Neoadjuvant Therapy and Axillary Lymph Node Status in HER2-Positive Breast Cancer.

Based on an estimating model, the aim of our study was to evaluate the axillary lymph node involvement of patients with primary invasive early human epidermal growth factor receptor 2 (HER2)-positive breast cancer before receiving neoadjuvant therapy (NAT). Patients with primary surgery (n = 63) were compared with patients who had received NAT (combined chemo/HER2-targeted antibody therapy) before surgery (n = 152). In patients receiving NAT, a positive N stage was estimated in 73.2 (49.8%) tumors resulting in a conversion (positive N stage-ypNpositive) of 35.5%. In 126 cases with ypN0 stage, a positive N stage was estimated in 41.4%.

Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria.

BACKGROUND: Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register. METHODS: Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824. RESULTS: A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC. CONCLUSION: The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.

Use of polysaccharide hemostatic agent (HaemoCer™) in breast cancer surgery to reduce postoperative complications: A randomised controlled trial.

Postoperative wound-site bleeding, tissue inflammation and seroma formation are well-known complications in the field of breast surgery. Hemostatic agents consisting of polysaccharides may be used intra-operatively to minimise postoperative complications. We conducted a prospective randomised-controlled, single-centre study including 136 patients undergoing breast-conserving surgery for invasive or intraductal breast cancer. Of these, 68 patients were randomised to receive an absorbable polysaccharide hemostatic agent into the wound site during surgery, while 68 patients were randomised to the control group and did not receive any hemostatic agent. Primary outcome was the total volume of postoperative drained fluid from the surgical site. Secondary outcomes were the number of days until drain removal and rate of immediate postoperative surgical site infection Patients in the intervention group had significantly higher drainage output volumes compared with the control group 85 mL (IQR 46.25-110) versus 50 mL (IQR 30-75), respectively; (P = .003). Univariable linear regression analyses showed a significant association between the surgical specimen and the primary outcome (P < .001). After multivariable analysis, the use of absorbable polysaccharide hemostatic product was no longer significantly associated with a higher drainage output and only the size of the surgical specimen remained a significant predictor. The number of days until drainage removal and the postoperative seroma formation were higher in the intervention group (P = .004) and (P = .003), respectively. In our study, intraoperative application of polysaccharide hemostatic agent during breast-conserving surgery did not decrease postoperative fluid production. Only the size of the surgical specimen was significantly associated with postoperative drainage volume.

Extraosseous osteoblastoma: A rare cause of breast mass in a prepubertal girl.

Extraosseous osteoblastoma of the breast, a rare disease, was diagnosed in a prepubertal girl. After tumor excision, the patient recovered well and an optimal cosmetic result was achieved. Interdisciplinary discussions about the case are essential.

Invasive lobular carcinoma: clinicopathological features and subtypes.

OBJECTIVE: To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. METHODS: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). RESULTS: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (+), have a lower proliferation rate (Ki67 <14%), and a higher pathological T stage (pT2-4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ER+, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1-3) was significantly more frequent with ILC versus IDC. CONCLUSIONS: Our data suggest that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

"Anemia and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients".

We analyzed the effect of anemia on tumor response of patients with primary invasive breast cancer (BC) receiving neoadjuvant chemotherapy (NACT). The patient collective was very homogenous; finally, 74 BC patients with identical medication and duration of NACT were enrolled. After completion of NACT, 49 patients (66.2%) had a post-NACT Hb level <12 g/dl. In the anemic group, we found a tendency of lower median tumor response compared to nonanemic patients at this time (15 versus 17 mm, retrospectively, p = 0.18). Age at diagnosis significantly correlated with the difference of Hb [before initiation - after completion of NACT] (correlation coefficient = 0.40, p < 0.001).

Signet Ring Cell Carcinoma of the Lung: A Diagnostic Pitfall in Pregnancy.

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22nd week of gestation.

Association of Cytokeratin 5 and Claudin 3 expression with BRCA1 and BRCA2 germline mutations in women with early breast cancer.

