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Simple Summary: Stromal tumor infiltrating lymphocytes (sTIL) are a validated predictive and prognostic biomarker in non-luminal breast cancer. Our aim was to evaluate their clinical relevance in luminal (hormone receptor positive, HER2 negative) early breast cancer. Our results show that, although sTIL are associated with a better response to neoadjuvant chemotherapy, they are also associated with worse biological features (proliferation, higher stage) and poorer prognosis in luminal B breast cancer. TIL might improve prognostic stratification and contribute to therapeutic decision-making in the early high-risk setting of luminal B breast cancer. Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1–Q3 range (IQR), 0–10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02–1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33–17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy is routinely prescribed for women who undergo breast-sparing surgery for early breast cancers. Over the years, advancements in diagnosis and treatments have dramatically improved breast cancer outcomes, now approaching 100% survival at 5 years for those diagnosed at stage I with favorable clinical and molecular features. In this review, we discuss the investigations that are underway to identify women with low-risk cancers in whom radiation therapy can either be completely avoided or delivered in lower intensities. We also review ongoing clinical trials that are assessing if radiation therapy can increase the capacity of patients' anticancer immune responses and discuss if cancer cells that are shed in the blood can guide radiation decisions. Adjuvant whole breast irradiation after breast-conserving surgery is a well-established treatment standard for early invasive breast cancer. Screening, early diagnosis, refinement in surgical techniques, the knowledge of new and specific molecular prognostic factors, and now the standard use of more effective neo/adjuvant systemic therapies have proven instrumental in reducing the rates of locoregional relapses. This underscores the need for reliably identifying women with such low-risk disease burdens in whom elimination of radiation from the treatment plan would not compromise oncological safety. This review summarizes the current evidence for radiation de-intensification strategies and details ongoing prospective clinical trials investigating the omission of adjuvant whole breast irradiation in molecularly defined low-risk breast cancers and related evidence supporting the potential for radiation de-escalation in HER2+ and triple-negative clinical subtypes. Furthermore, we discuss the current evidence for the de-escalation of regional nodal irradiation after neoadjuvant chemotherapy. Finally, we also detail the current knowledge of the clinical value of stromal tumor-infiltrating lymphocytes and liquid-based biomarkers as prognostic factors for locoregional relapse. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most prevalent cancer in women and the leading cause of cancer-associated deaths. Although several therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for the treatment of advanced breast cancers. Unfortunately, systemic chemotherapy causes numerous side effects and damage to distal organs and requires high doses of drugs to achieve a therapeutic concentration in the tumor region. The use of nanosystems for drug delivery is a promising strategy to overcome these drawbacks. In this study, we developed Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing the chemotherapeutic drug Docetaxel, functionalized with a cyclic RGD tripeptide to allow the active targeting of αvβ3 integrins, which are overexpressed in breast cancer. We demonstrated that PLGAs effectively deliver the drug to breast cancer cells in preclinical models, and are more effective than free Docetaxel in hampering tumor progression, while reducing side effects. Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects. [ABSTRACT FROM AUTHOR]

Background. Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods. A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results. A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions. In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048). [ABSTRACT FROM AUTHOR]

Objective: To study the existing literature on the bra as a tool for well-being in women. Methodology: Review of the Turning Research into Practice, Cochrane Library Plus, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), BMi Best Practice and UpToDate databases in English and Spanish for the last 10 Last search in September 2021. Results: Of the 150 bibliographic references, 130 met the selection criteria. 12 articles were selected: 8 originals, 2 guidelines for action and 2 systematic review. The main results found were breast pain and causes, painful processes related to the bra, special situations such as pregnancy, lactation or breast surgeries, biomechanical alterations and the influence on quality of life related to depression and anxiety. Conclusions: There is no evidence that sagging breasts are caused by not wearing a bra. Nor is it between wearing a bra and an increased risk of breast cancer. Correct use of the bra was related to improvements in breast pain, biomechanical alterations and mood, breastfeeding, breast surgery and practice of impact sports. The bra garment is evaluated as a health tool in women. [ABSTRACT FROM AUTHOR]

Background. Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods. HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results. 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3–57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3–4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8–46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75–99%). Conclusion. This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study aims at highlighting the response to pertuzumab, trastuzumab and docetaxel treatment (THP), without using anthracycline, in patients with HER2-positive early breast cancer. We add evidence to the suitability of THP in real life to reach higher pathological complete response rates, with a good safety profile for patients. An exploratory analysis of the mutational status of PIK3CA was performed as well, and 21% mutated samples were identified, with overall higher pCR rates in PIK3CA mutant patients and, particularly, in those who were THP-treated. Our original results open the door to further studies focused on more in-depth analysis of the molecular and clinical features related to the response to anthracycline-free neoadjuvant treatment in HER2-positive early breast cancer patients. HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results. [ABSTRACT FROM AUTHOR]

