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Simple Summary: Exercise is well known to decrease the risk of breast cancer. The cellular processes that contribute to exercise-induced cancer prevention are less known. We conducted an exercise training study in rats given a chemical to induce breast cancer. Exercise increased the length of time to development of breast cancer in rats. However, when we gave the rats an antibody which binds to a certain cellular protein (oncostatin M), exercise-induced protection against breast cancer was not observed. These observations may be useful in future studies as the oncostatin M protein is produced by muscles. Thus, these results support a link between muscle use during exercise and breast cancer prevention. Future studies may examine oncostatin M and other proteins produced by exercising muscles for their potential role in breast cancer prevention. Moderate-to-vigorous-intensity physical activity decreases the risk of breast cancer. The muscle-derived cytokine (myokine), oncostatin M (OSM), has been shown to decrease breast cancer cell proliferation. We hypothesized that OSM is involved in physical activity-induced breast cancer prevention, and that OSM antibody (Anti-OSM) administration would mitigate the effect of physical activity in a rat model of mammary carcinoma. Female Sprague Dawley rats were injected with 50 mg/kg N-methyl-N-nitrosourea to induce mammary carcinogenesis. During the 20-week study, rats were exercise trained (EX) or remained sedentary (SED). Additional groups were treated with Anti-OSM antibody (SED + Anti-OSM and EX + Anti-OSM) to explore the impact of OSM blockade on tumor latency. Exercise training consisted of treadmill acclimation and progressive increases in session duration, speed, and grade, until reaching 30 min/day, 20 m/min at 15% incline. Experimentally naïve, age-matched, female rats also completed an acute exercise test (AET) with time course blood draws to evaluate OSM plasma concentrations. Relative tumor-free survival time was significantly longer in EX animals (1.36 ± 0.39) compared to SED animals (1.00 ± 0.17; p = 0.009), SED + Anti-OSM animals (0.90 ± 0.23; p = 0.019), and EX + Anti-OSM animals (0.93 ± 0.74; p = 0.004). There were no significant differences in relative tumor latency between SED, SED + Anti-OSM, or EX + Anti-OSM animals. Following the AET, OSM plasma levels trended higher compared to baseline OSM levels (p = 0.080). In conclusion, we observed that exercise-induced delay of mammary tumor development was mitigated through Anti-OSM administration. Thus, future studies of the OSM mechanism are required to lay the groundwork for developing novel chemo-prevention strategies in women who are unable or unwilling to exercise. [ABSTRACT FROM AUTHOR]

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed. [ABSTRACT FROM AUTHOR]

Objective: Differences in individual muscle/fat volumes may change the effectiveness of chemotherapy. In this study, the relationship between trunkal muscle and fat volume and body mass index (BMI) obtained before receiving neoadjuvant chemotherapy (NCT) in patients with breast cancer and complete pathological response (pCR) was investigated. Materials and Methods: The volumes of psoas, abdominal and paraspinal muscles, and trunkal subcutaneous and visceral fat were calculated using CoreSlicer AI 2.0 opensource program from the F-18 fluorodeoxyglucose positron emission tomography/computed tomography (CT) and CT images before NCT and postoperative pCR rates to NCT were recorded. Muscle/fat volumes and BMI prior to NCT were compared in terms of pathological pCR rates. Patients were followed up regularly for recurrence and survival. Results: Ninety-three patients were included with median (range) values for age, BMI, and body weights of 48 (28-72) years, 27 (16.8-51.6) kg/m2, and 71.94 (43-137) kg, respectively. The median follow-up time was 18.6 (6.7-59.6) months. No significant correlation was found between total muscle or fat volumes of patients with and without pCR. BMI [26.2 (16.8-51.6) kg/m2 vs. 24.6 (20.3-34.3) kg/m2, p = 0.03] and pCR rates in patients with low rightpsoas muscle volume [11.74 (7.03-18.51) vs. 10.2 (6.71-13.36), p = 0.025] were significantly greater. A significant relationship was found between right psoas muscle volume and disease-free survival (DFS) (11.74 cm3 (7.03-18.51) vs. 10.2 cm3 (6.71-13.36), p = 0.025). However, no significant relationship was detected between total muscle-fat volume, BMI and overall survival and DFS (p>0.05). Conclusion: This is the first published study investigating the relationship between the pCR ratio and body muscle and fat volume measured by CoreSlicer AI 2.0 in patients with breast cancer who received NCT. No correlation was found between the pCR ratio and total muscle plus fat volume. However, these results need to be validated with larger patient series. [ABSTRACT FROM AUTHOR]

