Background We investigated differences in breast cancer mortality between younger (<40 yrs) and older (≥40 yrs) women by stage at diagnosis to identify patient and tumor characteristics accounting for disparities. Study Design We conducted a retrospective study of women diagnosed with breast cancer in the 1988-2003 Surveillance, Epidemiology, and End Results (SEER) Program data. Multivariate Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to compare overall and stage-specific breast cancer mortality in women <40 yrs and women ≥40 yrs, controlling for potential confounding variables identified in univariate tests. Results Of 243,012 breast cancer patients, 6.4% were <40 yrs, while 93.6% were ≥40 yrs. Compared with older women, younger women were more likely to be Black, single, diagnosed at later stages, and treated by mastectomy. Younger women had tumors that were more likely to be higher grade, larger size, ER/PR negative, and lymph-node positive (p<0.001). Younger women were more likely to die from breast cancer compared with older women (cHR 1.39, CI 1.34-1.45). Controlling for confounders, younger women were more likely to die compared with older women if diagnosed with Stage I (aHR 1.44, CI 1.27-1.64) or Stage II (aHR 1.09, CI 1.03-1.15) disease and less likely to die if diagnosed with Stage IV disease (aHR 0.85, CI 0.76-0.95). Conclusions Higher breast cancer mortality in younger women was attributed to poorer outcomes with early stage disease. Further studies should focus on specific tumor biology contributing to the increased mortality of younger women with early stage breast cancer.

Analysis of the 1988-2003 SEER data indicated that extirpation of the primary breast tumor in patients with stage IV disease was associated with a marked reduction in risk of dying after controlling for variables associated with survival.

RationaleStrategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.MethodsWe analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent.ResultsPatients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.ConclusionOligo- and poly- metastasis are distinct entities at the clinical and molecular level.

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An important mechanism by which pancreatic cancer avoids anti-tumor immunity is by recruiting regulatory T cells (Treg) to the tumor microenvironment. Recent studies suggest that suppressor Treg and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Since IL-6 in the presence of TGF-β has been shown to inhibit Treg development and induce Th17 cells, we hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression. Pan02 murine pancreatic tumor cells that secrete TGF-β were transduced with the gene encoding IL-6. C57BL/6 mice were injected subcutaneously with wildtype (WT Pan02), empty vector (EV Pan02), or IL-6 transduced Pan02 cells (IL-6 Pan02) to investigate the impact of IL-6 secretion in the tumor microenvironment. Mice bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and better overall median survival compared with mice bearing WT or EV Pan02 tumors. Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4+IL-23R+ cells and CD4+IL-17+ cells) in tumors of the IL-6 Pan02 group compared with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4+ tumor-infiltrating lymphocytes was substantiated at the cellular level by flow cytometry and ELISPOT assay, and mRNA level for RORγt and IL-23 receptor by RT-PCR. Thus, the addition of IL-6 to the tumor microenvironment skews the balance toward Th17 cells in a murine model of pancreatic cancer. The delayed tumor growth and improved survival suggests that induction of Th17 in the tumor microenvironment produces an anti-tumor effect.