Simultaneous Integrated Boost in Once-weekly Hypofractionated Radiotherapy for Breast Cancer in the Elderly: Preliminary Evidence

Aim: To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility. Patients and Methods: Fifty patients were treated with a hypofractionated regimen: 28.5\ub12.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases. Inclusion criteria: patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group. Results: The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%). Conclusion: Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly

Her2 assessment using quantitative reverse transcriptase polymerase chain reaction reliably identifies Her2 overexpression without amplification in breast cancer cases

Background: Immunohistochemistry (IHC) and fluorescent-in situ hybridization (FISH) are standard methods to assess human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients. Real-time quantitative polymerase-chain-reaction (qRT-PCR) is able to detect HER2 overexpression. Here we compared FISH, IHC, quantitative PCR (qPCR), and qRT-PCR to determine the concordance rates and evaluate their relative roles in HER2 determination. Patients and methods: We determined HER2 status in 153 BC patients, using IHC, FISH, Q-PCR and qRT-PCR. In discordant cases, we directly measured HER2 protein levels using Western blotting. Results: The overall agreement (OA) between FISH and Q-PCR was 94.1, with a k value of 0.87. Assuming FISH as the standard reference, Q-PCR showed an 86.1% sensitivity and a 99.0% specificity with a global accuracy of 91.6%. OA between FISH and qRT-PCR was 90.8% with a k value of 0.81. Of interest, the disagreement between FISH and qRT-PCR was mostly restricted to equivocal cases. HER2 protein analysis suggested that qRT-PCR correlates better than FISH with HER2 protein levels, particularly where FISH fails to provide conclusive results. Significance: qRT-PCR may outperform FISH in identifying patients overexpressing HER2 protein. Q-PCR cannot be used for HER2 status assessment, due to its suboptimal level of agreement with FISH. Both FISH and Q-PCR may be less accurate than qRT-PCR as surrogates of HER2 protein determination

No Ink on Ductal Carcinoma in Situ: A Single Centre Experience

Abstract Introduction: The incidence of ductal carcinoma in situ (DCIS) of the breast has greatly increased thanks to the widespread use of screening mammography. The primary aim of surgery is to prevent local recurrence by achieving a clear margin of resection although its extent still represents a controversial issue. Hence, a retrospective analysis of patients undergoing surgery for DCIS was performed in order to assess the association of margin widths of < 1 mm, 1 to 2 mm, and > 2 mm with ipsilateral breast tumor recurrence (IBTR) considering also the potential role of host-, tumor- and treatment-related factors. Methods: From 2000 to 2016, 388 patients diagnosed with pure DICS undergoing BCS with or without post-operative RT at the Breast Unit of \u201cOspedale Policlinico San Martino\u201d in Genoa were selected. The pathologic analysis was always performed according to a standardized protocol including the measure of the microscopic distance to the nearest radial margin: positive margins were those with DCIS present at the inked margin; close margins were considered to have tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were > 2 mm. Results: At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). In univariate analysis there was a significant difference in IBTR by comparing positive versus close/negative margins of excision (P = 0.05) and the number of re-operations (P = 0.000). On multivariate analysis, both the margin status (P = 0.002) and the number of re-operations (P < 0.001) were still significantly associated with IBTR. The actuarial IBTR rates were significantly different in patients with a positive margin of excision at the primary operation as compared to patients with close/negative margins (log-rank test, P = 0,042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; > 2 mm) was not significant (log-rank test, P = 0,243). Conclusions: The policy of \u201cno ink on the tumor\u201d that is well accepted for invasive breast cancer can be translated to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive margin of excision as compared to patients with close/negative margins

A Case of Extra-Abdominal Fibromatosis.

Extra-abdominal fibromatosis is a rare benign disease, characterized by a local but not metastatic invasivity. It occurs more often in females and it has a higher incidence between puberty and the 4th decade of life

Moving trastuzumab emtansine (T-DM1) to the early setting of breast cancer treatment

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Assessment of Circulating Nucleic Acids in Cancer: From Current Status to Future Perspectives and Potential Clinical Applications

Current approaches for cancer detection and characterization are based on radiological procedures coupled with tissue biopsies, despite relevant limitations in terms of overall accuracy and feasibility, including relevant patients’ discomfort. Liquid biopsies enable the minimally invasive collection and analysis of circulating biomarkers released from cancer cells and stroma, representing therefore a promising candidate for the substitution or integration in the current standard of care. Despite the potential, the current clinical applications of liquid biopsies are limited to a few specific purposes. The lack of standardized procedures for the pre-analytical management of body fluids samples and the detection of circulating biomarkers is one of the main factors impacting the effective advancement in the applicability of liquid biopsies to clinical practice. The aim of this work, besides depicting current methods for samples collection, storage, quality check and biomarker extraction, is to review the current techniques aimed at analyzing one of the main circulating biomarkers assessed through liquid biopsy, namely cell-free nucleic acids, with particular regard to circulating tumor DNA (ctDNA). ctDNA current and potential applications are reviewed as well

Surgical approach in the Management of IBD.

