Search

Background Black women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with White women. Adding further risk, older patients with breast cancer are most at risk for treatment modifications; however, it is unclear if this remains true for Black patients. Furthermore, the clinical implications of treatment modifications and delays on survival is uncertain, particularly in Black patients. Patients and Methods The purpose was to investigate whether age was a moderator for the association between treatment modifications (dose held, dose delayed, and early cessation) and overall survival and disease-free survival (DFS) in Black women with breast cancer using a retrospective cohort study of patients with early stage breast cancer treated with adjuvant chemotherapy. Results Across the entire sample (n = 115), 37.4% (n = 43) of patients experienced a treatment modification. There was a significant interaction between age group and held dose for DFS (P = .026). Specifically, those diagnosed at 55 years of age and older, who had doses of chemotherapy held, experienced worse DFS compared with those who did not (hazard ratio, 4.185; 95% confidence interval, 1.187-14.75). In contrast, there was no difference in DFS between those who did and did not have doses held in patients diagnosed below 55 years of age (hazard ratio, 0.626; 95% confidence interval, 0.177-2.218). Conclusion In this study, Black women receiving adjuvant chemotherapy for treatment of early stage breast cancer had roughly equal treatment modifications across age groups. However, held doses of chemotherapy in older Black patients were associated with worse DFS. Age may impact clinical outcomes seen with adjuvant chemotherapy treatment modifications.

Of women diagnosed with metastatic breast cancer (MBC), 20% to 30% survive ≥5 years. We evaluated data from a large breast cancer program to identify features associated with MBC survival.Women diagnosed with MBC in or after 1999 were included. Long-term MBC survival was defined as ≥5 years from date of MBC diagnosis (n = 122), short-term MBC survival as ≤2 years (n = 191). Differences were assessed using t tests, Wilcoxon-Mann-Whitney tests, χLong-term survivors were significantly (P .05) younger, premenopausal, partnered, had estrogen receptor (ER)-positive, progesterone receptor-positive, and HER2-positive disease, lower Charlson Comorbidity Index, lower rates of visceral metastases, and higher household income. After adjustment for potential confounders, de novo MBC, premenopausal status, ER-positive status, and HER2-positive status remained significantly positively associated with long-term survival (respectively: OR, 2.68 [95% confidence interval (CI), 1.48-4.88]; OR, 1.96 [95% CI, 1.02-3.79]; OR, 3.74 [95% CI, 1.72-8.14]; OR, 2.88 [95% CI, 1.61-5.14]). Triple-negative status, visceral with bone metastases, and brain metastases remained negatively associated with long-term survival (respectively: OR, 0.12 [95% CI, 0.05-0.29]; OR, 0.18 [95% CI, 0.07-0.47]; OR, 0.16 [95% CI, 0.04-0.60]). Partner status and household income were significant in univariate but not multivariate analyses.Diagnosis of de novo MBC, premenopausal status, ER-positive status, and HER2-positive status were positively associated whereas triple-negative status, brain metastases, and visceral with bone metastases were inversely associated with long-term survival. These findings can be applied to better prognosticate survival for MBC patients.

Background Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287–395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3′ partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6–7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

BACKGROUND: Symptom distress in women with breast cancer is associated with early discontinuation of chemotherapy and may influence treatment outcomes. Describing racial differences in prechemotherapy symptom distress and examining contextual variables of the symptom experience may inform our understanding of the complex problem of racial disparities in breast cancer. AIM: To determine if perceived social support, healthcare system distrust, and economic hardship predict symptom distress in women with breast cancer prior to their first chemotherapy treatment. DESIGN: Descriptive, correlational, cross-sectional METHODS: Baseline data (N = 119) was used from a multisite, longitudinal study comparing the symptom experience and ability to receive chemotherapy of Black and White women with breast cancer (R01MD012245;Rosenzweig, PI). Measures included the Symptom Distress Scale, Interpersonal Support Evaluation List, Health Care System Distrust Scale, and Psychological Sense of Economic Hardship scale. The analysis consisted of multiple regression and a t-test. RESULTS: On average, participants reported five symptoms prior to chemotherapy. Black women reported higher symptoms distress than White women; t(68.34) = 2.15, p = .035. The model explained 26% of variance in symptom distress; F(5, 112) = 9.01, p < .001. While controlling for age and race, greater perceived economic hardship contributed to higher symptom distress (β = .36, p = .001, 95% CI: .34 to 1.34). Race, health care system distrust and social support did not significantly predict symptom distress. CONCLUSION: Assessment of perceived financial hardship prior to beginning chemotherapy is critical to identify those patients at risk for greater symptom distress.

