Differential Distant Recurrence Risk by BCI and RS
Multigene assays have been incorporated into the management of patients with node-negative hormone receptor-positive breast cancer for determining adjuvant treatment strategies. To compare prognostic accuracy of two multigene assays, Sestak and colleagues examined cross-stratification between Breast Cancer Index (BCI) and the 21-gene recurrence score (RS) in the TransATAC study. The findings show that BCI demonstrates increased prognostic accuracy versus RS. BCI restratified women with low and intermediate risk by RS into clinically relevant risk groups with significantly different risks of distant recurrence. These findings indicate that BCI may have potential impact to improve individualized risk stratification for patients with early-stage breast cancer.
Reactive Breast Cancer and Stromal Content
Dennison and colleagues evaluated the associative effects of breast cancer with the tumor microenvironment and its influence on tumor behavior. The reactive subtype of breast cancer, identified by reverse-phase protein arrays to have high expression of ECM proteins, was demonstrated to indicate a favorable outcome. The lowest risk tumors, typically ER+ER2− breast cancer, were more likely to have high expression of stromal proteins, high intratumoral stromal volume, and increased cell density within the stromal compartment.
Preclinical Efficacy of DS-8201a, a Novel HER2-Targeting ADC
Antibody–drug conjugates (ADC) have become a promising anticancer agent. Ogitani and colleagues generated and evaluated a novel HER2-targeting ADC called DS-8201a, with a DNA topoisomerase I inhibitor. It showed potent antitumor activity against T-DM1-insensitive tumors and HER2 low-expressing tumors due to the different mechanism payload from T-DM1 and higher a drug-to-antibody ratio than T-DM1. Moreover, favorable pharmacokinetic and safety profiles in monkeys were observed. These data suggest that DS-8201a is an attractive and promising HER2-targeting ADC, which provides an additional treatment option for current HER2-targeting therapy.
TAK-264 in Advanced Gastrointestinal Malignancies
Antibody–drug conjugates directed at specific antigens preferentially expressed on cancer cells are gaining traction in the clinic. Here, Almhanna and colleagues perform the first-in-human phase 1 study investigating TAK-264 targeting guanylyl cyclase, a transmembrane cell-surface receptor expressed in many gastrointestinal cancers. The results demonstrate a manageable safety profile at the maximum tolerated dose, preliminary evidence of antitumor activity, and early signs of clinical benefit in patients with pancreatic, esophageal, and gastric carcinoma.
- ©2016 American Association for Cancer Research.