or treatment delay, mostly as a result of missed appointments as opposed to toxicity or insufficient blood counts. Because we were unable to demonstrate that any factor related to treatment quality or delivery contributed to the racial difference in survival between the groups, further investigation into the etiology of this disparity is justified.