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Introduction: The cavity shaving (CS) technique was described in breast conserving surgery to reduce the rate of reoperation avoiding the need for intraoperative margin analysis. This study assesses differences in the rates of involvement of the surgical margin (requiring further surgery) and volume of surgical specimens, depending on the use or not of this technique., Material and Methods: A retrospective cohort study was conducted in patients with breast carcinoma who underwent breast conserving surgery between 2013 and 2019. They were divided into two groups depending on whether the cavity shaving technique was used or not. Primary outcomes of the study included presence of final margin involvement, requiring need for further surgery, and the volume of excised tissue comparing the study groups., Results: A total of 202 cases were included: 92 in the control group and 110 in the cavity shaving group. Significant differences were found regarding involvement of the final margin (19.57% control group vs. 4.55% cavity shaving group; p = 0.010). The volume of additional surgical specimens were significantly greater in the traditional technique group than in the shaving technique (46.43 vs 13.32 cm 3 ; p = 0.01) as was total specimen volume (143.40 vs 100.63 cm 3 ; p = 0.022)., Conclusions: CS can reduce the positive margin and re-excision rates without larger-volume resections and should therefore be considered a routine technique in BCS for early-stage breast cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The therapeutic effect of irradiation is thought to come from DNA damage that affects rapidly proliferating cancer cells; however, resistant cells rapidly initiate mechanisms to repair such damage. While DNA repair mechanisms responsible for cancer cell survival following DNA damage are understood, less is known about the epigenetic mechanisms resulting in resistance to radiotherapy. Although changes in DNA methylation are related to mechanisms of long-term resistance, it is more likely that the methylation state of a series of proteins could be responsible for the first-line of defense of cancer cells against irradiation. In this study, we observed that irradiation of breast cancer cells was accompanied by an overproduction in S-adenosylmethionine, which increases the activity of cellular methylases. We found that by activating PRMT1, irradiation triggers a BRCA1-dependent program that results in efficient DNA repair and inhibition of apoptosis. Depletion of PRMT1 in irradiated cells resulted in a switch of BRCA1 functions from repair and survival in the nucleus to activation of cell death signals in the cytoplasm. We conclude that by modulating the cellular localization of BRCA1, PRMT1 is an important regulator of the oncogenic functions of BRCA1, contributing to the epigenetic defense of breast cancer cells against ionizing radiation.

Background: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method., Methods: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan-Meier estimates in quartile groups of model predicted probabilities (MPP)., Results: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p < 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set., Conclusions: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.

Background: Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT., Methods: A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS)., Results: Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress., Conclusion: High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT.

