Abstract
Context.
Limited research has examined racial disparities in symptom burden prior to chemotherapy initiation, during and at the chemotherapy completion.
Objective.
To describe and compare the symptom burden (fatigue, pain, and physical functioning) and change over time between Black and White women receiving Early-Stage Breast Cancer (ESBC) chemotherapy while considering social determinants of health.
Methods.
A longitudinal, repeated measures comparative design was employed. Time points of symptom measurement (PROMIS domains) at baseline, mid and end point were adjusted as per patient chemotherapy schedule. Linear mixed models were applied.
Results.
There were 149 patients, 36% Black 64% White (54 ± 12 years) recommended to receive ESBC chemotherapy with adequate data for symptom analysis.
Pain.
Main effect of race was significant (F(1, 390) = 29.43, P < .001) for pain.Black patients experienced significantly higher pain scores compared to White patients at pretherapy (Mean Difference; MD = 3.7, P = .034), midpoint (MD = 5.8, P = .002), and endpoint (MD = 7.8, P < .001). In the adjusted model, Black race and higher BMI were significant predictors of higher pain scores. Black patients experienced significant deterioration in pain over time.
Fatigue.
The scores for fatigue increased significantly from baseline for Black patients by endpoint (MDT1-T3 = 8.7, P < .001) and for White patients at midpoint (MDT1-T2 = 5.7) and at endpoint (MDT1-T3 = 10.1, P < .001). In the adjusted model, higher BMI predicted worse fatigue scores.
Physical function.
Black patients had significantly lower physical function scores compared to White patients at midpoint (MD = 4.0, P = .027). Physical function decreased by endpoint in Black (MDT1-T3 = 7.8, P < .001), and White patients (MDT1-T3 = 7.7, P < .001). In the adjusted model, only higher BMI and cardiopulmonary comorbidities significantly predicted worse physical function.
Conclusion.
Symptom burden significantly increased over the course of chemotherapy for all patients. Scores for pain and physical function were higher overall for Black patients and deteriorated at a greater rate for Black vs. White women over the course of chemotherapy. BMI was a significant predictor of pain, fatigue, and physical function, this assessment holds implications for proactive assessment and mitigation strategies.
Keywords: Racial disparities, breast cancer, symptom burden
Introduction
Breast cancer is the second leading cause of cancer-related deaths among women in the United States and the leading cause of cancer death among Black women.1,2 In recent years, the mortality rate from breast cancer has decreased due to increased emphasis on early detection and more effective treatments.3 Despite improvements in early detection,4 disparities in treatment and health outcomes remain, with Black American women experiencing the highest mortality rate related to breast cancer among all racial groups.3 Several factors are associated with breast cancer survival disparity, including later disease presentation4 and earlier age at diagnosis for Black women, a historic distrust of the health care system influencing screening and treatment decisions, and disproportionately poor communities that may offer few supports along the breast cancer care continuum.
Once cancer is diagnosed and treatment begins, disparities exist in the toxicities experienced during treatment. The 2002 State of the Science Conference for Cancer Symptom Management concluded that “all subjects with cancer should have optimal symptom control from diagnosis throughout the course of illness, regardless of personal and cultural characteristics.”5 Fifteen years later, this goal has not been achieved.6,7 To move forward in improving survival and health equity for Black women with breast cancer, further research is needed to deduce why Black women suffer disproportionately with symptom burden during chemotherapy.8
Racial Disparities in Symptoms Burden
Symptoms burden is defined as the “subjective, quantifiable prevalence, frequency, and severity of symptoms placing a physiologic burden on patients and producing multiple negative, physical, and emotional patient responses.”8 Historically, during early-stage breast cancer (ESBC), symptom burden increases from baseline to the midpoint of cancer treatment, at which point it remains stable until ESBC is terminated. Worsening symptom burden has been attributed to increasing gas-trointestinal symptoms, fatigue, insomnia, and concerns with appearance.9,10 Black women experience more severe symptoms during and post treatment for ESBC.11 Pain and fatigue are the most common distressing symptoms experienced by patients receiving treatment during ESBC treatment. The impact of these symptoms is poor quality of life, and overall diminution of physical function with implications for social, employment and family roles. It is imperative to examine the racial disparities in these symptoms prior to chemotherapy initiation, during and at the completion of chemotherapy.
