De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.     

The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer

Radium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC). Since then, the treatment landscape has changed dramatically with new hormonal agents (abiraterone and enzalutamide) considered to be the first-line choice for many patients. The optimal patient profile for radium-223 in the modern setting, and its best use either in sequence or in combination with other approved agents are unclear, with few definitive guidelines available. This article reports on the views of a group of urologists and medical oncologists experienced in treating patients with mCRPC with radium-223 in routine clinical practice. The aim is to provide an overview of the current use of radium-223 in the treatment of patients with mCRPC, and to discuss best practices for patient selection and on-treatment monitoring. Where agreement was reached, guidance on the optimal use of radium-223 is provided.     

Differential expression of microRNAs in Alzheimer's disease brain,blood, and cerebrospinal fluid

IntroductionSeveral microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.MethodsA systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.ResultsData from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10⁻⁴) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.DiscussionOur systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.     

Multifocal breast cancer and survival: Each focus does matter particularly for larger tumours

PurposeThe objective of this study is to determine whether the aggregate tumour size of every focus in multifocal breast cancer more accurately predicts 10-year survival than current staging systems which use the largest or dominant tumour size.Patients and methodsThis study examined the original histological reports of 848 consecutive patients with invasive breast cancer treated in New South Wales (NSW), Australia between 1 April 1995 and 30 September 1995. Multifocal tumours were assessed using two estimates of pathologic tumour size: largest tumour focus diameter and the aggregate diameter of every tumour focus. The 10-year survival of patients with multifocal tumours measured in both ways was compared to that with unifocal tumours.ResultsAt a median follow-up of 10.4 years, 27 of 94 patients (28.7%) with multifocal breast cancer have died of breast cancer compared to 141 of 754 (18.7%) with unifocal breast cancer (P = .022). Ten-year survival was not affected by size for tumours measuring 20 mm or less, whether or not dominant tumour size (87.9%) or aggregate tumour size (87.0%) was used for multifocal tumours, compared to unifocal tumours (88.1%). For tumours larger than 20 mm, 10-year survival was 72.1% for unifocal tumours compared to 54.7% (P = .008) for multifocal tumours using dominant tumour size, but this was 69.5% and not significant when multifocal tumours were classified using aggregate tumour size (P = .49). Multivariate analysis also confirmed the above-mentioned results after adjustment for important prognostic factors.ConclusionAggregate size of every focus should be considered along with other prognostic factors for metastasis when treatment is planned. The current convention of using the largest (dominant) lesion as a measure of stage and associated breast cancer survival needs further validation.