ICAM2 initiates trans-blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer.

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, pull-down 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.

Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative 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.

False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data. METHODS: A case-control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were 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 from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls. CONCLUSIONS: Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

The prognosis of early-stage breast cancer in extremely young female patients.

ABSTRACT: Breast cancer at a young age is associated with poor outcomes. However, few reports have compared the outcomes of breast cancer between extremely young patients and elderly patients.We retrospectively collected information on patients diagnosed with breast cancer before 30 years of age. This case-control study employed matched operative methods, stage, and subtypes with a case-to-control ratio of 1:3. The primary endpoint was disease-free survival, and the secondary endpoint was overall survival. We analyzed potential prognostic factors in univariate and multivariate analyses.This analysis included 18 patients in the young group with a median age of 28.5 years and 54 patients in the control group with a median age of 71 years. The 5-year disease-free survival rate was 68.8% in the former group and 84.6% in the latter group (P = .080). The 5-year overall survival was 87.1% and 91.2% in the young and old groups, respectively (P = .483). Multivariate analysis showed that tumor size and triple-negative breast cancer was major prognostic factors of poorer disease-free survival in the young group.Extremely young breast cancer patients had a trend to develop a poorer disease-free survival than old patients, but not a poorer overall survival. Aggressive treatment for young patients at early stages of disease would improve survival.

Evaluation of the Learning Curve in Robotic Nipple-sparing Mastectomy for Breast Cancer.

BACKGROUND: This study discusses the preliminary results of robotic nipple sparing mastectomy (R-NSM) in patients with breast cancer and analyzes the learning curve of the same surgeon in a single medical center. PATIENTS AND METHOD: Patients with breast cancer from a single center who received R-NSM between 2018 to 2020 were recruited for clinical and pathologic tumor characteristics including family history, grade, type of tumor, treatment, and outcome. The learning curve for R-NSM was analyzed by using cumulative sum (CUSUM). RESULTS: A total of 85 R-NSM procedures from 78 patients were evaluated. In the CUSUM plot analysis of the learning curve, a significant decrease in time for mastectomy, reconstruction, and total operation appeared in the 22nd, 23rd, and 26th procedures, respectively. Patients' body weight, gel implant size, and specimen weight had significant correlations with the time for mastectomy. Four (5.6%) patients had nipple partial ischemia, and 1 (1.4%) had total nipple necrosis. The mean follow-up was 11.4 ± 6.2 months; only 1 patient showed recurrence. CONCLUSION: Robotic breast surgery is a feasible method with good cosmetic outcome under suitable patient selection. Oncologic safety is not a reason to stop its development.