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

Aims: The gold standard for detection of Sentinel Lymph Nodes (SLN) is a combined radioisotope and blue dye breast injection, using a gamma probe (GP). A new, non-radioactive method was developed, using a tracer (Sienna+(®)) of superparamagnetic iron oxide (SPIO) nanoparticles and a manual magnetometer (SentiMag(®)) (SM). The IMAGINE study was designed to show the non-inferiority of SM compared to GP, for the detection of SLN in breast cancer patients with SLN biopsy indication., Methods: From November 2013 to June 2014, 181 patients were recruited, and 321 nodes were excised and assessed ex-vivo. Readings from both SM and GP devices were recorded during transcutaneous, intraoperative, and ex-vivo detection attempts., Results: At the patient level, ex-vivo detection rates (primary variable) with SM and GP were 97.8% and 98.3% (concordance rate 99.4%). Transcutaneous and intraoperative detection rates were 95.5% vs 97.2%, and 97.2% vs 97.8% for SM and GP respectively (concordance rates > 97%). At the node level, intraoperative and ex-vivo detection rates were 92.5% vs 89.3% and 91.0% vs 86.3% for SM and GP respectively. In all cases the non-inferiority of SM compared to SM was shown by ruling out a predefined non-inferiority margin of 5%., Conclusions: Our study showed the non-inferiority of SM as compared to GP. Moreover, the ex-vivo and intraoperative detection rates at the node level were slightly higher with SM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: A controversial aspect of breast cancer management is the use of sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of SLNB after NCT to investigate the influence of initial nodal disease and the protocols applied., Methods: Prospective observational multicenter study in women with breast cancer, treated with NCT and SLNB post-NCT with subsequent lymphadenectomy. DT and FN rates were calculated, both overall and depending on the initial nodal status or the use of diagnostic protocols pre-SLNB., Results: No differences in DT between initial node-negative cases and positive cases were found (89.8 vs. 84.4%, P=.437). Significant differences were found (94.1 vs. 56.5%, P=0,002) in the negative predictive value, which was lower when there was initial lymph node positivity, and a higher rate of FN, not significant (18.2 vs. 43.5%, P=.252) in the same cases. The axillary study before SLNB and after the NCT, significantly decreased the rate of FN in patients with initial involvement (55.6 vs 12.5, P=0,009)., Conclusions: NCT means less DT and a higher rate of FN in subsequent SLNB, especially if there is initial nodal involvement. The use of protocols in axillary evaluation after administering the NCT and before BSGC, decreases the FN rate in these patients., (Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aim: One-Step Nucleic Acid Amplification (OSNA) can detect isolated tumour loads in axillary lymph nodes of breast cancer patients. We investigated the predictability of the non-sentinel lymph node (SLN) metastatic involvement (MI) based on the OSNA SLN assessment in surgical invasive breast cancer., Methods: We studied surgical breast invasive carcinoma patients, not taking neoadjuvant chemotherapy, having SLN positive by OSNA and having received axillary lymphadenectomy. Age, basic histopathological, immunohistochemical, SLN biopsy and lymphadenectomy data were compared between patients with or without MI of more than 2 non-SLN in both univariate and multivariate analyses. The discriminating capacity of the multivariate model was characterized by the ROC AUC., Results: 726 patients from 23 centers in Spain aged 55.3 ± 12.2 years were analysed. The univariate analysis comparing patients with or without MI of more than 2 non-SLN detected statistically significant differences in primary tumour size, multifocality, presence of lymphovascular infiltration, positive proliferation index with ki67, immunophenotype and logTTL (Tumour Total Load). The multivariate logistic analyses (OR (95% CI)) confirmed multifocality (2.16 (1.13-4.13), p = 0.019), lymphovascular infiltration (4.36 (2.43-7.82), p < 0.001) and logTTL (1.22 (1.10-1.35), p < 0.001) as independent predictors, and exhibit an AUC (95% CI) of 0.78 (0.72-0.83) with an overall fit (Hosmer-Lemeshow test) of 0.359. A change in the slope of both sensitivity and specificity is observed at about 10,000 copies/μL, without relevant changes in the Negative Predictive Values., Conclusions: Using OSNA technique, the MI of more than 2 non-SLN can be reliably predicted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Axillary lymph node status at the time of diagnosis is the most important prognostic indicator for women with breast cancer, and may influence management decisions. However, at present its role is controversial, as some groups recommend avoiding axillary lymph node dissection (ALND) in cases with metastasis of any size in the sentinel lymph nodes. Molecular analysis allows full examination of the sentinel lymph nodes in a short time period, discriminatation between macrometastasis, micrometastasis and isolated tumor cells, and helps to predict the performance of ALND. ALND may be the treatment of choice in some patients, even in cases of low-volume metastasis, as chemotherapy does not control regional disease well. In addition, the collection of metastatic cells, as well as the local immune surveillance, is susceptible to further molecular studies that will offer prognostic and predictive information, which may have an impact on therapeutic decisions, so that individualized treatments can be adequately designed.

