Compartmental Syndecan-1 (CD138) expression as a novel prognostic marker in triple-negative metaplastic breast cancer.

BACKGROUND: Metaplastic breast cancer (MpBC) is rare, aggressive, and mostly triple-negative (TN) subtype of BC. We aimed to investigate the potential prognostic significance of Syndecan-1 (SDC1/CD138) expression in this unique tumor. METHODS: Archived charts of 50 TNBC patients [21 MpBC and 29 invasive ductal carcinoma (IDC)] were retrospectively evaluated. Corresponding paraffin blocks were used for immunohistochemical (IHC) staining of SDC1. Compartmental (epithelial membranous, stromal, and cytoplasmic) staining scores were expressed in quartiles (Q) and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: The median follow-up period was 54.6 months (range: 2.2-112.7). MpBC patients showed significantly worse DFS and OS than IDC (p = 0.007 and 0.004, respectively). MpBC demonstrated significantly higher Q4 stromal and membranous SDC1 compared to IDC (p = 0.016 and 0.021, respectively), whereas IDC exhibited significantly higher cytoplasmic Q4 SDC1 than MpBC (p = 0.015). Stromal Q4 SDC1 expression was found to be an independent factor associated with MpBC relative to IDC (OR: 6.7, 95% CI: 1.24-36.90; p = 0.028). Stromal Q4 SDC1 expression was also an independent prognostic parameter for worse DFS and OS compared to Q1-3 in the whole cohort (HR: 4.2, 95% CI: 1.6-10.5; p = 0.003 and HR: 5.8; 95% CI: 2.2-15.3; p < 0.001, respectively). In MpBC, cytoplasmic Q1-3 SDC1 expression was an independent prognostic indicator for worse OS compared with their IDC counterparts (HR: 2.837, 95% CI: 1.048-7.682; p = 0.04). CONCLUSION: This study suggests, for the first time, that differential expression and localization of SDC1 may contribute to the pathogenesis and prognosis of TN-MpBC. Therefore, targeting SDC1 (CD138) could emerge as a novel therapeutic approach for this devastating disease.

The conundrum of metaplastic breast cancer: a single Egyptian institution retrospective 10-year experience (2011-2020).

BACKGROUND: Metaplastic breast cancer (MetBC) still represents a conundrum owing to its peculiar histogenesis and molecular drivers that render it extremely resistant to standard chemotherapy with ultimate dismal survival. AIM: Describe the Egyptian National Cancer Institute's (NCI-E) experience with MetBC regarding its clinicopathologic features, treatment, and survival outcomes. PATIENTS AND METHODS: Between 2011 and 2020, all MetBC patients presented to NCI-E were retrospectively evaluated. Original clinicopathologic data, therapeutic modalities, pathologic response to neoadjuvant chemotherapy (NACT), recurrence, and date of last follow-up/death were obtained from archived charts. RESULTS: A cohort of 135 females, the median age was 52 years, and median follow-up period was 40 months (range: 2.6-130.8). Two-thirds were triple negative (TN). Squamous carcinoma was prevalent in 74.8% followed by carcinoma with osseous/chondroid differentiation, spindle cell, and low-grade adenosquamous carcinoma encountered in 13.3, 7.4, and 4.5%, respectively. Modified radical mastectomy was done in 59.3%, and positive nodes (pN+) were depicted in 37.7%. Median Ki-67 was 45% (range: 10-88); grade III and lymphovascular invasion (LVI) were observed in 83.7 and 43.7%, respectively. Stage II was the most common (49%), whereas initial stage IV was encountered in 8.1%. Anthracyclines/taxane combinations were rampant in adjuvant/neoadjuvant settings. The latter was employed in 41 patients, with only 3 cases (7.3%) achieving pathologic complete response (pCR), while moderate/significant residual tumor burden was found in 83%. The 5-year DFS and OS were 56.4 and 57.6%, respectively. Spindle cell carcinoma showed the worst survival parameters in univariate analysis. On the multivariate level, higher tumor stage (pT3 & 4), Ki-67 ≥ 45%, and TN subtype were independent variables for worse DFS and OS; age ≥ 52 years and the presence of LVI were independent features for worse DFS, whereas pN+ was an independent parameter for worse OS. CONCLUSIONS: This study further solidifies the dreadful response of MetBC to conventional chemotherapy regimens employed in common non-metaplastic pathologies. A radical shift in treatment standards tailored to combat the molecular landscape of this distinctive tumor is urgently needed. Immunotherapy and molecularly targeted agents demonstrated promising results in phase I and II trials with hopeful sooner implementation in phase III studies.

Localized Wilms' tumor in low-middle-income countries (LMIC): how can we get better?

BACKGROUND: Wilms' tumor (WT) represents about 6% of all childhood cancers. The overall survival markedly improved to exceed 90% in developed countries, yet some studies from developing counties still have poorer outcomes. The aim of this study is to assess the clinical outcome and the different prognostic factors that influence the outcome of pediatric loco-regional WT cases treated at National Cancer Institute (NCI), Cairo University, Egypt. This is a retrospective study which included pediatric loco-regional WT patients presented between January 2008 and December 2017. Patients were followed up till June 2019. RESULTS: Ninety-two eligible patients were included. Median age was 3 years (range 1 month-9 years). Abdominal mass was the commonest presentation (72.8%). The 5-year EFS and OS of the whole group was 83.7% and 94.6% retrospectively. Despite having a similar EFS (84.8 vs. 82.6%), stage III patients had a significantly lower OS than those in stages I and II (89.1% vs. 100%, p value 0.024). Twelve patients had unfavorable histology and had a significantly lower EFS and OS than the patients with favorable histology (50 and 83.3% vs. 88.8 and 96.3%, p value < 0.001 and 0.043, respectively). CONCLUSION: Loco-regional Wilms' tumor cases treated in Egypt had OS nearly the same as in developed countries, but had a lower EFS than expected mainly stages I and II. The stage and histological type are the main factors influencing the survival, and further studies are needed to investigate nuclear unrest grades and proper management of such cases.