To increase adherence with intensive care unit mobility by developing and implementing a mobility training program that addresses nursing barriers to early mobilisation.An intensive care unit mobility training program was developed, implemented and evaluated with a pre-test, immediate post-test and eight-week post-test. Patient mobility was tracked before and after training.A ten bed cardiac intensive care unit.The training program's efficacy was measured by comparing pre-test, immediate post-test and 8-week post-test scores. Patient mobilisation rates before and after training were compared. Protocol compliance was measured in the post training group.Nursing knowledge increased from pre-test to immediate post-test (p0.0001) and pre-test to 8-week post-test (p0.0001). Mean test scores decreased by seven points from immediate post-test (80±12) to 8-week post-test (73±14). Fear significantly decreased from pre-test to immediate post-test (p=0.03), but not from pre-test to 8-week post-test (p=0.06) or immediate post-test to 8-week post-test (p=0.46). Post training patient mobility rates increased although not significantly (p=0.07). Post training protocol compliance was 78%.The project successfully increased adherence with intensive care unit mobility and indicates that a training program could improve adoption of early mobility.

The addition of specialty palliative care to standard oncology care improves outcomes for patients with advanced cancer and their caregivers, but many lack access to specialty care services. Primary palliative care-meaning basic palliative care services provided by clinicians who are not palliative care specialists-is an alternative approach that has not been rigorously evaluated.A cluster randomized, controlled trial of the CONNECT (Care management by Oncology Nurses to address supportive care needs) intervention, an oncology nurse-led care management approach to providing primary palliative care for patients with advanced cancer and their family caregivers, is currently underway at 16 oncology practices in Western Pennsylvania. Existing oncology nurses are trained to provide symptom management and emotional support, engage patients and families in advance care planning, and coordinate appropriate care using evidence-based care management strategies. The trial will assess the impact of CONNECT versus standard oncology care on patient quality of life (primary outcome), symptom burden, and mood; caregiver burden and mood; and healthcare resource use.This trial addresses the need for more accessible models of palliative care by evaluating an intervention led by oncology nurses that can be widely disseminated in community oncology settings. The design confronts potential biases in palliative care research by randomizing at the practice level to avoid contamination, enrolling patients prior to informing them of group allocation, and conducting blinded outcome assessments. By collecting patient, caregiver, and healthcare utilization outcomes, the trial will enable understanding of the full range of a primary palliative care intervention's impact.

BACKGROUND Palliative care, integrated early, may reduce symptom burden in patients with idiopathic pulmonary fibrosis (IPF). However, limited information exists on timing and clinical practice. The purpose of this study was to describe the time course of events prior to death in patients with IPF managed at a specialty center with a focus on location of death and timing of referral for palliative care. METHODS Data were retrospectively extracted from the health system's data repository and obituary listings. The sample included all decedents, excluding lung transplant recipients, who had their first visit to the center between 2000 and 2012. RESULTS Median survival for 404 decedents was 3 years from diagnosis and 1 year from first center visit. Of 277 decedents whose location of death could be determined, > 50% died in the hospital (57%). Only 38 (13.7%) had a formal palliative care referral and the majority (71%) was referred within 1 month of their death. Decedents who died in the academic medical center ICU were significantly younger than those who died in a community hospital ward (P = .04) or hospice (P = .001). CONCLUSIONS The majority of patients with IPF died in a hospital setting and only a minority received a formal palliative care referral. Referral to palliative care occurred late in the disease. These findings indicate the need to study adequacy of end-of-life management in IPF and promote earlier discussion and referral to palliative care.

e13074Background: 5-10% of women with metastatic breast cancer (MBC) survive ≥5 years. Predictors of long-term survival are not clearly elucidated. We used data from 122 long-term MBC survivors (≥5...

Nurse practitioners working in family or primary care often need to incorporate specialty care knowledge into their practice. Knowledge of breast cancer staging, treatment, common side effects, and possible long-term sequelae is critically important for primary care nurse practitioners caring for women with a history of breast cancer. The unique considerations of breast cancer staging, treatment, and long-term effects are reviewed in this article. The importance of optimal communication between the cancer care provider and the primary care providers is highlighted.

Axon guidance at the Drosophila midline relies on dynamic regulation of the guidance receptor Robo by its negative regulator Comm. Recent findings demonstrate that Comm collaborates with the ubiquitin-protein ligase DNedd4 to inhibit Robo signaling by promoting the sorting of Robo into the endocytic pathway.