Simple Summary: The miR200 family is involved in breast cancer progression. Our aim was to evaluate the predictive and prognostic role of miR-200c-3p, both in plasma and in tumor, in women with locally advanced and metastatic breast cancer. Our results show that plasma levels of miR-200c-3p are higher in these patients and might be used as a breast cancer marker. In patients treated with neoadjuvant chemotherapy, miR-200c-3p expression may also improve prognostic stratification beyond pathologic response and clinical stage. While the role of miR-200c in cancer progression has been established, its expression and prognostic role in breast cancer is not completely understood. The predictive role of miR-200c in response to chemotherapy has also been suggested by some studies, but only limited clinical evidence is available. The purpose of this study was to investigate miR-200c-3p in the plasma and primary tumor of BC patients. The study design included two cohorts involving women with locally advanced (LABC) and metastatic breast cancer. Tumor and plasma samples were obtained before and after treatment. We found that miR-200c-3p was significantly higher in the plasma of BC patients compared with the controls. No correlation of age with plasma miR-200c-3p was found for controls or for BC patients. MiR-200c-3p tumor expression was also associated with poor overall survival in LABC patients treated with neoadjuvant chemotherapy, independently of pathological complete response or clinical stage. Our findings suggest that plasmatic miR-200c-3p levels could be useful for BC staging, while the tumor expression of miR-200c-3p might provide further prognostic information beyond residual disease in BC treated with neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the recruitment of CAFs and TAMs. Our findings showed that, together with the expected overexpression of TME markers, DDR2 was upregulated in tumor samples. Besides, we uncovered that altered TME markers were linked to DDR2 expression in invasive BC patients. Consequently, DDR2 modulates the stromal reaction through CAFs and TAMs infiltration and could be used as a potential worse prognostic factor in the treatment response of invasive BC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether repeated oral cryotherapy was effective in reducing nausea, vomiting, oral mucositis, and oral pain in patients with breast cancer receiving chemotherapy during the 1st, 2nd, and 3rd rounds of chemotherapy for the first time. Methods: A nonequivalent control group non-synchronized design was used. The experimental group (n=21) received oral cryotherapy that applied a 2x2x2 cm ice cube in the mouth for 30 minutes at each chemotherapy. Both experimental group and control group (n=20) received oral care educations. Nausea, vomiting, oral mucositis and oral pain were measured on 5 days, 14 days, and 21 days after each chemotherapy. Data were collected from July 2019 to April 2020 at a university hospital in Korea, and analyzed using the SPSS WIN 25.0 software package. Results: There was a significant difference between the experimental and control groups in the nausea·vomiting score, oral mucositis grade, and oral pain score. Oral cryotherapy was confirmed to be effective in delaying nausea and vomiting. It has been shown that stomatitis and oral pain are related. Conclusion: For breast cancer patients receiving chemotherapy, it is recommended to apply oral cryotherapy as a nursing intervention to reduce nausea, vomiting, oral mucositis, and oral pain. [ABSTRACT FROM AUTHOR]

Background. Everolimus has been shown to overcome endocrine resistance in hormone receptor positive advanced breast cancer patients. Predictive biomarkers of everolimus efficacy have been investigated in primary breast cancer tissue without finding univocal results. The goal of this study was to investigate the mutational burden in the metastatic site of endocrine-resistant tumors treated with everolimus plus exemestane. Patients and Methods. Mass Array Sequenom platform was used to analyse genetic status of 18 cancer-related genes in 25 archival tumor specimens from metastatic lesions and available primary matched breast cancer tissue of patients treated with everolimus and exemestane for advanced disease. An exploratory analysis of everolimus efficacy in terms of progression free survival benefit and single gene mutation was carried out. Results. The overall detection rate of mutation was 30% and 38% from metastatic and primary breast cancer samples, respectively. AKT1E17K was the most frequent mutated gene. No primary breast cancer and matched relapse maintained the same mutation profile. Considering molecular pathways, the most of the genes belong to PI3K pathway (AKT1E17K, PI3KCAE545K, and KITG565R,S709F). In patients with detected mutations in breast and/or recurrence tissue the median PFS was 5,6 months while in the subgroup of patients with no mutations the median PFS was 7,5 months. Conclusions. The mutational status of breast cancer recurrence allows the identification of some genes potentially correlating tumor response/resistance to everolimus. The most frequently mutated genes were involved in the PI3K/AKT/mTOR pathway highlighting that the deregulation of this pathway in the relapse plays a crucial role in the mechanisms of everolimus resistance/sensitivity. Owing to the small sample size and the retrospective nature of the study, these correlations need to be validated in a large prospective study. [ABSTRACT FROM AUTHOR]

