Residual tumors from Black patients with estrogen receptor (ER)-positive/HER2-negative primary breast cancer treated with neoadjuvant chemotherapy have a higher score of a biomarker of distant metastatic recurrence than tumors from White patients.


Black patients with breast cancer have 40% higher death rates compared with White patients.1 In line with this, Black race is associated with higher risk of distant recurrence rate and poorer survival in patients with ER-positive/HER2-negative, but not in triple negative, breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy.2

Previous research showed that neoadjuvant chemotherapy can induce breast cancer metastasis by opening tumor micro-environmental of metastasis (TMEM) doorways.3  These are 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. TMEM doorway density proves to be a prognostic marker of metastasis in patients with breast cancer, especially in ER-positive/HER2-negative disease.4 To evaluate the role of TMEM doorway density in the racial disparity in breast cancer outcome, a retrospective study was conducted. Dr. Burcu Karadal-Ferrena (Albert Einstein College of Medicine) presented the results at the 2022 San Antonio Breast Cancer Symposium.5

The study included 183 patients (96 self-identified as Black, 87 as White) with HER2-negative disease and with residual disease of at least 5 mm after neoadjuvant chemotherapy. Black patients had higher-grade disease (76% vs 65% grade 3), higher rate of distant recurrence (49% vs 42%), and were more likely to undergo mastectomy (70% vs 62%). Automated quantification of TMEM doorway density showed higher scores in ER-positive/HER2-negative Black patients compared with White patients (P=0.0102), but not in TNBC Black versus White patients. In addition, a high TMEM doorway was associated with worse disease recurrence-free survival in all ER-positive/HER2-negative patients, but not in TNBC patients.

Based on these results, Dr. Karadal-Ferrena concluded “High TMEM doorway score is an independent prognostic risk factor in patients with residual disease after neoadjuvant chemotherapy. Racial disparity in outcome may be due to a more pronounced increase in TMEM doorway density after neoadjuvant chemotherapy in Black patients.” A limitation of the study, Dr. Karadal-Ferrena said, was that neither TMEM doorway density at baseline nor change in TMEM doorway score after neoadjuvant chemotherapy were evaluated.

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