Location of Receipt of Initial Treatment and Outcomes in Long-Term Breast Cancer Survivors

<div><p>Purpose</p><p>Cancer outcomes differ depending on where treatment is received. We assessed differences in outcomes in long-term breast cancer survivors at a specialty care hospital by location of their initial treatment.</p><p>Methods</p><p>We retrospectively examined a cohort of women diagnosed with invasive early-stage breast cancer who did not experience recurrence for at least 5 years after the date of diagnosis and were evaluated at The University of Texas MD Anderson Cancer Center between January 1997 and August 2008. The location of initial treatment was categorized as MD Anderson (MDA-treated) or other (OTH-treated). Outcomes analyzed included recurrence-free survival (RFS), distant relapse-free survival (DRFS), and overall survival (OS). The Kaplan-Meier product-limit method was used to compare outcomes between the two groups. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).</p><p>Results</p><p>We identified 5,091 breast cancer survivors (median follow-up 8.6 years), of whom 89.1% were MDA-treated. The 10-year OS, RFS, and DRFS rates were 90.9%, 88.4%, and 89.0% in the MDA-treated group and 74.3%, 49.8%, and 52.7% in the OTH-treated group, respectively. We observed worse outcomes in the OTH-group in both the univariate analysis and the multivariable analysis (OS: HR = 4.8, 95% CI = 3.9–6.0; RFS: HR = 5.8, 95% CI = 4.8–7.0; DRFS: HR = 5.4, 95% CI = 4.5–6.6).</p><p>Conclusion</p><p>Long-term breast cancer survivors who initiated their treatment at MD Anderson had better outcomes. Location of initial treatment could be an independent risk factor for survival outcomes at specialty care hospitals. This analysis has limitations inherent to retrospective observational studies such as other unmeasured variables may be associated with worse prognosis.</p></div

Demographic and clinical characteristics of breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).

<p>Demographic and clinical characteristics of breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).</p

Kaplan-Meier curves for (A) recurrence-free survival (RFS), (B) distant relapse-free survival (DRFS), and (C) overall survival (OS) for breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).

<p>Kaplan-Meier curves for (A) recurrence-free survival (RFS), (B) distant relapse-free survival (DRFS), and (C) overall survival (OS) for breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).</p

Survival and recurrence outcomes in breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).

<p>Survival and recurrence outcomes in breast cancer survivors who received their initial treatment at our institution (MDA-treated) or elsewhere (OTH-treated).</p

Gene expression levels of the top 50 ranked genes.

<p>Gene expression levels of the top 50 ranked genes.</p

KW-2450_TherAdvMedOncol_Additional_file_5Apr2018 – Supplemental material for Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole

<p>Supplemental material, KW-2450_TherAdvMedOncol_Additional_file_5Apr2018 for Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole by Hiroshi Umehara, Yoshimi Maekawa, Fumito Koizumi, Makiko Shimizu, Toshio Ota, Tamer M. Fouad, Jie Willey, Hidekuni Kaito, Norihiko Shiraishi, Daisuke Nakashima, Shiro Akinaga and Naoto T. Ueno in Therapeutic Advances in Medical Oncology</p

Comparative drug response profile between IBC PDX Bcx017 mouse model and Bcx017 PDXEx tissue model.

<p>A) Actively growing (~200–350 mm3) implants in mice were grouped and treated with the indicated drugs for 21days. The graph summarizes data from a previously published in vivo study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195932#pone.0195932.ref069" target="_blank">69</a>]. B) Tumor cells tagged with a nanoparticle assembly of iron oxide and iron nanoparticles cross-linked with poly-L-lysine (NanoshuttleTM) were bio-printed into ultra low attachment plates. The PDXEx bio-print was treated with the indicated drugs at the indicated dose range for 5 days.</p

Comparison of genes either similarly or differentially expressed.

<p>(A) Entire gene set divided into 4 quantiles based on their level of expression to enable determination percentage of similarly expressed genes and differentially expressed genes. (B) Coding gene set divided into 4 quantiles based on their level of expression to enable determination percentage of similarly expressed genes and differentially expressed genes.</p

Lead candidates identified from a high throughput drug screen utilizing the PDXEx screening platform.

<p>A high throughput small molecule screen was performed utilizing the Bcx087 triple negative PDXEx screening platform and the small molecule Anti-Cancer 386 Compound Library (Selleckchem). The ex vivo tumor tissue array was incubate with the drugs at 37oC for 5 days. The top hits were identified as agents having a superior anticancer effect to that of docetaxel and doxorubicin at 250nM.</p

Tissue characteristics of the ex-vivo tumor model.

<p>(A) Bio-printing cells–Tumor cells tagged with a nanoparticle assembly of iron oxide and iron nanoparticles cross-linked with poly-L-lysine (NanoshuttleTM) were dispensed into an ultralow attachment 96 well tissue culture plate placed on a 96 well magnetic drive (n3D Biosciences, Inc). (B) Morphology (4x magnification) of the ex-vivo tumor tissue prints after 5 days of growth at 37°C revealing uniformly sized structures. (C) Proliferative capacity of the PDXEx tissue following 5 days of culture at 37°C.</p