Disparities in the TME of African American Patients with Breast Cancer Requires More Targeted Therapy

African American women with triple negative breast cancer (TNBC) experience phenotypically more aggressive disease associated with a poorer prognosis due to variances in their tumor microenvironment (TME). Therefore, it is important for this patient population to have access to targeted treatments but disparities in cancer care remain a barrier for African American women with TNBC.

In a review of current therapies and ongoing trials that could impact the TME for African American patients with TNBC, researchers discussed how compared with White women with breast cancer, the mortality rate among African American patients with breast cancer is 42% higher despite having a lower overall incidence of breast cancer.¹ This is due, in part, to African American patients with breast cancer having a higher incidence of TNBC, making up 21% of breast cancer cases in this patient population while TNBC represents approximately 10% of all breast cancer diagnoses.

Across several cancer types, treatment disparities persist for African American patients and when compared with other ethnic groups of patients mortality rates remain the highest among African American women. The researchers noted that there is no consensus on a single reason for these disparities but that multiple factors are at play, which include patients having an advanced stage of cancer at diagnosis, limited access to new treatments, and a higher likelihood to be impacted by socioeconomic disadvantages. In the review, the researchers also highlighted that different genetic and physiological factors can play a role in the severity of disease for African American women with breast cancer that impact cytokines, which activate oncogenic pathways.

For example, compared with White women, the incidence of obesity in African American women is 49.6% vs 42.2%. Studies have shown that obese patients have higher plasma levels of proinflammatory cytokines like resistin, IL-6, and CXCL8. This predisposing factor for cancer in patients means that potentially more African American women than White women have a TME that could develop cancer. Positive correlation has been previously seen between plasma resistin levels, the size, and stage of cancerous breast tumors and rate of lymph node metastasis, therefore, having more of these cytokines active can lead to advanced TNBC in patients.

The TME of African American women also differs from White women when the researchers looked at IL-6. This is also an activated cytokine associated with obesity in patients, but overall African American women have more IL-6 than White women. IL-6 is an important cytokine within the patient’s TME that leads to immunoediting of the tumor immune microenvironment (TIME), but IL-6 and resistin are a part of feedback loop. This means that as the levels of 1 increases, the level of the other does as well. The researchers explained that these disparities among cytokines, like IL-6 and resistin, impact the stage and effects of disease in patients. In order to be treated better, these patients need targeted treatments and access to this novel treatment.

Reviewing currently available data and trial set up from 26 active trials that looked at IL-6 inhibition, JAK inhibition, STAT inhibition, VEGF inhibition, immune checkpoint inhibitors, and adoptive cell transfer bated therapy. Many of these therapies are novel or looking to incorporate known treatments, like chimeric antigen receptor T-cell therapy, into the treatment of patients with TNBC or advanced stage breast cancer. For example, sarilumab (Kevzara), a monoclonal antibody therapy, is under investigation in a dose finding phase 1 trial (NCT04333706) in combination with capecitabine for patients with stage I-III TNBC.

According to the researchers, these treatments present a unique opportunity to target the atypical TME in African American women with breast cancer to decrease morbidity and even provide treatment for patients that may harbor chemokine and cellular imbalances. However, they reiterate that it is vital to close the disparity gaps for this patient population by enrolling more African American patients into these crucial trials.

^Reference

^{Zajac K, Malla S, Babu R, et al. Ethnic disparities in the immune microenvironment of triple negative breast cancer and its role in therapeutic outcomes. Cancer Reports. 2023;e1779. doi.org/10.1002/cnr2.1779}