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Membrane nanotubes are cytosolic protrusions with diameters

Digital PCR is a highly accurate method of determining DNA concentration. We adapted digital PCR to determine the presence of oncogenic amplification through noninvasive analysis of circulating free plasma DNA and exemplify this approach by developing a plasma DNA digital PCR assay for HER2 copy number. The reference gene for copy number assessment was assessed experimentally and bioinformatically. Chromosome 17 pericentromeric probes were shown to be suboptimal, and EFTUD2 at chromosome position 17q21.31 was selected for analysis. Digital PCR assay parameters were determined on plasma samples from a development cohort of 65 patients and assessed in an independent validation cohort of plasma samples from 58 patients with metastatic breast cancer. The sequential probability ratio test was used to assign the plasma DNA digital PCR test as being HER2-positive or -negative in the validation cohort. In the development cohort, the HER2:EFTUD2 plasma DNA copy number ratio had a receiver operator area under the curve (AUC) = 0.92 [95% confidence interval (CI), 0.86-0.99, P = 0.0003]. In the independent validation cohort, 64% (7 of 11) of patients with HER2-amplified cancers were classified as plasma digital PCR HER2-positive and 94% (44 of 47) of patients with HER2-nonamplified cancers were classified as digital PCR HER2-negative, with a positive and negative predictive value of 70% and 92%, respectively. Analysis of plasma DNA with digital PCR has the potential to screen for the acquisition of HER2 amplification in metastatic breast cancer. This approach could potentially be adapted to the analysis of any locus amplified in cancer.

Modern neoadjuvant systemic therapy (NST) can result in high pathologic complete response rates (pCR) in triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) breast cancer. The role of surgery is, therefore, being reconsidered in this rapidly evolving field. This report presents oncological outcomes of seven patients with TN or HER2+ breast cancer, with exceptional response to NST, and a post-NST image-guided vacuum assisted biopsy showing no residual disease (ypT0), who opted not to have breast surgery. The median age was 49 (IQR 36–61) years and the median tumour size at diagnosis was 50 (IQR 16–65) mm. All patients received breast radiotherapy and continued adjuvant systemic therapies as appropriate. At a median follow-up of 67 (IQR 61–77) months, all patients were alive and free of disease. This small case series supports the need for further research in 'exceptional responders' to provide safe, individualized patient-centred care. [ABSTRACT FROM AUTHOR]

Purpose Leptomeningeal disease (LMD) is an uncommon complication of advanced breast cancer. The prognosis is poor, and although radiotherapy (RT), systemic and intra-thecal (IT) chemotherapy are accepted treatment modalities, efficacy data are limited. This study was designed to evaluate potential predictors of survival in this patient group. Methods Breast cancer patients with LMD diagnosed by MRI in a 10-year period (2004–2014) were identified from electronic patient records. PFS and OS estimates were calculated using Kaplan-Meier method, with planned sub-group analysis by treatment modality. Cox regression was employed to identify significant prognostic variables. Results We identified 182 eligible patients; all female, median age at LMD diagnosis 52.5 years (range 23–80). Ninety patients (49.5%) were ER positive/HER2 negative; 48 (26.4%) were HER2 positive, and 27 (14.8%) were triple negative. HER2 status was unknown in 17 (9.3%). Initial management of LMD was most commonly whole or partial brain RT in 62 (34.1%), systemic therapy in 45 (24.7%) or supportive care alone in 37 (20.3%). Fourteen patients (7.7%) underwent IT chemotherapy, of whom two also received IT trastuzumab. From diagnosis of LMD, the median PFS was 3.9 months (95%CI 3.2–5.0) and median OS was 5.4 months (95%CI 4.2–6.6). Patients treated with systemic therapy had the longest OS (median 8.8 months, 95%CI 5.5–11.1), compared to RT; 6.1 months (95%CI 4.2–7.9 months), IT therapy; 2.9 months (95%CI 1.2–5.8) and supportive care; 1.7 months (95%CI 0.9–3.0). On multivariable analysis, triple negative histology, concomitant brain metastases, and LMD involving both the brain and spinal cord were associated with poor OS. Conclusions Breast cancer patients with triple negative LMD, concomitant brain metastases or LMD affecting both the spine and brain have the poorest prognosis. Clinical trials to identify more effective treatments for these patients are urgently needed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Locoregional recurrence occurs in a significant number of patients with breast cancer. This can result in substantial morbidity and mortality. Chest wall resection is well-documented for palliation and local control in chest wall relapse; an extension of this surgery is parasternal or sternal resection. Methods: A retrospective review of medical records of eighteen women who underwent sternal or parasternal resection with curative intent between 1998 and 2007 was undertaken. Results: 12 patients had total sternal resection, five patients had sub-total sternal resection and one patient had resection of tumour and ribs. 17 patients required the insertion of a composite Marlex® methyl-methacrylate chest wall prosthesis, followed by soft tissue reconstruction with a pectoralis major or latissimus dorsi flap, in the majority of cases. In-hospital and 30-day mortality was 0%. One and two-year overall survival was 87% and 80% respectively. The median recurrence-free survival was 18 months (95% CI 4–31 months). There was local and distant recurrence in one patient (5%), local recurrence in two patients (11%) and distant recurrence in eight patients (44%), with 15 out of 18 patients (77%) remaining free from local recurrence at 5 years. Conclusions: En bloc sternal resection for parasternal recurrence in breast cancer involves extensive surgery but in our experience can be performed with very low mortality and morbidity. In selected patients it provides good long term local control, relief of pain and improved cosmesis. [ABSTRACT FROM AUTHOR]

