No abstract

The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, the majority of mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs due to chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic insight may be used to improve selection of future anti-mitotic drugs and to identify a biomarker with which to select patients likely to benefit from paclitaxel.

BACKGROUND To the authors' knowledge, few studies to date have evaluated the effects of survivorship care planning on the care transition process from specialty cancer care to self‐management and primary care, patient experience, or health outcomes. The Patient‐owned Survivorship Transition Care for Activated, Empowered survivors (POSTCARE) is a single coaching encounter based on the Chronic Care Model that uses motivational interviewing techniques to engage survivors of breast cancer. The current study examined the effects of the POSTCARE intervention on patient outcomes and care coordination. METHODS A total of 79 survivors of American Joint Commision on Cancer TNM System stage 0 to IIIB breast cancer were randomized to POSTCARE (40 patients) or usual care (39 patients). Patient outcomes were assessed using the 36‐Item Short Form Health Survey (SF‐36), Social/Role Activities Limitations, Self‐Efficacy for Managing Chronic Disease 6‐Item Scale, the Patient Activation Measure–Short Form, and Patient Health Questionnaire depression scale at baseline and at 3‐month follow‐up. Care coordination was assessed using confirmed primary care physician visits and reported discussion of the survivorship care plan at the 3‐month follow‐up. Logistic and linear regression analyses were conducted to examine the effect of POSTCARE on selected outcomes. RESULTS Participants in the intervention group versus those receiving usual care demonstrated significantly higher self‐reported health (F‐statistic (3,71), 3.63; P =.017) and lower social role limitations (F (3,70), 3.82; P =.014) and a trend toward greater self‐efficacy (F (3,69), 2.51; P = .07). Three quality‐of‐life domains reached clinically meaningful improvement at the 3‐month follow‐up, including physical role (P =.0009), bodily pain (P =.03), and emotional role (P =.04). CONCLUSIONS The POSTCARE intervention appeared to have a positive impact on patient outcomes and demonstrated promise as a strategy with which to improve survivors' experience, care coordination, and health outcomes. Cancer 2016;122:3232–42. © 2016 American Cancer Society.

A navigator-led ACP program was feasible and may be associated with lower rates of resource utilization near EOL.

Costs to Medicare and health care use from 2012 through 2015 declined significantly for navigated patients compared with matched comparison patients. Lay navigation programs should be expanded as health systems transition to value-based health care.