Background: Fluorine-18 fluorodeoxyglucose (F-18 FDG)-positron emission tomography/computed tomography (PET/CT) is widely used in most malignancy workups, including detection, differential diagnosis, staging and/or restaging, therapeutic decisionmaking, follow-up, and prognosis. Objectives: The aim of this study was to evaluate the usefulness of F-18 FDG-PET/CT for predicting breast cancer molecular subtypes. Patients and Methods: Sixty-six patients with pathologically proven invasive breast carcinoma (IBC) underwent F-18 FDG-PET/CT imaging for tumor staging. The maximum standardized uptake value (tumor SUVmax) of the IBC and mean SUVs of the liver and spleen (liver and spleen SUVmean) were measured. Molecular subtype was determined according to genomic analysis. The tumor SUVmax, tumor-to-liver SUV ratio, and tumor-to-spleen SUV ratio were correlated with molecular subtype data. Results: Logistic analysis demonstrated that only the tumor-to-liver SUV ratio was a significant parameter for human epidermal growth factor type 2 (HER2)-positive subtype identification (P = 0.0049). The sensitivity, specificity, and area under the receiver-operating-characteristic curve (AUC) of this parameter for HER2-positive subtype detection were 83%, 79%, and 0.87, respectively. Conclusion: The tumor-to-liver SUV ratio appears to be useful for HER2-positive subtype identification, thus indicating the potential use of F-18 FDG-PET/CT as an imaging biomarker that could facilitate the clinical management of patients with breast cancer. [ABSTRACT FROM AUTHOR]

Optimization of adjuvant systemic therapy in women with early-stage hormone receptor-positive breast cancer includes the consideration of chemotherapy and ideal type and duration of anti-hormone therapy. The use of gene expression profiling as a predictive marker for determining benefit to chemotherapy has become an important consideration when recommending chemotherapy in patients with early stage hormone receptor-positive breast cancer. Recent results from the TAILORx and MINDACT studies provide the first prospective data, designed to give more conclusive guidance on assays. Defining the optimal adjuvant anti-hormone therapy, administered after the consideration of chemotherapy, is a constantly evolving field, in which factors such as menopausal status, drug type, and duration of therapy are carefully considered. New data from the MA17R study and the 2016 San Antonio Breast Cancer Symposium (SABCS) provide early evidence that demonstrates the benefit of extending the duration of aromatase inhibitors builds on previous studies investigating extended tamoxifen or sequential therapies between these 2 drug classes. Indeed, modern breast oncology care for patients with early stage hormone receptor-positive disease involves individualizing recommendations based on clinical presentation and genomic assays to provide optimal chemotherapy, and anti-hormone regimens. This manuscript will provide updates on approaches to gene expression analysis and extended aromatase inhibitors in early breast cancer, focusing on several recent presentations and publications. [ABSTRACT FROM AUTHOR]

Background: This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. Methods: An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. Results: In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. Conclusions: Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple Summary: We extracted known interactions between metastasis suppressors and their regulators from scientific studies. Next, we used publically available data of drug treatments to identify which of them potentially perturbs these interactions. Finally, we studied the effect of several of these drugs on a particular metastasis suppressor called RKIP and found that our model accurately predicted its regulation in breast cancer cells. Our approach can discover alternative mechanisms of existing cancer drugs and repurpose them in different disease types. Drug screening strategies focus on quantifying the phenotypic effects of different compounds on biological systems. High-throughput technologies have the potential to understand further the mechanisms by which these drugs produce the desired outcome. Reverse causal reasoning integrates existing biological knowledge and measurements of gene and protein abundances to infer their function. This approach can be employed to appraise the existing biological knowledge and data to prioritize targets for cancer therapies. We applied text mining and a manual literature search to extract known interactions between several metastasis suppressors and their regulators. We then identified the relevant interactions in the breast cancer cell line MCF7 using a knockdown dataset. We finally adopted a reverse causal reasoning approach to evaluate and prioritize pathways that are most consistent and responsive to drugs that inhibit cell growth. We evaluated this model in terms of agreement with the observations under treatment of several drugs that produced growth inhibition of cancer cell lines. In particular, we suggested that the metastasis suppressor PEBP1/RKIP is on the receiving end of two significant regulatory mechanisms. One involves RELA (transcription factor p65) and SNAI1, which were previously reported to inhibit PEBP1. The other involves the estrogen receptor (ESR1), which induces PEBP1 through the kinase NME1. Our model was derived in the specific context of breast cancer, but the observed responses to drug treatments were consistent in other cell lines. We further validated some of the predicted regulatory links in the breast cancer cell line MCF7 experimentally and highlighted the points of uncertainty in our model. To summarize, our model was consistent with the observed changes in activity with drug perturbations. In particular, two pathways, including PEBP1, were highly responsive and would be likely targets for intervention. [ABSTRACT FROM AUTHOR]