Pain
Black women with ESBC report experiencing more severe pain than White women.12,13 This disparity is partly attributed to ongoing inequities in pain management, as Black patients are less likely to receive care aligned with clinical guidelines and are more likely to have their pain underestimated by healthcare providers.14 Additionally, higher pain intensity is associated with higher pain interference (i.e., the effect of pain on activities: cognitive, social, physical, and recreation), fatigue, sleep disturbances, depression, and anxiety.12,15
Fatigue
Compared to white women with breast cancer, Black women have higher levels of fatigue across domains (physical, emotional, etc.) shortly after diagnosis as well as during the early post-treatment survivorship phase (i.e., 6 to 18 months post-treatment).16 Racial comparisons of fatigue In breast cancer showed that for White patients, emotional fatigue and vigor increased from diagnosis to approximately 6 months post-treatment, whereas these symptoms remained stable among Black women with ESBC.16
Physical Function
Disparity in physical function has been reported between Black & White women during treatment and cancer survivorship.17,18 This disparity appears to be multifactorial. Black women were more than twice as likely to have a greater degree of physical functioning limitation compared to white breast cancer survivors, but this finding was significantly attenuated after adjusting for BMI, smoking status, and the presence of other co-morbid conditions associated with physical activity limitations.18 The mediating role of socioeconomic factors is important. Racial differences in physical and functional wellbeing are 50% weakened by socioeconomic differences. Physical function deficits can impact Black women’s ability to manage cancer and treatment-related symptoms such as physical activity and co-morbid conditions.17
The Importance of Considering Social Context
Social contextual determinants of health contribute to both the risk and outcomes of breast cancer and may also contribute to disparities in symptom burden. Social contextual factors include race and gender but also include socially patterned access to social, education, and economic resources, as well as exposure to other environmental hazards within communities. Life-time cumulative stress caused by the stressors of poverty and discrimination may accelerate aging and thus the symptom experience.19
In addition, psychosocial stress in early life has also been associated with elevated inflammation markers among women with breast cancer.20 Black women are more likely than White women to have lower socioeconomic status and are more likely to be exposed to psychosocial stressors in early childhood such as abuse and neglect.21 The cumulative impact of disparities in social contextual factors may increase the risk and adversely impact breast cancer outcomes through allostatic load or more rapid biological aging. The area deprivation index (ADI), a composite of neighborhood characteristics including poverty, housing, employment, and education, is associated with symptom burden, symptoms of depression and anxiety,22 including psychological well-being and quality-of-life23 in patients with cancer. Little research has looked at area deprivation within longitudinal data.
Previous work exploring racial differences in symptom burden during ESBC has focused primarily on pain,24 and retrospective assessments were often cross-sectional, or time points were not individualized for each patient treatment course of therapy.12,24 This methodology may not reflect a granular, over time assessment of symptoms during the treatment trajectory. Our study aims to advance our understanding of racial disparity in symptom burden during ESBC while considering the individual chemotherapy schedule and overcoming these methodological shortcomings.
Purpose
Limited studies have assessed racial disparities in pain, fatigue, and physical function prior to chemotherapy initiation and changes over the course of treatment, while adjusting for individual timing of chemotherapy for BC patients. The aims of this study are to describe and compare the symptom burden (fatigue, pain, and physical functioning) and change over time between Black and White women receiving ESBC chemotherapy while considering social determinants of health.
Methods
This study employed longitudinal, repeated measures (baseline, midpoint, and completion of chemotherapy) assessment time points were included in this analysis based on patient chemotherapy treatment plan; total time points range for all patients = 4–16), comparative, mixed-methods design. Women with ESBC in Western Pennsylvania and Northeast Ohio were followed over the course of chemotherapy. A convenience sample of patients who are: female, Black or White race, 18 years of age or older, and prescribed chemotherapy for a diagnosis of invasive breast cancer (stages 1–3) were included. Prior chemotherapy, metastatic breast cancer, impaired cognition, inability to understand English, and receiving treatment outside the clinic of consent were exclusion criteria. Further details regarding recruitment, enrollment, and data collection are reported by Nugent et al.25
Prior to COVID–19 research restrictions, eligible participants were approached by a research assistant in the clinic prior to receiving their first chemotherapy treatment. Following COVID-19 restrictions, the recruitment and consent were obtained by telephone and online. Informed consent was obtained, and baseline measures were completed by phone, online, or via paper forms. To capture the full range of changes in symptoms distress over the trajectory of ESBC chemotherapy, we included three time points: prior to chemotherapy (i.e., baseline), midpoint of treatment, and completion of chemotherapy (endpoint) for each patient. The data collection schedule was tailored to the individual patient’s chemotherapy schedule. For example, if a patient needed to have a 7-day treatment delay due to neutropenia, the data collection schedule was adjusted by 1 week.