Crohn\u2019s disease (CD)and Ulcerative colitis (UC) are inflammatory bowel disease (IBD) with a chronic course and a strong impact on the patient\u2019s condition, leading to a reduced quality of life

Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer

PURPOSE: Breast cancer (BC) is a heterogeneous disorder, with variable response to systemic chemotherapy. Likewise, BC shows highly complex immune activation patterns, only in part reflecting classical histopathological subtyping. Schlafen-11 (SLFN11) is a nuclear protein we independently described as causal factor of sensitivity to DNA damaging agents (DDA) in cancer cell line models. SLFN11 has been reported as a predictive biomarker for DDA and PARP inhibitors in human neoplasms. SLFN11 has been implicated in several immune processes such as thymocyte maturation and antiviral response through the activation of interferon signaling pathway, suggesting its potential relevance as a link between immunity and cancer. In the present work, we investigated the transcriptional landscape of SLFN11, its potential prognostic value, and the clinico-pathological associations with its variability in BC. METHODS: We assessed SLFN11 determinants in a gene expression meta-set of 5061 breast cancer patients annotated with clinical data and multigene signatures. RESULTS: We found that 537 transcripts are highly correlated with SLFN11, identifying "immune response", "lymphocyte activation", and "T cell activation" as top Gene Ontology processes. We established a strong association of SLFN11 with stromal signatures of basal-like phenotype and response to chemotherapy in estrogen receptor negative (ER-) BC. We identified a distinct subgroup of patients, characterized by high SLFN11 levels, ER- status, basal-like phenotype, immune activation, and younger age. Finally, we observed an independent positive predictive role for SLFN11 in BC. CONCLUSIONS: Our findings are suggestive of a relevant role for SLFN11 in BC and its immune and molecular variability.status: publishe

No Axillary Lymph Node Dissection in Breast Cancer Patients with Sentinel Lymph Node Micrometastasis

Follow-up data of a series of 75 breast cancer patients with sentinel node (SN) micrometastases only (between 0.2 and 2 mm) and favorable histopathological features of the primary tumor (well-differentiated, T1 tumors without lymphovascular invasion) who refused completion axillary lymph node dissection (ALND) or who were unsuitable for surgery were assessed in order to detect the rate of axillary recurrence after an adjuvant chemoand/or hormonal adjuvant treatment was given. The great majority of patients (81.3%) did not undergo ALND due to the existence of favorable histopathologic factors while the rest were equally distributed among over 75-year-old women (10.6%) and patients at a high surgical risk due to comorbid conditions (9.3%). Sixty-six patients (88%) underwent conservative treatment (lumpectomy followed by adjuvant breast radiotherapy) while the remaining nine patients (12%) had total mastectomy; 72 out of 75 patients (96%) received some forms of adjuvant chemo- and/or hormone-therapy. After a median follow-up of 38 months (range 12 - 84 months), nine out of 75 patients (12%) had a disease relapse, only one of them (1.3%) being affected by an axillary recurrence in the untreated axilla three years after primary surgery. On these grounds, completion ALND could be safely omitted in patients with SN micrometastasis and favorable histopathological characteristics of the primary neoplasm due to the very low rate of axillary recurrence with no detrimental effect on survival

Axillary ultrasound and Fine-Needle Aspiration Cytology in the preoperative staging of axillary node metastasis in breast cancer patients

Objective A prospective observational clinical study was undertaken to assess the accuracy of preoperative Axillary Ultrasound (AUS) plus Fine-Needle Aspiration Cytology (FNAC) as well as and its clinical utility, that is the capacity of the information supplied by the test to guide the clinical decision-making. Materials and methods from January 2013 to August 2015, 400 female patients with pT1-3 cN0 operable breast cancer underwent AUS with FNAC at the Breast Unit of the \u201cIRCCS San Martino-IST\u201d in Genoa (Italy). Results 127 out of 400 patients (31.7%) had axillary lymph node metastases; in 69 out of 127 node-positive patients (54.3%) AUS detected at least one abnormal lymph node, and in 56 out of 127 patients (44.1%) the abnormal sonographic pattern of the lymph node was coupled with a positive FNAC finding. No false-positive finding by both AUS-alone or combined AUS/FNAC was observed. AUS-alone had sensitivity of 54.3% (69/127), specificity of 100% (273/273), PPV of 100% (69/69), NPV of 82.5% (273/331), and accuracy of 85.5% (342/400). Combined AUS/FNAC had sensitivity of 44.1% (56/127), specificity of 100% (273/273), PPV of 100% (56/56), NPV of 79.4% (273/344), and accuracy of 82.2% (329/400). Conclusions AUS-alone or combined AUS/FNAC had a high accuracy rate coupled with a more than satisfactory efficiency due to their low costs and easy access for the preoperative staging of the axilla. Notably, AUS-alone might be suggested for the preoperative staging of patients with early stage breast cancer because FNAC did not increased the specificity but reduced the sensitivity of the technique. Patients with negative findings might undergo either SLNB or close observation while waiting for the definitive results of ongoing SOUND randomized clinical trial