BACKGROUND: It is important to identify biomarkers associated with BRCA mutation in women with early breast cancer (BC) to improve early identification of mutation carriers. Thus, in this study, we examined the protein expression of claudin (CLDN) 3, CLDN4, CLDN7, and E-cadherin. Moreover, we analyzed additional histopathological variables and their associations in familial BC. METHODS: Immunohistochemical analysis for CLDNs and E-cadherin was performed on 237 BC cases of three different subsets of BC tumors: 62 from BRCA1 mutation carriers, 59 from BRCA2 mutation carriers, and 116 tumors from patients with BRCA wild type (WT) as controls. Histopathological data were also analyzed in the different subgroups. Logistic regression and receiver operation characteristic (ROC) curve were conducted to investigate factors associated with BRCA tumors. RESULTS: Expression of CLDN3 positively correlated with BRCA-mutated BC. CLDN3 was expressed in 58% of BRCA1-mutated tumors compared to only 7% in BRCA2-mutated tumors (p < 0.001) and 1% in WT tumors (p < 0.001). CK5 and CK14 expression were also more likely to arise in BRCA1 tumors (44 and 16%, respectively) than in the control group (8 and 4%) (p < 0.001, p = 0.012, respectively). We also found a significantly higher proportion of CK5+ among BRCA1 tumors (44%) in comparison with BRCA2-related BC (8%) (p < 0.001). In addition, there was a significant difference between both groups regarding CK14: positive expression in 16 and 5%, respectively (p = 0.030). CK5 and CK14 did not differ between the BRCA2 group and the WT tumors significantly. In a multivariate regression model, expression of CK5 (Odds ratio (OR): 6.46; 95% confidence interval (CI): 1.52-27.43; p = 0.011), and CLDN3 (OR: 200.48; 95% CI: 21.52-1867.61; p < 0.001) were associated with BRCA1 mutation status. CONCLUSIONS: Our data suggests that CLDN3, CK5, and CK14 in combination with ER, PR and HER2 are associated with BRCA1 mutation status.

Differential Claudin 3 and EGFR Expression Predicts BRCA1 Mutation in Triple-Negative Breast Cancer.

BRCA-1 mutation-associated triple-negative breast cancer (TNBC) has been hypothesized to exhibit a phenotype that is distinct from non-mutation carriers. We have analyzed immunohistochemically detected cytokeratins 5 and 14, epidermal growth factor receptor (EGFR), claudin (CLDN) 3, 4, and 7, and E-cadherin in 57 TNBC (32 BRCA1 and 8 BRCA2 tumors, 17 WT tumors). Positive staining of CLDN3 and negative EGFR expression in TNBC are associated with a BRCA1 mutation. EGFR and CLDN3 expression was able to predict the presence of BRCA1 mutation (area under curve 0.802, p < 0.001). This could help in guiding the decision for BRCA testing.

Efficient leukocyte depletion by a novel microfluidic platform enables the molecular detection and characterization of circulating tumor cells.

RT-qPCR is a highly sensitive approach to detect rare transcripts, as derived from circulating tumor cells (CTCs) in the blood of cancer patients. However, the presence of unwanted leukocytes often leads to false positive results. Here, we evaluated whether the micro-fluidic Parsortix™ technology is appropriate to remove these leukocytes and thereby finally to improve the overall approach. In this study, we established a workflow including the micro-fluidic Parsortix™ technology for the molecular detection of CTC related transcripts. Background levels of EpCAM, PPIC, TUSC3, and MAL2 were efficiently removed due to an up to 106-fold depletion of leukocytes. The presence of these gene markers was observed in Parsortix™-enriched blood samples from patients with primary and recurrent gynecological cancer (32% and 14%), as well as in 86% of the metastatic breast cancer samples, at a very high specificity. In the ovarian cancer samples, PPIC was the most prominent gene marker, contributing to all positive cases and at least to 70% of the positive cases after pre-amplification of the respective target genes. Expanding the analytical panel up to 29 gene markers further increased the positivity rate (primary gynecological cancer: 95%, recurrent gynecological cancer: 100%, metastatic breast cancer: 92%). The established workflow strongly improved the overall molecular analysis of the target cells by the efficient removal of contaminating cells, and, thereby offers great promise for the molecular characterization of CTCs.

[Biomarkers - the way towards individualized chemotherapy in non-small cell lung cancer (NSCLC)]. / Biomarker - der Weg zur individualisierten Chemotherapie beim nicht-kleinzelligen Bronchialkarzinom.

Tumor biology is increasingly important when choosing the optimal therapy for patients with non-small cell lung cancer (NSCLC). A number of potential biomarkers is under investigation in the hope that it will be possible to identify markers that assist in the selection of patients for specific therapies in the future. Patients with an elevated DNA repair capacity, indicated by an increased tumoral expression of excision repair cross complementation group-1 (ERCC1) or ribonucleotid reductase subunit M1 (RRM1) may benefit less from cisplatin-based and gemcitabine-based chemotherapy, respectively. Overexpression of the cell cycle regulator p27 affects response to various anticancer drugs and increased levels of class III beta-Tubulin are associated with taxane resistance. Promising results so far suggest that customized therapy for individual patients with the help of predictive biomarkers is possible and it is likely that this strategy will improve treatment of NSCLC in the future.