Ethical approval was received from the Institutional Review Boards of (1) University of Pittsburgh (IRB number 19050299) and (2) University Hospitals Cleve-land Medical Center (IRB number 02-18-60C).
Measures
Area deprivation.
The area deprivation index (ADI) is a multidimensional evaluation of a neighborhood’s socioeconomic status.26 The Area Deprivation Index (ADI), developed by the Health Resources and Services Administration,26 allows for neighborhood rankings by socioeconomic status deprivation, a composite of several factors (income, education, employment, and housing quality). Scores range from 0 to 100, with higher scores indicating higher deprivation. National ADI was derived by entering participants’ home addresses at the time of study enrollment into a publicly available interactive website.27 Post office boxes are neither considered geographically representative nor included within American Community Survey metrics; thus, ADI was not calculated for participants who entered P.O. Boxes. The ADI median (61) was used to categorize participants into high ADI (n = 74; 50.7%), meaning living in areas of greater deprivation, and low ADI (n = 72; 49.3%), indicating living in areas of less deprivation.
Race.
Patient race was identified as either White or Black based on both self-reported demographic questionnaire and medical chart review.
Patient-Reported Outcomes Measurement Information System (PROMIS −29 Profile v 2.0)
The PROMIS-29 Profile (v2.0) was used to measure symptom burden.28 The PROMIS-29 is a 5-point Likert scale, including seven domains (anxiety, depression, fatigue, sleep disturbance, physical function, ability to participate in social roles and activities, and pain).
For this paper, symptom burden was defined through measurements of fatigue, pain, and physical function. Raw scores for all domains were converted into T-scores using the Health Measures System (mean of general US adult reference population = 50, SD = 10). Higher PROMIS T-scores represent more of the concept being measured (i.e., worse fatigue and pain and better physical function). The clinical thresh-old to evaluate within-group change or to make a between-group comparison generally ranges between 2 and 6 T-score points.29
Analytic Approach
Data were analyzed using IBM® SPSS®, version 27.30 Descriptive data (mean, standard deviation, frequency, and percentages) for raw data were provided. Pearson’s correlations (Spearman coefficients) were used to examine the bivariate associations of study variables. Linear mixed models were applied to determine whether significant differences existed in PROMIS domains over the three time points between Black and White patients. Next, linear mixed models adjusted for area deprivation, body mass index (BMI), and comorbidities (cardiopulmonary, and other cancer) were applied to examine whether symptom burden (pain, physical function, and fatigue) varied by race across the three time points.
Results
Participants
There were 149 patients, 36% Black, 64% White, with a mean age of 54 ± 12 years. Time average between prechemotherapy and midpoint (42 ± 16 days = 5.6 ± 2.3 weeks) and between midpoint and endpoint (71 ± 22days = 9.8 ± 3.2 weeks). Demographic and clinical characteristics of all participants and by race are presented in Table 1.
Table 1.
