Mammography has a crucial role in the detection of breast cancer (Bc), yet it is not limitation-free. We hypothesized that the combination of mammography and cell-free DnA (cfDnA) levels may better discriminate patients with cancer. This prospective study included 259 participants suspected with Bc before biopsy. Blood samples were taken before biopsy and from some patients during and at the end of treatment. cfDNA blood levels were measured using our simple fluorescent assay. The primary outcome was the pathologic diagnosis of Bc, and the secondary aims were to correlate cfDnA to severity, response to treatments, and outcome. Median cfDnA blood levels were similar in patients with positive and negative biopsy: 577 vs. 564 ng/ml (p = 0.98). A significant decrease in cfDnA blood level was noted after the following treatments: surgery, surgery and radiation, neoadjuvant chemotherapy and surgery, and at the end of all treatments. to conclude, the cfDnA level could not be used in suspected patients to discriminate Bc. Reduction of tumor burden by surgery and chemotherapy is associated with reduction of cfDnA levels. in a minority of patients, an increase in post-treatment cfDnA blood level may indicate the presence of a residual tumor and higher risk. further outcome assessment for a longer period is suggested. Breast cancer (BC) is the most common form of cancer diagnosed in women worldwide, and is a leading cause of death among women in the United States and Israel 1. Mortality rates in developed countries have been declining in the last decade due to mammographic screening and improved adjuvant/neo-adjuvant therapy. Conversely, the mortality rate in undeveloped countries has been increasing due to the lack of screening and the westernization of reproductive and nutritional patterns 2. Mammography is the only screening tool proven effective for detecting early breast cancer and reducing mortality. Yet mammography and ultrasound-assisted core needle biopsy (US-CNB) limitations have been raised. In a meta-analysis of eight eligible trials of 600,000 women, Gøtzsche and Nielsen found no effect of screening on BC mortality after 10 years. These authors concluded that screening led to 30% over-diagnosis and over-treatment, or an absolute increase of 0.5% in the risk of death. In fact, nearly 20% of women without BC underwent biopsy after ten mammograms 3. As for US-CNB, the overall false-negative rate may reach 6.1% and a diagnosis underestimation rate of 31.4%. While US-CNB is useful in confirming invasive carcinomas, it has much lower efficacy when only ductal carcinoma in-situ (DCIS) is detected. Among lesions yielding DCIS at US-CNB, surgery revealed an infiltrating carcinoma in 16-55.5% of patients 4 .

That students reported increased empathy toward cancer patients despite increased trepidation about causing them suffering is promising. Such courses may be one way to counteract the decrease in empathy among students as they progress through medical school. As such, medical schools might consider including this type of curriculum in their preclinical oncology studies.

Immune checkpoint inhibitors, such as pembrolizumab, are transforming clinical oncology. Yet, insufficient overall response rate, and accelerated tumor growth rate in some patients, highlight the need for identifying potential responders. To construct a computational model, identifying response predictors, and enabling immunotherapy personalization. The combined dynamics of cellular immunity, pembrolizumab, and the melanoma cancer were modeled by a set of ordinary differential equations. The model relies on a scheme of T memory stem cells, progressively differentiating into effector CD8+ T cells, and additionally includes T cell exhaustion, reinvigoration and senescence. Clinical data of a pembrolizumab-treated patient with advanced melanoma (Patient O’) were used for model calibration and simulations. Virtual patient populations, varying in one parameter or more, were generated for retrieving clinical studies. Simulations captured the major features of Patient O’s disease, displaying a good fit to her clinical data. A temporary increase in tumor burden, as implied by the clinical data, was obtained only when assuming aberrant self-renewal rates. Variation in effector T cell cytotoxicity was sufficient for simulating dynamics that vary from rapid progression to complete cure, while variation in tumor immunogenicity has a delayed and limited effect on response. Simulations of a-specific clinical trial were in good agreement with the clinical results, demonstrating positive correlations between response to pembrolizumab and the ratio of reinvigoration to baseline tumor load. These results were obtained by assuming inter-patient variation in the toxicity of effector CD8+ T cells, and in their intrinsic division rate, as well as by assuming that the intrinsic division rate of cancer cells is correlated with the baseline tumor burden. In conclusion, hyperprogression can result from lower patient-specific effector cytotoxicity, a temporary increase in tumor load is unlikely to result from real tumor growth, and the ratio of reinvigoration to tumor load can predict personal response to pembrolizumab. Upon further validation, the model can serve for immunotherapy personalization.

Abstract. Molecular tools have increasingly been used for decision-making in patients with early breast cancer (EBC). Nevertheless, simple tools such as immunohistochemistry may still be required in particular cases to complement traditional and molecular prognosticators. In this study, the prognostic significance of three well-known immunohistochemical biomarkers, cathepsin D, E-cadherin and Ki67, was studied in 270 patients with EBC, followed by a median time of 126 months in a single institution. Histological examination was performed to confirm the histopathological diagnosis and select specimens. The specimens were evaluated using immunohistochemistry and survival curves were plotted. Results revealed the following patient characteristics: nodenegative/1-3 lymph nodes in 228 (86%) patients, hormone receptor-positive in 217 (80%); triple-negative in 31 (11%), and Her2-overexpression in 23 (9%) patients. Breast cancer-related events occurred in 37 patients (14%). A total of 217 patients (80%) survived. Receiver operating characteristic analysis for breast cancer-specific survival showed an area under curve for the clinicopathological model of 0.75 (95% CI, 0.79 (95% CI, for the three-biomarker model, and 0.82 (95% CI, 0.72-0.92) for the E-cadherin and cathepsin D only model. We propose that a simple prognostic model based on combined scores of E-cadherin and cathepsin D may aid treatment decisions in patients with EBC.