Summary: Patients with metastatic breast cancer (MBC) are increasingly offered third line chemotherapy. We have reviewed the response rate (RR), time to progression (TTP) and survival of 149 patients in this setting and have investigated factors that influence their outcome. The RR, TTP and survival were 30%, 4 and 8 months, respectively, and should serve as a benchmark for future studies. Response to previous chemotherapy was the only independent variable predicting RR, TTP and survival, p=0.025, 0.04 and 0.004, respectively. Thirty-two percent of patients did not respond to the first two lines of chemotherapy and had a lower RR and a significantly shorter TTP and survival. In conclusion, third line chemotherapy for MBC is sometimes effective in patients who have responded to previous chemotherapy. Patients who do not respond to the first two lines of chemotherapy should be considered for clinical trials or supportive care. [Copyright &y& Elsevier]

Abstract: The most recent Oxford Overview analysis shows that tamoxifen remains a highly effective adjuvant endocrine therapy with continuing benefit for at least 15 years. The aromatase inhibitors (AIs) achieve a further small reduction in recurrence in postmenopausal women either as first-line treatment or sequentially after 2–3 years tamoxifen but so far usually without survival benefit. Differences in side effects are minor and specifically there is no evidence for significant differences in cardiovascular side effects. Extended adjuvant therapy with an AI after 5 years tamoxifen gives important additional protection to women with higher risk cancers. The relative benefits of first-line vs. sequential AIs after 2–3 years tamoxifen await the outcome of current trials. The major outstanding questions include duration of endocrine therapy, the value of ovarian suppression in premenopausal women in addition to other treatments, and the selection of patients who require endocrine therapy alone without additional chemotherapy. [Copyright &y& Elsevier]

Abstract: Major advances in all aspects of breast cancer research have been made over the past year, ranging from cancer prevention to the management of patients with advanced disease. Important advances have been reported in the prevention of breast cancer, the identification of risk factors, and in screening methodology. Furthermore, advances have been reported in the discovery and validation of prognostic and predictive molecular markers. Inroads have been made in the identification of active and safe combination regimes for advanced disease both using traditional cytotoxic chemotherapy and the newer targeted drugs trastuzumab and bevacizumab, and in determining the role of adjuvant radiotherapy in elderly patients with hormone sensitive tumours. Key data have also been presented on the role of aromatase inhibitors as endocrine therapy in the management of postmenopausal patients, in addition to seminal data highlighting the role of trastuzumab in the adjuvant setting. In this article, we report key studies presented at major international meetings and in top peer-reviewed journals over the past year. We present this data in context and discuss its current and potential impact. [Copyright &y& Elsevier]

Almost 50% of breast cancer occurs in women over the age of 65 years. The incidence of non standard adjuvant treatment increases with age and this group are under represented in clinical trials. We discuss tools to aid patient selection and adjuvant treatments including surgery, radiotherapy and systemic therapies for this group of patients. [ABSTRACT FROM AUTHOR]

Abstract: It is widely believed by both doctors and patients that regular follow-up with imaging is important for patients who have been treated for early breast cancer. In reality, current evidence does not support this. Randomised trials have shown no benefit for intensive versus routine follow-up and studies have also shown that follow-up by a general practitioner or nurse specialist is likely to be as effective as by a breast cancer specialist. Specifically there is no evidence that specialised imaging including PET/CT is of any benefit. Newer approaches including the assessment of circulating tumour cells and/or circulating tumour DNA may eventually prove advantageous, but currently must be considered experimental. In summary, current evidence suggests that there is no basis for intensive follow-up beyond standard regular clinical assessment and annual mammography following treatment of early breast cancer. There may be better models for follow-up than the traditional resource-intensive hospital outpatient visit, including nurse-led open access follow-up. Monitoring for long-term sequelae of treatment is becoming as important as the detection of recurrence in an era where long-term survival is increasingly common. [Copyright &y& Elsevier]