Descriptive and Comparative Statistics for Demographic Characteristics (N = 149)
| Variable | Total | Black N = 53(35.6%) | White N = 96(64.4%) | P-Value |
|---|---|---|---|---|
| Age (years)a | 54.01 ± 12.49(25-80) | 54.21 ± 11.84(25-73) | 53.90 ± 12.89(28-80) | .885 |
| Ethnicityb | .256 | |||
| Non-Hispanic | 146(98) | 51(96.2) | 95(99.0) | |
| Hispanic | 0(0.0) | 0(0.0) | 0(0.0) | |
| Unknown | 3(2.0) | 2(3.8) | 1(1.0) | |
| Marital statusb | <.001 | |||
| Partnered | 79(53.0) | 17(32.1) | 62(64.6) | |
| Nonpartnered | 70(47.0) | 36(67.9) | 34(35.4) | |
| Employment statusb (n = 148) | .425 | |||
| Employed | 89 (60.1) | 29(55.8) | 60(62.5) | |
| Nonemployed | 59(39.9) | 23(44.2) | 36(37.5) | |
| Educationb (n = 145) | .014 | |||
| High school or less | 45(31.0) | 22(44) | 23(24.2) | |
| College and more | 100(69.0) | 28(56.0) | 72.(75.8) | |
| ADIa | 59.8(27.2) | 77.8 ± 24.0(22-100) | 50.1 ± (8-100) | <.001 |
| BMIa | 31.5 ± 7.7(18-59) | 34.3 ± 6.8(18-52) | 29.9 ± 7.7(19-59) | <.001 |
| Comorbiditiesb | ||||
| Cardiopulmonary | <.001 | |||
| Yes | 41 (77.4%) | 38 (39.6%) | ||
| No | 12 (22.6%) | 58 (60.4%) | ||
| Other cancer | .033 | |||
| Yes | 1(7.7%) | 12 (12.5%) | ||
| No | 52(98.1%) | 84 (87.5%) | ||
| Insuranceb | .002 | |||
| No insurance | 3(2.0) | 2(3.8) | 1(1.0) | .164 |
| Public | 70(47.0) | 34(64.2) | 36(37.5) | |
| Private | 76(51.0) | 17(32.1) | 59(61.5) | |
| Religion background/preferenceb | .016 | |||
| Yes (Christian, Jewish, Muslim) | 114(76.5) | 44(83.0) | 70(72.9) | |
| No | 35(23.5) | 9(17.0) | 26(27.1) | |
| Importance of religion/spiritualityb (n = 114) | ||||
| Not important at all | 4(3.5) | 0 (0.0) | 4(5.7) | |
| Somewhat important | 34(29.8) | 8 (18.2) | 26(37.1) | |
| Extremely important | 76(66.7) | 36 (81.8) | 40(57.1) |
Note: Total N = 149 (unless specified).
ADI = area deprivation index.
Statistics for continuous type variables are reported as Mean ± SD(Min-Max).
Statistics for categorical variables are reported as n (%).
Primary Outcomes
Comparative statistics for primary outcomes and other study variables are presented in Table 2.
Table 2.
Comparative Statistics for Study Variables
| Total | Black |
White |
P-Value | |||
|---|---|---|---|---|---|---|
| Mean ± SD | Min-Max | Mean ± SD | Min-Max | |||
| PROMIS physical function | ||||||
| Time1 | 49.3 ± 8.9 | 47.9 ±10.3 | 26.9-56.9 | 50.2 ± 8.0 | 35.6-56.9 | .136 |
| Time 2 | 46.0(8.7) | 43.3 ± 9.4 | 26.9-56.9 | 47.4 ± 8.1 | 34.4-56.9 | .012 |
| Time 3 | 41.6(8.5) | 39.8 ± 9.2 | 22.9- 56.9 | 42.5 ± 8.0 | 22.9-56.9 | .093 |
| PROMIS pain | ||||||
| Time 1 | 49.8(10.1) | 52.1 ± 11.0 | 41.6-75.6 | 48.5 ± 9.4 | 41.6-66-6 | .035 |
| Time 2 | 49.2(9.3) | 53.0 ± 10.6 | 41.6-75.6 | 47.2± 7.9 | 41.6-66.6 | < .001 |
| Time 3 | 52.8(11.5) | 58.0 ± 12.2 | 41.6-75.6 | 50.2 ± 10.3 | 41.6-75.6 | < .001 |
| PROMIS fatigue | ||||||
| Time 1 | 48.3(10.1) | 49.2 ± 10.8 | 33.7-64.6 | 47.9 ± 9.7 | 33.7-69.0 | .459 |
| Time 2 | 53.8(10.2) | 54.1 ± 11.9 | 33.7-75.8 | 53.6 ± 9.2 | 33.7-71.6 | .793 |
| Time 2 | 58.0(9.6) | 58.1 ± 11.1 | 33.7-75.8 | 57.9 ± 8.7 | 33.7-75.8 | .938 |
Note: PROMIS = patient-reported outcomes measurement information system.
Pain.
