Evaluating the role of magnetic resonance imaging post-neoadjuvant therapy for breast cancer in the NEONAB trial.

BACKGROUND: Magnetic resonance imaging (MRI) accuracy after neoadjuvant systemic therapy (NST) for breast cancer varies according to hormone receptor (HR), human epidermal growth factor receptor type-2 (HER2) subtype and Ki-67 proliferation index. Whether MRI accuracy varies by genomic signatures is unknown. We examined the accuracy of MRI in the NEONAB trial (Clinicaltrials.gov #: NCT01830244). AIM: To examine the accuracy of MRI to predict pathological response to neoadjuvant therapy for breast cancer in the NEONAB trial. METHODS: Patients with stages II-III breast cancer received sequential epirubicin, cyclophosphamide and nab-paclitaxel and trastuzumab if they were HER2+. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess the utility of preoperative MRI to predict pathological complete response (pCR). Bland-Altman plots were used to assess agreement between MRI and pathological assessment of residual disease. RESULTS: MRI correctly predicted pCR in 64.1% of the cohort. Sensitivity and specificity were 52% and 78%, respectively; PPV 73% and NPV 58%. MRI predicted pCR most accurately in HER2-positive patients; sensitivity 58%, specificity 100%, PPV 100% and NPV 38%. MRI had higher PPV and NPV in tumours with Ki-67 ≥ 15% than tumours with Ki-67 < 15%, 75% versus 50% and 57.5% versus 50%, respectively. In this study, MRI underestimated residual tumour size by 1.65 mm (limits of agreement: 43.07-39.77 mm). CONCLUSIONS: MRI appears more accurate for predicting pCR in HER2+ disease than other subtypes and in cancers with Ki-67 ≥ 15% compared to those with Ki-67 < 15%. Accuracy of MRI in our HR+, RS ≥ 25 cohort is comparable to previous reports of unselected HR+ disease. MRI post-NST should be interpreted in conjunction with HER2 status and Ki-67 index of the primary.

Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial-Clinical outcomes and molecular determinants of response.

BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses. RESULTS: The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones. CONCLUSIONS: This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT01830244.

Rolling away the stone: post-abortion women in the Christian community.

This article seeks to bring to awareness and address the issues of a neglected group of people in need of pastoral care: women who have had an abortion. It offers some commentary regarding what many women experience following an abortion, focuses on the story of a specific woman, and goes on to offer a biblical perspective for a pastoral response to their needs. Responses to the article are offered by a healthcare chaplain and a seminary professor.

Cost effectiveness of community-based physical activity interventions.

BACKGROUND: Physical inactivity is associated with the increased risk of many chronic diseases. Such risks decrease with increases in physical activity. This study assessed the cost-effectiveness of population-wide strategies to promote physical activity in adults and followed disease incidence over a lifetime. METHODS: A lifetime cost-effectiveness analysis from a societal perspective was conducted to estimate the costs, health gains, and cost-effectiveness (dollars per quality-adjusted life year [QALY] gained, relative to no intervention) of seven public health interventions to promote physical activity in a simulated cohort of healthy U.S. adults stratified by age, gender, and physical activity level. Interventions exemplifying each of four strategies strongly recommended by the Task Force on Community Preventive Services were evaluated: community-wide campaigns, individually adapted health behavior change, community social-support interventions, and the creation of or enhanced access to physical activity information and opportunities. Each intervention was compared to a no-intervention alternative. A systematic review of disease burden by physical activity status was used to assess the relative risk of five diseases (coronary heart disease, ischemic stroke, type 2 diabetes, breast cancer, and colorectal cancer) across a spectrum of physical activity levels. Other data were obtained from clinical trials, population-based surveys, and other published literature. RESULTS: Cost-effectiveness ratios ranged between $14,000 and $69,000 per QALY gained, relative to no intervention. Results were sensitive to intervention-related costs and effect size. CONCLUSIONS: All of the evaluated physical activity interventions appeared to reduce disease incidence, to be cost-effective, and--compared with other well-accepted preventive strategies--to offer good value for money. The results support using any of the seven evaluated interventions as part of public health efforts to promote physical activity.

Recruitment of older women: lessons learned from the Baltimore Hip Studies.

OBJECTIVES: This study used a qualitative approach in which participants were asked to write about their experiences in recruiting older women into either one of two exercise intervention studies that are part of the Baltimore Hip Studies. The sample included 8 researcher nurses all women, White, and 42-53 years of age. BACKGROUND: Older adults, particularly older women, are less likely to participate in research studies when compared to their younger counterparts. The purpose of this study was to explore the techniques successfully used by research nurses in the Baltimore Hip Studies to recruit older women after hip fracture into exercise intervention studies. METHOD: Data analysis was performed using basic content analysis (Crabtree & Miller, 1992; Miles & Huberman, 1984) "in vivo" coding (Dowd, 1991), or "grounded" coding (Glaser & Strauss, 1967), which involves using the informants' own words to capture a particular idea. RESULTS: A total of 16 codes were identified and reduced to nine themes. Seven themes focused on techniques that facilitated recruitment: (a) caring for individuals; (b) emphasizing benefits; (c) eliciting support from others; (d) being an expert; (e) using role models; (f) using good timing; and (g) giving good first impressions. The remaining two themes identified barriers to recruitment: (a) time commitment and (b) lack of support. DISCUSSION: Based on these themes, specific recruitment techniques are recommended. Ongoing research, however, is needed to establish the most effective recruitment procedures with older women.