Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that is associated with significantly high mortality. In spite of advances in IBC diagnoses, the prognosis is still poor compared to non-IBC. Due to the aggressive nature of the disease, we hypothesize that elevated levels of inflammatory mediators may drive tumorigenesis and metastasis in IBC patients. Utilizing IBC cell models and patient tumor samples, we can detect elevated NF-κB activity and hyperactivation of non-canonical drivers of NF-κB (nuclear factor kappaB)-directed inflammation such as tyrosine phosphorylated receptor-interacting protein kinase 2 (pY RIPK2), when compared to non-IBC cells or patients. Interestingly, elevated RIPK2 activity levels were present in a majority of pre-chemotherapy samples from IBC patients at the time of diagnosis to suggest that patients at diagnosis had molecular activation of NF-κB via RIPK2, a phenomenon we define as “molecular inflammation”. Surprisingly, chemotherapy did cause a significant increase in RIPK2 activity and thus molecular inflammation suggesting that chemotherapy does not resolve the molecular activation of NF-κB via RIPK2. This would impact on the metastatic potential of IBC cells. Indeed, we can demonstrate that RIPK2 activity correlated with advanced tumor, metastasis, and group stage as well as body mass index (BMI) to indicate that RIPK2 might be a useful prognostic marker for IBC and advanced stage breast cancer.

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Background : Urachal carcinoma is a rare malignancy comprising less than 1% of all bladder cancers. The signet-ring cell subtype is particularly aggressive and poses significant diagnostic and therapeutic challenges. Methods: A retrospective review of urachal carcinoma cases from 1989 to 2023 was conducted using data from BC Cancer and MD Anderson Cancer Center. The study analyzed 75 patients, including 28 signet-ring cell carcinoma (SRCC) cases and a control group of 47 non-SRCC cases, to compare survival patterns, treatment outcomes, and histopathological features. Results: Clinically, the SRCC subtype was associated with advanced stage at presentation (pT3/pT4) and a higher recurrence rate (82% vs. 53%; p = 0.01). Survival analysis demonstrated worse outcomes for the SRCC cohort, with a five-year cancer-specific survival (CSS) of 39% compared to 64% in the non-signet group (p = 0.053). Partial cystectomy remained the primary surgical approach for both cohorts. Adjuvant chemotherapy was administered more often in SRCC cases (86% vs. 47%). Conclusions: By providing a comprehensive multi-institutional analysis, this study establishes urachal SRCC as a distinct clinical entity with a strong independent prognostic significance. Despite aggressive multimodal management, it carries a poorer prognosis compared to urachal non-SRCC, emphasizing the need for subtype-specific therapeutic guidelines.