Black patients, compared to White patients, experienced significantly higher pain scores F (1,390) = 29.429, P < .001) across all time points, with a mean difference (MD) of 3.7 (P = .034) prior to chemotherapy initiation (baseline), 5.8 (P = .002) at midpoint, and increased to 7.8(P < .001) by completion of chemotherapy. After adjusting for area deprivation, BMI, and comorbidities, the main effect of race was still significant (F (1,379) = 8.480, P = .004) for pain with Black patients experiencing significantly higher pain scores compared to White patients at the completion of chemotherapy (mean difference; 6,023, P = .02).
Pain scores deteriorated significantly over time for Black patients (within group change) who reported a significant increase in pain scores by the completion of chemotherapy (MDT1-T3 = 5.8, P = .015). These disparities remain significant after adjusting for covariates; Black patients reported a significant increase in pain scores by the completion of chemotherapy (MDT1-T3 = 6.058, P = .008; MDT2-T3 = 5.711, P = .021). There were no significant changes in pain scores over time among White patients. Refer to Table 3 for marginal means contrasts for mixed models depicting within-group changes and Table 4 for marginal means contrasts between Black and White at the three time points. Higher BMI was associated with greater pain interference (F(1,379) = 21.071, P < .001).
Table 3.
The Marginal Means Contrasts for Each Combination of Within-Subject Variable
| Contrast | Unadjusted Model |
Adjusted Model |
||||
|---|---|---|---|---|---|---|
| Mean Difference | SE | Significance | Mean Difference | SE | Significance | |
| Pain | ||||||
| Black | ||||||
| T1-T2 | −0.868 | 2.058 | 1.000 | −0.347 | 2.025 | 1.000 |
| T1-T3 | −5.810* | 2.058 | .015 | −6.058* | 2.009 | .008 |
| T2-T3 | −4.942 | 2.154 | .067 | −5.711* | 2.110 | .021 |
| White | ||||||
| T1-T2 | 1.239 | 1.510 | 1.000 | 1.162 | 1.456 | 1.000 |
| T1-T3 | −1.711 | 1.505 | .769 | −1.795 | 1.456 | .654 |
| T2-T3 | −2.950 | 1.564 | .180 | −2.958 | 1.509 | .152 |
| Physical function | ||||||
| Black | ||||||
| T1-T2 | 4.605* | 1.775 | .030 | 4.094 | 1.740 | .057 |
| T1-T3 | 8.044* | 1.775 | < .001 | 7.668* | 1.727 | < .001 |
| T2-T3 | 3.440 | 1.865 | .198 | 3.574 | 1.822 | .152 |
| White | ||||||
| T1-T2 | 2.774 | 1.308 | .104 | 2.759 | 1.257 | .086 |
| T1-T3 | 7.636* | 1.304 | < .001 | 7.713* | 1.257 | < .001 |
| T2-T3 | 4.862* | 1.355 | .001 | 4.954* | 1.303 | < .001 |
| Fatigue | ||||||
| Black | ||||||
| T1-T2 | −4.916 | 2.057 | .052 | −4.924 | 2.097 | .058 |
| T1-T3 | −8.897* | 2.057 | < .001 | −8.658* | 2.107 | < .001 |
| T2-T3 | −3.981 | 2.15 | .195 | −3.734 | 2.186 | .260 |
| White | ||||||
| T1-T2 | −5.706* | 1.509 | < .001 | −5.605* | 1.508 | < .001 |
| T1-T3 | −10.050* | 1.504 | < .001 | 10.117* | 1.508 | < .001 |
| T2-T3 | −4.344* | 1.563 | .017 | −4.512* | 1.563 | .012 |
Notes. T1 = prechemotherapy; T2 = midpoint; T3 = endpoint.
Raw model included race, time, and race time interaction. Adjusted models included area deprivation, body mass index, comorbidities, time, and race time interaction.
Adjustment for multiple comparisons: Bonferroni.
The mean difference is significant at the .05 level.
Table 4.
