Race and Immune Microenvironment Impacts on Breast Cancer Outcomes

Breast cancer outcomes are significantly impacted by race and immune responses, particularly among Black patients with triple-negative subtypes,emphasizing the need to understand these disparities and develop more effective treatment strategies. | Image Credit: ST.art - stock.adobe.com

Immune markers and racial differences play a crucial role in breast cancer prognosis and treatment response, as demonstrated in 2 posters presented at the San Antonio Breast Cancer Symposium 2024.^1,2

The first poster compared the impact of stromal tumor-infiltrating lymphocytes (sTILs) on outcomes for Black and non-Black patients.¹

Black women are more likely to develop triple-negative breast cancer (TNBC) and have a higher likelihood of dying. Previous research analyzed genetics from over 40,000 women of African descent, and 18,000 of them had received a diagnosis of breast cancer.³ About 85% of participants were African Americans, while the rest of the population were from Barbados or Africa.

Neoadjuvant chemotherapy is the standard-of-care treatment for patients with early-stage TNBC.¹ Responses to neoadjuvant chemotherapy and the long-term outcomes in TNBC are measured by immune response parameters. Indicators of the systemic immune environment may include circulating blood cell counts that contribute to the response.

Patients with stages I to III TNBC (n = 469) who previously received neoadjuvant chemotherapy (n = 321) or neoadjuvant chemotherapy combined with pembrolizumab (n = 148) were enrolled in the prospective cohort trial between 2011 to 2023.

Majority of the patients were White (81%), followed by patients who were Black (14%), Hispanic (4%), and Asian (2%). Out of the 469 patients enrolled, 33% had node-positive disease. Higher tumor stages (P = .005) and TNM stages (P = .004) were more likely among patients who received neoadjuvant chemotherapy combined with pembrolizumab. This population also had a shorter follow-up duration compared with patients who only received neoadjuvant chemotherapy.

Black patients reported a reduced absolute neutrophil count (median 3.6 vs 4.6 k/uL) and neutrophil to lymphocyte ratio (median 1.6 vs 2.5) compared with non-Black patients. Black patients also had higher absolute lymphocyte count (median 2.2 vs 1.8 k/uL) and lymphocyte to monocyte ratio (median 4.4 vs 3.8) compared with non-Black patients.

The higher lymphocyte count "could be related to higher underlying chronic systemic inflammation and higher BMI in Black compared to non-Black patients,” the researchers theorized. Chronic inflammation and obesity are interlinked and known to enact proinflammatory cytokines.

More than half (n = 257) of the population had sTIL counts available and Black patients had higher sTILs compared with non-Black patients (median 40% vs 10%). Additionally, pathologic complete response rates were similar between Black and non-Black patients.

The only circulating blood cell components included the independent impact monocytes have on recurrence-free survival (RFS), demonstrating worse TNBC outcomes with higher monocytes. Black patients have an increased likelihood of having immune-enriched tumors with a more unfavorable peripheral white blood cell immune environment.

Improved pathologic complete response (pCR) rates and RFS among Black populations may not be translated by sTILs based on the unfavorable peripheral white blood cell immune environment, the impact of obesity/chronic inflammation on tumor immune microenvironment, and white blood cell immune environment.

Future studies should look to examine the interaction between T-cell immunoglobulin, circulating monocytes, and race and how these interactions impact response to therapy.

The second poster analyzed TILs and responses to neoadjuvant chemotherapy in young patients with breast cancer.² The study authors examined immune infiltration in breast tumors of young women undergoing neoadjuvant chemotherapy associated with clinicopathologic features and treatment response.

Immune inflammatory biomarkers can identify various malignant tumors through the levels of neutrophil, platelet, monocyte, and lymphocyte, along with ratios of these biomarkers.⁴ When specific biomarkers are identified, improved clinical outcomes are more likely.

The Young Women’s Breast Cancer Study (NCT01468246) was a prospective cohort study that included patients with stage I to III breast cancer who previously received neoadjuvant chemotherapy with pretreatment tumor tissue.² Majority of the population was White (82%), followed by Asian (7.7%), Black (2.6%), Multiracial (2.6%), and other (4.6%). Over half of the population was between 36 and 40 years old (53.6%), with stage III breast cancer (62.9%) and tumor grade 3 (70.6%).

Higher infiltration of certain TIL subtypes within stroma and tumor cells was found among patients with recent pregnancies (≤ 5 years ago), BRCA1 mutations, and tumors that were grade 3, stage III, and HER2-positive or TNBCs. There were no significant differences in TILs based on age, race, or ethnicity.

Patients that achieved a pCR had better stromal T regulatory, intratumoral T helper, and intratumoral PD-L1–positive cell infiltration. Higher levels of stromal T regulatory cells and all intratumoral TIL subtypes are predictive of pCR following alterations for breast cancer stages, grades, and subtypes.

Results concluded the relationship between TILs and pCR among young women possesses unique clinicopathologic features linked to increased tumor immunogenicity.

“Characterization of immune subpopulations could help refine the predictive value of TILs in young patients with breast cancer, who may benefit from individualized escalated and de-escalated neoadjuvant treatment strategies,” the researchers wrote.

These studies highlight the complex interplay between race, immune response, and breast cancer outcomes, emphasizing the need for further research to address racial disparities and develop more effective treatment strategies for all patients.

“Future research should delve deeper into young patient factors like recent pregnancy, BRCA1/2 mutation status, and that impact of those factors on TIL infiltration. With that, we might be able to sort of identify immunogenic subgroups that may benefit more from immunomodulatory strategies, or from deescalated or individualized treatment strategies,” commented Megan Tesch, MD, lead study author and medical oncologist at Dana-Farber Cancer Institute, in an interview with Pharmacy Times^®.

References

1. Yoder R, Staley JM, Fernandez I, et al. Impact of racial differences in circulating blood components and stromal tumor-infiltrating lymphocytes (sTILs) on outcomes in triple negative breast cancer (TNBC). Presented at: San Antonio Breast Cancer Symposium 2024; December 10-13, 2024; San Antonio, Texas. Poster PS1-01.
2. Tesch ME, Guzman-Arocho YD, Collins LC, et al. Tumor-infiltrating lymphocytes (TILs) and response to neoadjuvant chemotherapy (NACT) in young patients with breast cancer. Presented at: San Antonio Breast Cancer Symposium 2024; December 10-13, 2024; San Antonio, Texas. Poster PS1-04.
3. Contie V. Gene variants and breast cancer risk in Black women. NIH. June 3, 2024. Accessed December 10, 2024. https://www.nih.gov/news-events/nih-research-matters/gene-variants-breast-cancer-risk-black-women
4. Li F, Wang Y, Dou H, Chen X, Wang J, Xiao M. Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy. Front Oncol. 2024;14:1349021. Published 2024 Feb 6. doi:10.3389/fonc.2024.1349021