Background: Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific transcription factors to gene promoters have emerged as important mechanisms for controlling gene expression. The aim of this study was to analyse the implications of these mechanisms and their molecular connections in the reactivation of RASSF1A in breast cancer., Methods: Compounds that modulate the intracellular concentration of adenosine, such as dipyridamole (DIPY), greatly increase the antiproliferative effects of 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG), a synthetic antifolate derived from the structure of tea catechins. Quantitative real-time PCR arrays and MALDI-TOF mass spectrometry indicated that this combination (TMCG/DIPY) induced apoptosis in breast cancer cells by modulating the methylation levels of DNA and proteins (such as E2F1), respectively. Chromatin immunoprecipitation (ChIP) assays were employed to confirm that this combination induced chromatin remodelling of the RASSF1A promoter and increased the occupancy of E2F1 at the promoter of this tumour suppressor gene., Results: The TMCG/DIPY combination acted as an epigenetic treatment that reactivated RASSF1A expression and induced apoptosis in breast cancer cells. In addition to modulating DNA methylation and chromatin remodelling, this combination also induced demethylation of the E2F1 transcription factor. The ChIP assay showed enhancement of E2F1 occupancy at the unmethylated RASSF1A promoter after TMCG/DIPY treatment. Interestingly, inhibition of E2F1 demethylation using an irreversible inhibitor of lysine-specific demethylase 1 reduced both TMCG/DIPY-mediated RASSF1A expression and apoptosis in MDA-MB-231 cells, suggesting that DNA and protein demethylation may act together to control these molecular and cellular processes., Conclusions/significance: This study demonstrates that simultaneous targeting of DNA and E2F1 methylation is an effective epigenetic treatment that reactivates RASSF1A expression and induces apoptosis in breast cancer cells.

Background: The aim of this paper is to determine the possible association between five different profiles of immunohistochemical expression related to clinical, histopathological and immunohistochemical known prognostic value variables for breast cancer., Material and Method: A total of 194 breast carcinoma tumour samples were studied. In this study five groups or immunohistochemical profiles were defined, based on expression of hormone receptors (oestrogen or progesterone) and/or Her2/neu (luminal-type A, luminal-type B, mixed profile, Her2/neu profile and triple-negative-type profile) and we studied whether there are differences between them with regard to clinical, histopathological and immunohistochemical variables that have a known prognostic significance., Results: In the series we found 134 (69%) cases corresponding to a luminal immunophenotype, of which 98 (50.5%) were from the luminal A group and 36 (18.6%) from luminal B. Twenty-nine cases (15.9%) were triple-negative, 18 (9.3%) mixed and 13 (6.7%) Her2/neu type. It is worth noting the relationship between the triple-negative and Her2/neu immunophenotypes and the more poorly differentiated histological forms (62% and 60%, respectively) and between the luminal A group and well-differentiated tumours (p = 0.008). Expression of ki67 was high in the triple-negative group (73.9%) and low in the luminal A group (26.3%; p = 0.001). The expression of p53 was also greater for the Her2/neu (55.5%) and triple-negative (60.8%) groups (p = 0.0005) than for the others., Conclusions: The subgroups without hormone receptor expression, with Her2/neu overexpression or without (triple-negative group), have characteristics associated with variables of a poorer prognosis. The lack of progesterone receptor expression also seems to be associated with these.

Objectives: The sentinel node is defined as the node with the highest probability of being involved in the case of lymphatic spread from a tumor. Accurate identification and biopsy of this node can avoid unnecessary lymphadenectomies. The aim of this study was to determine if there are differences in the number of isolated sentinel lymph nodes in breast cancer according to whether a mixed technique (vital dye plus isotopic tracer) or radiotracer alone is used and if there are differences in the detection of more than one lymphatic basin and in the number of lymphatic nodes depending on the site of tracer injection., Patients and Method: A total of 173 sentinel lymph node biopsies in 173 women with breast cancer were studied taking into account the technique (mixed [n = 109] or radiotracer alone [n = 64]) and the location of tracer injection (periareolar [n = 81], intra and/or peritumoral [n = 92]). The number of lymphatic basins and the number of sentinel nodes were compared among the distinct groups resulting from the combination of the 2 parameters., Results: Simultaneous drainage to both the axilla and internal mammary chain was more frequent with the intra-periareolar technique. The number of identified nodes was significantly higher when mixed techniques were compared, and was higher with periareolar injection than with the intra-peritumoral route., Conclusions: In breast cancer sentinel lymph node biopsy, the number of identified nodes is not influenced by the use of a mixed technique or radiotracer alone. However, the number of identified nodes is higher with the periareolar route than with the intra-peritumoral route. Intra-peritumoral injection of the tracer shows a higher frequency of internal mammary chain drainage than periareolar injection, although this difference was not statistically significant.