Abstract: Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme- linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.
Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population.
E18144 Background: In 2012 the American Society for Clinical Oncology identified five key opportunities in Oncology to improve patient care recommending against imaging tests for staging in patients with early breast cancer (EBC) at low risk for metastases. Similarly the European Society of Medical Oncology guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcome of staging investigations (SI) in aEBC at our institution. Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SI were recorded. Data were analyzed to determine associations between the use of SI and clinical characteristics (chi-square tests, independent samples t-tests and Mann-Whitney U). Results: We identified 295 eligible aEBC patients. Mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Pathology: T1 48%; N0 73%; grade 3 – 33%; ER+ 84%, HER2+ 13%, triple negative 12%. Adjuvant therapy: chemotherapy 36%, Trastuzumab 10%, endocrine therapy 76%, radiotherapy 79%. 168 patients (57%) had 332 SI: chest x-ray 4%; abdominal ultrasound 4%; bone scan 53%; CT scan 52%. Overt metastatic disease was found in 1 bone scan and 4 CT scans. 71 patients (24%) underwent 138 follow-up imaging tests none of which were diagnostic for metastases. Of 9 biopsies 4 were malignant (1 metastatic and 3 new primaries). Factors significantly associated with staging: younger age (p 0.001), premenopausal status (p 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001) and triple negative status (p 0.007), use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3 year period at our institution more than 50% of aEBC patients underwent a total of 470 imaging tests and 9 biopsies with low diagnostic value, supporting current guidelines that recommend against routine use of SI in this population.
Abstract: 2011 was a landmark year in the therapy for metastatic melanoma as it was the year that both Ipilmumab and Vemurafenib were approved by the FDA. Preceding this lay many years of frustration with no improvement in survival rates for 40 years. The prior standard therapy consisted of two main options, dacarbazine a non classic alkylating agent approved in the 1970s on the basis of overall response rates but having no benefit on survival and high dose IL2, approved in 1998 on the basis of durable complete response in a minority of patients. Thus the survival rates of patients with metastatic melanoma had remained largely unchanged since the 1970s with a median overall survival of 6 to 9 months. Metastatic melanoma is responsible for more than 75% of deaths from all forms of skin cancer, yet only represents less than 5% of all skin cancer diagnosis [1]. It is the most aggressive form of skin cancer and it is estimated that 76, 250 patients will be diagnosed in the United States in 2012 with 9,180 deaths [2]. The fruition of immunological and molecular research Ipilimumab, a CTLA4 antibody and Vemurafenib, a BRAF inhibitor in patients with BRAF mutation, have shown significant improvements in overall survival. With more targeted therapy options on the horizon these are significant times of hope for a disease which has proved so elusive in the past and has grown dramatically in incidence and annual mortality during the last few decades [3, 4]. This review will describe these new advances in targeted molecular and immunological therapies on the background of older therapies and also look at potential future therapy targets.