Background: Clinical trials have demonstrated that the 21-gene assay (Oncotype DX) can predict the benefits of adjuvant chemotherapy in patients with hormone receptor-positive (HR+) and human epidermal growth factor 2-negative (HER2−) breast cancer. This study investigated the real-world utilization of this genomic test in Taiwanese patients. Materials and Methods: We compiled data on the recurrence score (RS) and clinicopathological characteristics of patients who received the 21-gene assay between August 2016 and August 2021. Survival outcomes were analyzed using the Kaplan–Meier method and log-rank test. Correlations between clinicopathological characteristics and RSs were analyzed using the Chi-square test or Fisher's exact test. Results: Of the 106 recruited patients, 34 and 72 were classified into different risk groups using conventional and Trial Assigning Individualized Options for Treatment (TAILORx)-based cutoff points, respectively. In the conventional stratification group, 61.8%, 29.4%, and 8.8% of the patients were classified into the low-risk (RS: 0–17), intermediate-risk (RS: 18–30), and high-risk (RS: 31–100) categories, respectively. In the TAILORx stratification group, 18.1%, 72.2%, and 9.7% of the patients were classified into the low-risk (RS: 0–10), intermediate-risk (RS: 11–25), and high-risk (RS: 26–100) categories, respectively. In survival analysis, recurrence-free survival did not significantly differ among discrete risk categories. The high-risk category determined using TAILORx-based cutoff points was associated with the presence of >14% Ki-67-positive cells (P = 0.004) and tumor histology Grade III (P = 0.001). Conclusion: Using the Oncotype DX assay, we classified a small proportion of our Taiwanese patients into the high-risk category; no survival difference was observed among the patients in distinct risk categories. These results suggest the clinical utility of the 21-gene assay in Taiwanese patients with early HR+/HER2−breast cancer.

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.

Background Sentinel lymph node biopsy (SLNB) is standard approach of axillary region for early breast cancer patients with clinically negative node. The present study investigated patients with false-negative sentinel nodes (FNSN) of intraoperative frozen section.Methods A case-control study with 1:3 ratio was conducted. FNSN was diagnosed as negative sentinel nodes (SNs) in frozen sections, but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) blocks. Control was defined no metastasis of SNs in both frozen and FFPE sections.Results Total 20 FNSN cases and 60 matched-controls were enrolled from 333 SLNB patients between April 1, 2005 and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had a larger tumor size in preoperative mammography and more lymphatic tumor emboli in core biopsy (P-value 0.033 and < 0.001, respectively). Four FNSN patients had metastasis in the non-relevant SNs. Other 16 FNSN patients had results of benign lymphoid hyperplasia of SNs in frozen sections and metastasis in FFPE blocks. Micrometastasis (less than 2 mm) was detected in seven of 16 patients and metastases in non-sentinel nodes was recognized in two of 16 patients. All FNSN patients received second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed recurrence of breast cancer. The disease-free survival, disease-specific survival, and overall survival in FNSN were non-inferior than controls.Conclusion Outcomes of FNSN patients after completing ALND was non-inferior to those without metastasis in SNs. ALND improved survival of patients with metastasis non-sentinel ALNs. However, omitting ALND had no effect for those have only micrometastasis in SNs.

Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood–cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pulldown and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.

Background: Sentinel lymph node biopsy (SLNB) is the standard approach of the axillary region for early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes of intraoperative frozen section (FNSNs) in real-world data.Methods: A case–control study with a 1:3 ratio was conducted. FNSN was diagnosed when sentinel nodes (SNs) are negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections.Results: A total of 20 FNSN cases and 60 matched controls were enrolled from 333 SLNB patients between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had larger tumor sizes in preoperative mammography (P = 0.033) and more lymphatic tumor emboli in core biopsy (P < 0.001). Four FNSN patients had metastasis in the non-relevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from the FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in non-relevant SNs were recognized in two patients. All FNSN patients received a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed recurrence of breast cancer. The disease-free survival, disease-specific survival, and overall survival in FNSN were not inferior to the controls.Conclusions: The patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, outcomes of FNSN patients after completing ALND were noninferior to those without metastasis in SNs. ALND provides a correct diagnosis of patients with metastasis in non-sentinel axillary lymph nodes.