Impact of Inequities on Delay in Breast Cancer Management in Women Undergoing Second Opinions.

BACKGROUND: Inequities in breast cancer treatment lead to delay in therapy, decreased survival and lower quality of life. This study aimed to examine demographics and clinical factors impacting time to treatment for second-opinion breast cancer patients. MATERIALS AND METHODS: We performed a retrospective chart review to analyze patients presenting to one academic institution for second opinion of breast imaging, diagnosis, or breast-related treatment. Data from women with stage I-III breast cancer who received treatment at this institution were evaluated to determine the impact of patient demographics and clinical characteristics on time to first treatment. RESULTS: Of the 1006 charts reviewed, 307 met inclusion criteria. Low-income patients averaged 58 days from diagnosis to surgery compared to 35 days for high-income patients (incidence rate ratio [IRR] 0.64, P<0.01). Black patients averaged 56 days from diagnosis to surgery compared to 42 days for White patients (IRR 1.37, P<0.01). Latina patients averaged 38 days from initial encounter to neoadjuvant chemotherapy compared to 20 days for White patients (IRR 1.69, P<0.05). CONCLUSION: Patients with low-income, of Black race and Latina ethnicity experienced increased time to treatment. Additionally, time to mastectomy with and without reconstruction was longer than time to partial mastectomy. Further exploration is needed to determine why certain factors lead to treatment delay and how inequities can be eliminated.

Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells.

Glioblastoma (GBM) is the most common, aggressive, and deadly form of adult brain cancer, and is associated with a short survival rate (median 12-15 months, 5+ year less than 5%). The complex tumor microenvironment includes matrix transitions at the tumor margin, such as gradations in hyaluronic acid (HA). In addition, metabolic stress induced by decreased oxygen content across the tumor may contribute to tumor progression. However, cross-talk between matrix composition and metabolic stress remains unclear. In this study, we fabricated an in vitro brain memetic HA-decorated gelatin hydrogel platform incorporating variable oxygen concentrations to mimic intra-tumoral hypoxia. We observed that EGFR status (wildtype vs. a constitutively active EGFRvIII mutant) of U87 GBM cells affected proliferation and metabolic activity in response to hypoxia and matrix-bound HA. The use of an invasion assay revealed that invasion was significantly enhanced in both cell types under hypoxia. Moreover, we observed compensatory secretion of soluble HA in cases of enhanced GBM cell invasion, consistent with our previous findings using other GBM cell lines. Interestingly, U87 GBM cells adapted to hypoxia by shifting toward a more anaerobic metabolic state, a mechanism that may contribute to GBM cell invasion. Collectively, these data demonstrate that the use of a three-dimensional hydrogel provides a robust method to study the impact of matrix composition and metabolic challenges on GBM cell invasion, a key factor contributing to the most common, aggressive, and deadly form of adult brain cancer.