Racial Disparities Magnified in Cardiac Dose, Toxicity Differences With RT for Breast Cancer

Reshma Jagsi, MD, DPhil

Racial and ethnic disparities for mortality and morbidity are present in breast cancer, especially as it relates to radiation therapy toxicity, cardiac dose, hypofractionation, and more. However, Reshma Jagsi, MD, DPhil, said a presentation during the 2024 Miami Breast Cancer Conference that oncology practices can remediate the inequities at the clinical setting.¹

According to Jagsi, a Lawrence W. Davis professor and chair in the Department of Radiation Oncology at Emory University School of Medicine, Winship Cancer Institute, in Atlanta, Georgia, these disparities have been observed across multiple human health conditions, including breast cancer. From a radiation oncologist perspective, she discussed the data in detail to help better understand and target the causal mechanisms behind said disparities.

Jagsi highlighted differences in mortality, morbidity, and financial toxicity for Black women in the United States.

“In fact, Black women have a death rate from breast cancer in the United States that is 40% higher than that of White women,” Jagsi said. “That is absolutely unacceptable.”

Additionally, Black women appear to have a lower likelihood of receiving more efficient and less toxic hypofractionated radiotherapy regimens and are more likely to have pain during treatment. Treatment-related adverse effects (TRAEs) are more likely to be underrecognized in Black women by their providers, Jagsi said, adding that these patients tend to receive higher cardiac doses.

“Understanding the underlying mechanisms by which these unacceptable disparities develop can suggest fruitful paths for interventions to ensure that the benefits of the many advances we have made in treating breast cancer reach all patients equitably,” Jagsi added.

Disparities in Screening, Financial Toxicity, and Hypofractionation

Causal mechanisms of racial and ethnic disparities may be rooted in various stages of a patient’s treatment course, including screening, surgery, systemic therapy, and radiotherapy, Jagsi highlighted.

Black women are less likely to get their mammograms done and have longer delays to follow-ups for an abnormal result. Data published in Annals of Internal Medicine found that initiating biennial screening in Black women who are 40 years old may reduce breast cancer mortality disparities, thereby producing benefit/harm ratios comparable with tradeoffs observed in White women who receive biennial screening who are 50 to 74 years.²

Long-term financial burden among different patient demographics with breast cancer has been another area of interest. Debt for treatment appeared significantly variable according to race among 1502 patients who responded to 2 surveys. Overall, 9% of White patients reported experiencing debt following medical treatment compared with 15% of Black patients, 17% of English-speaking Latina patients, and 10% of Spanish-speaking Latina patients.³

Specifically, Jagsi said that certain patients, including those who were self-employed, do not have flexible working hours, and need to pay for parking and transportation, have “meaningful costs” while receiving radiotherapy. As part of addressing some of these financial toxicities, she highlighted evidence-based guidelines from the American Society for Radiation Oncology (ASTRO) reporting that it was safe and effective to treat patients with 3 weeks of hypofractionated radiation rather than a standard course of 5 weeks.⁴

However, findings from a study published in International Journal of Radiation Oncology highlighted inequal use of hypofractionated whole breast radiotherapy for patients based on racial and ethnic backgrounds.⁵ In 2018, it was reported that 72.7% of White patients received hypofractionated radiation compared with 56.7% of Black patients and 67.6% of Asian patients (P = .04). In a multivariate analysis accounting for factors such as treatment year, age, body mass index, breast volume, comorbidities, and guideline eligibility, being Black or Asian significantly correlated with a reduced probability of receiving hypofractionated whole breast radiation treatment (P <.001). Multilevel modeling, however, appeared to eliminate this disparity, which suggested that differences in facility-specific use of hypofractionated radiation may have contributed to this imbalance.

“There’s something going on [but] not at the individual level; it’s not that one provider is deciding to treat a Black patient differently from a White patient,” Jagsi said concerning these data. “The practices that were more likely to have Black patients were less likely to use hypofractionation.”

Disparities in Toxicity

The presentation also focused on disparities related to toxicities associated with radiotherapy and physicians underreporting toxicity among racial and ethnic minority populations.

In a study that Jagsi authored and published in the Journal of Clinical Oncology, she and coinvestigators assessed patient-reported outcomes (PROs) among a large, multicenter cohort of patients who received radiotherapy for breast cancer.⁶ Of note, the rates of moderate or severe breast pain among those who received hypofractionated radiation was 26.1% for White patients, 43.0% for Black patients, 26.3% in Asian patients, and 44.0% for patients of other races. Among patients who received conventionally fractionated treatment, the toxicity rates in each respective group were 41.1%, 62.5%, 46.3%, and 61.6%.

In another report that Jagsi et al published in JAMA Oncology, the incidence of toxicity associated with breast radiotherapy was compared based on reports from 9941 patients and their physicians.⁷ Underrecognition of symptoms were highlighted in 30.9% (n = 2094/6781) of patient reports of moderate or severe pain, 36.7% (n = 748/2039) of reports of frequent pruritus, 51.4% (n = 2309/4492) of reports of frequent edema, and 18.8% (n = 390/2079) of reports of substantial fatigue. Among patients who reported 1 or more substantial symptoms, physicians underrecognized at least 1 symptom at least once for 53.2% (n = 2933/5510). Additionally, Black patients were more likely to have their symptoms underrecognized compared with White patients (odds ratio [OR], 1.56; 95% CI, 1.30-1.88; P <.001), as were patients of other races or ethnicities compared with White patients (OR, 1.52; 95% CI, 1.12-2.07; P = .01).