The Marginal Means Contrasts for the Mixed Models Between Black and White
| Contrast Black-White | Unadjusted Model |
Adjusted Model |
||||
|---|---|---|---|---|---|---|
| Mean Difference | SE | Significance | Mean Difference | SE | Significance | |
| Pain | ||||||
| Prechemotherapy | 3.665 | 1.723 | .034 | 1.761 | 1.822 | .334 |
| Midpoint | 5.772* | 1.884 | .002 | 3.270 | 2.005 | .104 |
| Endpoint | 7.764* | 1.880 | < .001 | 6.023* | 1.958 | .002 |
| Physical function | ||||||
| Prechemotherapy | −2.284 | 1.483 | .124 | −0.592 | 1.563 | .705 |
| Midpoint | −4.115* | 1.632 | .012 | −1.927 | 1.731 | .266 |
| Endpoint | −2.692 | 1.629 | .099 | −0.547 | 1.691 | .746 |
| Fatigue | ||||||
| Prechemotherapy | 1.679 | 1.854 | .366 | 0.874 | 1.887 | .644 |
| Midpoint | 0.947 | 2.052 | .645 | 0.194 | 2.077 | .926 |
| Endpoint | 0.358 | 1.998 | .858 | −0.585 | 2.028 | .773 |
Notes. The unadjusted model included race, time, and race time interaction. Adjusted models included area deprivation, body mass index, comorbidities, time, race, and race time interaction.
Adjustment for multiple comparisons: Bonferroni.
The mean difference is significant at the .05 level.
Fatigue.
Time was significant for fatigue in the unadjusted and adjusted models. Among Black patients, fatigue scores significantly increased (deteriorated) by endpoint (MDT1-T3 = 9, P < .001). Among White patients, fatigue scores significantly deteriorated by midpoint (MDT1-T2 = 6, P < .001) and at endpoint (MDT1-T3 = 10, P < .001). The main effect of race for fatigue was nonsignificant (P > .05) in both models. BMI was identified as a significant predictor of fatigue (F (1,379) = 7.230, P = .007); with each one-unit increase in BMI, fatigue scores increased by 0.203 points.
Physical function.
Main effect of race was significant (F(1, 391) = 10.998, P < .001) for physical function in the unadjusted model. Black patients had significantly lower physical function scores compared to White patients at midpoint (MD = 4.1, P = .012). The main effect of time was significant; physical function decreased among Black patients by endpoint (MDT1-T3 = 8.0, P < .001) and in White patients by endpoint (MDT1-T3 = 7.7, P < .001; MDT2-T3 = 4.9, P = .001). In the adjusted model, time, BMI, and cardiopulmonary comorbidities were significant predictors of physical function, and the main effect of race was reduced. Higher BMI (F(1,380) = 14.255, P < .001) was significantly associated with lower physical functioning scores. Patients with cardiopulmonary comorbidities had scores that were 3.05 points lower than those without these conditions (F(1,380) = 9/192, P = .003).
Associations of Area Deprivation and Study Variables
Of all correlations examined between ADI and outcomes at the three time points, living in areas of greater deprivation was associated with greater pain interference (r = −.227, P = .002, 56.3 vs. 50.1) and worse physical function (r = −.190, P = −.035, 40.6 vs. 42.4) at the completion of chemotherapy.
Discussion
This paper compared symptom burden (fatigue, pain, and physical function) and the changes experienced throughout chemotherapy between Black and White women with ESBC. The importance of this study lies in its novelty of examining these commonly reported symptoms at a time point often overlooked in the literature,prior to chemotherapy initiation. Furthermore, tracking changes at time points that reflect the full symptom trajectory including mid and endpoint of chemotherapy for each patient while considering the influence of area deprivation.
Notable Racial Disparities in Pain Present at Pretherapy and Escalate Over the Course of Chemotherapy (Unadjusted Model)
Prior to chemotherapy initiation, Black patients reported pain scores 4 points greater than White patients, indicating a clinically significant difference. This could be associated with the distress occurring while anticipating treatment,31 psychological and physical symptoms, area deprivation, and worsened economic hardships.32 This disparity continued to escalate over the course of chemotherapy, with Black patients reporting 6 points greater at midpoints and 8 points greater toward the completion of chemotherapy. This aligns with a cross-sectional study of 40 women with ESBC, status postinitial radiation or chemotherapy for breast cancer, where Black patients (58%) had significantly higher pain scores12 and another study where Black patients reported more pain-related interference with function than White patients.33 Our study contributes to the existing knowledge of racial disparities in a period that is overlooked in the literature,after diagnosis and prior to chemotherapy initiation.; These findings showed that the exacerbation of pain was greater among Black women over the course of chemotherapy. While the etiology of the pain is not fully examined in this analysis, the racial differences, and then exacerbation are important to note.
