Levels of post-chemotherapy biomarker for distant metastatic recurrence vary by race
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SAN ANTONIO — Levels of a prognostic biomarker for distant metastatic recurrence varied by race among a subset of women who received neoadjuvant chemotherapy, according to study results presented at San Antonio Breast Cancer Symposium.
An analysis of patients with ER-positive, HER2-negative primary breast cancer showed residual tumors from Black patients had higher biomarker scores than white patients, findings showed.
“Black women with breast cancer are more likely to be diagnosed with advanced-stage disease, have lower access to care and have triple-negative disease, all of which contribute to higher mortality rates compared with white women,” Maja H. Oktay, MD, PhD, professor and co-leader of the tumor microenvironment and metastasis program at Montefiore Einstein Cancer Center, as well as professor of pathology at Albert Einstein College of Medicine, said in a press release. “The results from our study demonstrate differences in the tumor microenvironment of Black women that may partly explain the racial disparities in the outcomes of ER-positive/HER2-negative breast cancer, the most common breast cancer subtype in both white and Black women.”
Background
Oktay and colleagues previously identified three-cell structures in primary breast tumors in which an invasive tumor cell partially inserted into a blood vessel wall is bound to an endothelial cell and a macrophage.
The investigators describe these structures as tumor microenvironment of metastasis (TMEM) doorways because they act as “portals” that allow tumor cells to enter the bloodstream, Oktay said.
The TMEM doorway score — which measures density of TMEM doorways in primary untreated tumors — is prognostic for distant metastatic recurrence among patients with ER-positive, HER2-negative breast cancer.
In addition, the investigators’ prior work showed neoadjuvant chemotherapy increases TMEM doorway scores and results in pro-metastatic changes in the tumor microenvironment for some women.
“Although numerous prospective clinical trials and population-based studies have shown that chemotherapy reduces the risk [for] recurrence and death when given before or after surgery to patients with locally advanced breast cancer and prolongs survival for patients with metastatic breast cancer, we suspect that — in some patients — neoadjuvant chemotherapy may prime the tumor to more efficiently disseminate tumor cells into the blood stream,” Oktay said. “Identifying this mechanism of resistance may allow us to develop new treatment strategies to reverse it.”
Methodology
Oktay and colleagues performed a multi-institutional retrospective study of TMEM doorway scores and macrophage density among patients with unilateral invasive breast cancer who underwent neoadjuvant chemotherapy.
Investigators evaluated whether TMEM doorway scores offered prognostic information about residual disease after neoadjuvant chemotherapy. They also assessed whether TMEM doorway scores in residual disease varied by race.
The analysis included 183 patients who self-identified as Black (n = 96) or white (n = 87).
Researchers used validated multiplex staining and automated scoring methods to determine TMEM doorway scores in residual breast cancer tissues after neoadjuvant chemotherapy. They also assessed relationships between TMEM scores, macrophage density and distant RFS.
Results
Black women appeared more likely than white women to develop distant recurrence (49% vs. 34.5%), undergo mastectomy (69.8% vs. 54%) and have higher-grade tumors.
An analysis of patients with ER-positive, HER2-negative disease showed more macrophages and higher TMEM doorway scores in tumors from Black patients than white patients. Investigators did not observe this disparity in tumors from patients with triple-negative disease.
Analyses adjusted for several factors — including age, race, and tumor size, grade and subtype — showed an association between high TMEM doorway score and shorter distant RFS.
In the overall cohort, patients with high TMEM scores exhibited approximately twice the risk for distant recurrence as those with low or intermediate TMEM scores (HR = 2.01; 95% CI, 1.17-3.44). Researchers observed a similar trend in the subgroup of patients with ER-positive, HER2-negative disease; however, the difference did not reach statistical significance (HR = 2.33; 95% CI, 0.96-5.67). Investigators observed no association between high TMEM score and elevated risk for distant RFS among women with triple-negative breast cancer.
Researchers acknowledged study limitations, including the fact they did not assess TMEM doorway scores prior to neoadjuvant chemotherapy. In addition, the study did not show that chemotherapy increases the number of TMEM doorways more among Black women than white women.
“Our study provides a potential explanation for the persistent racial disparities in ER-positive/HER2-negative breast cancer outcomes that are not fully explained by disparities in social determinants of health, including access to care or treatment,” Oktay said.
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Karadal B, et al. Abstract GS1-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022; San Antonio.
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