According to Jagsi, a higher proportion of larger patients tend to experience skin toxicities associated with radiation. Additionally, she said that Black women may be less likely to have access to the types of food that lead to smaller body sizes due to social policies that stem from institutional or structural racism. Due to the physical properties of photon beams, which must stretch further apart across thicker tissue, Jagsi hypothesized that there may be more variability in the dose distribution of radiation for larger patients, thereby contributing to the aforementioned toxicity observed in Black women.

Cardiac Dose Disparities

Jagsi highlighted findings from a study published in Journal of The National Cancer Institute to demonstrate racial and ethnic disparities with respect to cardiac doses in radiotherapy for breast cancer.⁸

According to the study investigators, being Black or Asian independently correlated with higher mean heart doses for most laterality-fractionated radiation groups, as there were disparities of up to 0.42 Gy for Black patients and 0.32 Gy for Asian patients. Additionally, these dose disparities translated to an estimated 2.6 more cardiac events and 1.3 more deaths per 1000 Black patients as well 0.7 more cardiac events and 0.3 more deaths per 1000 Asian patients compared with White patients.

Jagsi partly attributed these disparities to a structural factor known as “deep inspiration breath hold” (DIBH) use. When controlling for the method of radiation, which included DIBH, the dose disparity for Black patients decreased by 30%. In the study, DIBH was implemented for 14% of Black patients compared with 30% to 45% of Asian and White patients who received conventional fractionation for left-sided disease.

Facility availability may have influenced the use of DIBH, Jagsi hypothesized. Providers did not use DINH during the study period at the 2 facilities in which 50% of Black patients received treatment. She said that this discrepancy may illustrate how structural racism can impact facility-level disparities, as DIBH is reportedly affordable for most departments but can become less accessible due to inequities in payor mix across facilities.

“My colleague, Shearwood McClelland III, MD, is leading an interesting navigator-assisted hypofractionated program that is intended to increase the use of less toxic, less burdensome, and less costly form of hypofractionated care that is now standard and available,” Jagsi said concerning a potential strategy for targeted interventions for Black patients with breast cancer.⁹

Future Clinical Practice

Jagsi summarized the key implications of the findings she presented by stating that these racial and ethnic disparities in care were not just inequalities but inequities that violate what she described as a Kantian categorical moral imperative.

“We all have human dignity that merits respect for its own sake because we have the ability for rational thought and freely willed action,” she elaborated.

“In order to respect human dignity, we cannot allow these disparities to persist. I truly believe that most of us are good people—we’re trying to live our lives, help our patients, and contribute to society. We all have opportunities to make conscious choices about whether to perpetuate or remedy these ongoing wrongs. We cannot ignore this. I do believe the vast majority of us are going to do the right thing if we reflect on the evidence.”

References

1. Jagsi R. Understanding and mitigating disparities: a radiation oncologist’s perspective. Presented at the 41st Annual Miami Breast Cancer Conference. March 7-10, 2024; Miami, FL.
2. Chapman CH, Schechter CB, Cadham CJ, et al. Identifying equitable screening mammography strategies for black women in the United States using simulation modeling. Ann Intern Med.2021;174(12):1637-1646. doi: 10.7326/M20-6506
3. Jagsi R, Pottow JA, Griffith KA, et al. Long-term financial burden of breast cancer: experiences of a diverse cohort of survivors identified through population-based registries. J Clin Oncol.2014;32(12):1269-1276. doi:10.1200/JCO.2013.53.0956
4. Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol.2018;8(3):145-152. doi:10.1016/j.prro.2018.01.012
5. Laucis AM, Jagsi R, Griffith KA, et al. The role of facility variation on racial disparities in use of hypofractionated whole breast radiation therapy. Int J Radiat Oncol Biol Phys. 2020;107(5):949-958. doi:10.1016/j.ijrobp.2020.04.035
6. Jagsi R, Griffith KA, Vicini F, et al. Toward improving patients' experiences of acute toxicity from breast radiotherapy: insights from the analysis of patient-reported outcomes in a large multicenter cohort. J Clin Oncol. 2020;38(34):4019-4029. doi: 10.1200/JCO.20.01703
7. Jagsi R, Griffith KA. Vicini F, et al. Identifying patients whose symptoms are underrecognized during treatment with breast radiotherapy. JAMA Oncol. 2022;8(6):887-894.doi: 10.1001/jamaoncol.2022.0114.
8. Chapman CH, Jagsi R, Griffith KA, et al. Mediators of racial disparities in heart dose among whole breast radiotherapy patients. J Natl Cancer Inst. 2022;114(12):1646-1655. doi:10.1093/jnci/djac120.
9. McClelland III S, Harris EE, Spratt DE, et al. Navigator-assisted hypofractionation (NAVAH) to address radiation therapy access disparities facing African-Americans with breast cancer. Rep Pract Oncol Radiother. 2022;27(3):583-588. doi:10.5603/RPOR.a2022.0064