Within-group changes emphasized disparity as a clinically notable deterioration in pain scores over the course of chemotherapy was evident for Black patients only. The continuous deterioration in pain scores for Black patients across chemotherapy aligns with a recent study by Hu et al. where Black women with ESBC, followed from the initiation of chemotherapy to one year later, were more likely to experience significant increases in physical and psychological symptom burden during chemotherapy. This greater symptom burden was associated with less adherence to adjuvant endocrine therapy suggesting that better symptom management for Black women can reduce racial disparities in adherence and cancer outcomes.34 Our findings, along with previous research on racial disparities, provide evidence that Black patients endorse higher rates of pain.35 However, evidence has shown that Black patients receive inadequate and biased pain assessments and treatment by clinicians.36 Measures ensuring that clinicians and other healthcare providers deliver appropriate assessment and pain assessment to all patients should be taken.
Adjusting for BMI and Area Deprivation Eliminated Racial Disparity in Pain Experienced Prior to Chemotherapy Initiation
BMI is a significant predictor of pain, indicating that higher BMI is associated with greater pain interference. This is consistent with a longitudinal study of ESBC survivors (N = 1183), where overweight and obesity were identified as significant risk factors for long-term pain.37 Even after adjusting for BMI and area deprivation, race remained a significant predictor of pain. This aligns with racial disparities in other cancer outcomes in which both obese and nonobese Black women with ESBC (stages 0-II) had significantly higher hazards of progression compared to non-Black, obese women.38 Of note, every one-unit increase in BMI was associated with 0.334 point increase in pain interference scores. This indicates that a substantially higher BMI could lead to clinically significant changes in pain. Although BMI alone does not fully explain the pain in Black patients, interventions targeting BMI are warranted considering that Black patients are twice as likely as White patients to have a BMI ≥30 kg/m2, which may complicate breast cancer outcomes.39
Area deprivation broadly refers to the lack of economic and social resources in a neighborhood.40 After we adjusted for area deprivation in the models, the racial differences in pain at baseline were not statistically significant. In addition, patients residing in areas of greater deprivation from this sample reported higher pain and worse physical function by the completion of chemotherapy. This is consistent with previous studies where patients with advanced cancer who lived in areas of greater deprivation reported worse symptom burden and worse symptoms of depression and anxiety.22 Clinicians need to consider neighborhood deprivation when examining racial disparity. The ADI can be utilized in the healthcare system as an objective and publicly available measure of social context. High ADI scores can prompt healthcare providers to conduct further assessments of the patient’s socioeconomic needs and provide the appropriate referral and support within the community. This could mitigate the influence of neighborhood deprivation on racial disparities in symptom burden.
Fatigue Scores Significantly Worsened for Both Black and White Patients by the End of Chemotherapy
Both Black and White patients experienced an increase in fatigue scores over time (9 and 10 points, respectively), indicating clinically significant deterioration by the end of chemotherapy.
While BMI was identified as a statistically significant predictor of fatigue in this sample, it did not reach clinical significance, meaning that only a substantially high BMI could increase fatigue. Fatigue during the cancer experience, and specifically throughout chemotherapy, is well documented. The etiology is believed to be multifactorial, involving factors such as the disease process, treatment, and other symptoms, including pain.41 Our findings along with previous studies emphasize that fatigue is a common side effect of chemotherapy in breast cancer survivors regardless of race.12
Racial Disparities Were Noted for Physical Function at Midpoint and Were Eliminated After Adjusting for BMI and Cardiopulmonary Comorbidities
Both Black and White patients experienced deterioration in physical function by the end of chemotherapy in both unadjusted and adjusted models. In the unadjusted model, race was a significant predictor of physical function with Black patients experiencing greater deterioration in physical function compared to White patients at midpoint. However, after adjusting for covariates, BMI and cardiopulmonary comorbidities emerged as significant predictors of physical functioning, and racial disparity was eliminated. Our findings align with a previous study of breast cancer survivors, in which Black survivors experienced significantly higher limitations in physical function than White survivors in the unadjusted model.18 However, these disparities were eliminated after adjusting for BMI and comorbidities. Of note, each one-unit increase in BMI reduced physical functioning scores by 0.237, whereas the presence of cardiopulmonary comorbidities decreased physical function by 3.05 points. These findings collectively emphasize the critical role of modifiable factors such as BMI and comorbidities in explaining racial disparities in physical function among breast cancer survivors.
