A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

Circulating cancer-associated macrophage-like cells and macrophage-related cytokines in obese patients with advanced breast cancer who undergo neoadjuvant chemotherapy.

Purpose: Cancer-associated macrophage-like cells (CAMLs) are rare, gigantic, and atypical circulating cells found exclusively in the peripheral blood of patients with solid cancers. Obesity-induced hypoxia attracts macrophages to the tumor microenvironment, where they contribute to establishing chronic inflammation, leading to cancer progression. We hypothesized that obese patients with advanced breast cancer may have CAML profiles different from those of nonobese patients, and these profiles may correlate with proinflammatory markers or other macrophage-related markers. Methods: We prospectively collected 20 mL of peripheral blood from patients diagnosed with stage 2-4 breast cancer. We identified CAMLs using the CellSieve microfiltration system and in parallel quantified the proinflammatory and macrophage-related markers using a multiplex cytokine panel. We further evaluated C-X-C chemokine receptor type 4 (CXCR4) expression in CAMLs to investigate its relationship to the macrophage differentiation. We estimated the association between CAML characteristics and body mass index (BMI), body composition, and cytokines/chemokines. Results: Thirty patients were included in the study, and 28 samples were analyzed. Higher BMI was significantly correlated with the increased maximum CAML size (P = 0.035). Patients with higher BMIs had significantly increased macrophage-colony stimulating factor (M-CSF) levels in plasma (P = 0.007), and obese patients trended towards higher tumor necrosis factor-alpha, MIP-1α and M-CSF expression (P <0.10). Body composition analysis showed that the M-CSF and SAT amounts were significantly correlated (P = 0.010). MIP-1α expression was significantly correlated with average CXCR4 CAML expression (P = 0.003). Conclusion: We discovered larger CAML size was associated with SAT-dominant obesity with increased macrophage-related and proinflammatory markers in obese than in nonobese breast cancer patients.

Changes in Overall Survival over Time for Patients with de novo Metastatic Breast Cancer.

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. In addition, median OS was significantly longer in patients with non-inflammatory breast cancer (p = 0.02) and patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all p < 0.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for the ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy.

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.