While there are many interventions to target poor physical function, such as support and physical activity groups, exercise, nutrition, and mindfulness programs, the effectiveness of these for Black patients during treatment is not identified.42,43 Culturally tailored interventions have shown improvement in other areas of breast cancer such as improving screening rates among African Americans and other minorities.44 Culturally tailored symptom assessment and management needs to be a top priority to ensure personalized cancer care for not just treatment, but in symptom assessment and management as well.
Strengths and Limitations
To our knowledge, our study is the first to look at the racial differences in the most common reported symptoms of pain, fatigue and physical function while accounting for the influence of area deprivation and considering patient-individualized timing of chemotherapy initiation, midpoint, and completion. This study addressed the methodological limitations identified in previous research, including the utilization of longitudinal data with a focus on time points that reflect the complete picture of changes in symptoms while receiving chemotherapy, including substantially larger sample size and accounting for area deprivation, which is considered a valid measure reflecting patient social status and associated with health-related outcomes. However, these findings should be interpreted with caution, considering any distress or anxiety that triggered by the COVID-19 pandemic,45 which might have influenced the symptoms burden.
Clinical Implications and Future Research
The baseline symptoms that patients bring to BC prior to chemotherapy initiation and the rate at which symptoms deteriorate must inform medical oncology practice. Practitioners and clinicians should consider symptom burden prior to chemotherapy initiation to accurately identify patients with prior symptoms that could be related to other comorbidities or the stage of diagnosis and avoid mistakenly attributing these symptoms as chemotherapy-related toxic effects.
Symptom management strategies need to be tailored and patient-centered, incorporating the differences that race and area deprivation may bring to the symptom experience during breast cancer chemotherapy. Frequent reports of clinicians not recognizing the severity of symptoms underline the need for a change systemically. Identification of patients with high symptom burden at baseline should prompt a protocol of support during chemotherapy.46
Black patients have the greatest unmet needs related to symptom burden but are also less likely to be assertive and communicate concerns efficiently with their physicians.47,48 While this may primarily be a problem of cultural barriers in a nonconcordant patient-physician relationship,49 a standardized measurement of symptom assessment and management is essential to attenuate the likelihood of chemotherapy dose reduction or early treatment cessation for Black patients.
Understanding symptom burden within the context of race prior to and during chemotherapy could provide a better understanding of the influence of racial disparities on the breast cancer chemotherapy experience. Establishing these symptom differences can help to provide the impetus to proactive, targeted symptom management.
Ethics Approval and Consent to Participate
This study was approved by the Institutional Review Boards of the University of Pittsburgh (IRB number 19050299), the University Hospitals Medical Center/Case Western Reserve University (IRB number 02-18-60C), and Allegheny Health Network (IRB number 2018-115), prior to commencement of human subject research. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.
Key Message.
This longitudinal study compared symptom burden (fatigue, pain, and physical function) and the changes experienced throughout chemotherapy between Black and White women with early-stage breast cancer. Symptom burden significantly increased over the course of chemotherapy for all patients. Racial disparities were noted in pain and physical function, with Black patients having worse levels and experiencing deterioration at a greater rate compared to White patients. Higher body mass index predicted worsened symptom burden.
Disclosures and Acknowledgments
This work was supported by the National Institute on Minority Health and Health Disparities [R01MD012245, Rosenzweig, PI]. Dr. Brufsky is a consultant for: Astra-zeneca, Pfizer, Novartis, Lilly, Genentech/Roche, SeaGen, Daiichi Sankyo, Merck, Agendia, Sanofi, Puma, Myriad, Gilead. Research Support: Agendia, Astrazeneca. The other authors declare no conflicts of interest. We would like to thank the participants for their time.
Footnotes
Consent to Participate
Informed consent was obtained from all individual participants included in the study.
Availability of Data and Materials
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Contributor Information
Hiba Abujaradeh, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.
Julia O’Brien, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.
Susan R. Mazanec, Case Western University Frances Payne Bolton School of Nursing, Cleveland, OH, USA.
Catherine M. Bender, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.
Isabelle M. Schlemmer, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA
Adam M. Brufsky, University of Pittsburgh Medical Center UPMC Hillman Cancer, Pittsburgh, PA, USA.
Elham Nasrollahi, UPMC Pinnacle, Harrisnurgh, PA, USA.
Margaret Rosenzweig, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.
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