Objective: The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. Materials and Methods: This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Results: Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. Conclusion: In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion. [ABSTRACT FROM AUTHOR]

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNBpositivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNBpositivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB. [ABSTRACT FROM AUTHOR]

The advent of taxane-based chemotherapy has revolutionized breast cancer care. This advance has helped improve the response to downstaging tumors that might otherwise be inoperable. It has also helped in rendering clinically (cN+) positive lymph nodes (LNs) pathologically negative (ypN0). The standard of care for cN+ patients included post-mastectomy radiotherapy (PMRT), regardless of the response to neoadjuvant chemotherapy. However, PMRT in patients with 1-3 positive LNs still lacks definitive guidelines. Numerous retrospective results have been inconclusive about the benefit of PMRT on survival in patients with 1-3 positive LNs. This pooled analysis attempts to reach a consensus. The PubMed database was searched through October 2023. The search yielded 27 papers, of which 11 satisfied the inclusion criteria. The locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) for each study were tabulated when given, and two groups were created, the PMRT and NO PMRT, respectively. The results were then pooled for analysis. The total number of patients was 8340, 4136 in the PMRT group, and 4204 in the NO PMRT group, respectively. The LRRFS, DFS, and OS were 96.9%, 82.1%, and 87.3% for the PMRT group and 93.2%, 79.6%, and 84.8% for the NO PMRT group, respectively. There was no statistical significance in LRRFS, DFS, or OS between the two groups (p = 0.61, p = 0.61, and p = 0.38, respectively). PMRT does not seem to confer survival benefits in patients with pN1 rendered ypN0 for stages T1-3. This pooled analysis's findings should be confirmed prospectively with a longer period of follow-up. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry (IHC) plays an important role in the management and outcome of breast cancer. It has been observed that the responses to same chemotherapy or hormone therapy are different among cases of breast cancer. Despite the recognition of the IHC markers and appropriate treatment, poor response or relapse can be attributed to the discordance between marker status of breast tumors and axillary lymph nodes. Therefore, our aim is to assess the molecular markers in primary breast cancer/tumor (PBT) and metastatic axillary lymph nodes (ALN) and their correlation with outcome in patients undergoing treatment for carcinoma breast in our hospital. Methods: This Prospective Observational study was done in an institution in northern India dedicated for people of low socioeconomic strata. Study was done over a period of two years. 85 patients with operable breast carcinoma without neoadjuvant chemotherapy were included in the study. Results: Mean value of age (years) of patients was 50.73 ± 9.8 Majority (96.47%) of patients had invasive breast carcinoma -- no special type. 77.65% of patients had stage IIA breast carcinoma at the time of presentation. IHC of primary tumor correlated with that of axillary lymph nodes mostly and discordance was statistically insignificant. Conclusion: We concluded that discordance in immunohistochemistry profile of primary breast tumor and axillary lymph nodes are statistically insignificant and it is not the reason of poor outcome in certain cases of carcinoma breast. [ABSTRACT FROM AUTHOR]

Simple Summary: DNA repair inhibition constitutes a promising anticancer strategy, particularly in triple-negative breast cancer (TNBC), ovarian cancer and pancreatic ductal adenocarcinoma (PDAC). XGAc is a xanthonoside previously described as a potent cancer cell growth inhibitor. Herein, we aimed to evaluate the antitumor activity of XGAc in TNBC, ovarian cancer and PDAC cells, either alone or in combination with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib. XGAc exhibits antiproliferative activity in TNBC, ovarian cancer and PDAC cells, also proving to be effective against patient-derived ovarian cancer cells and drug-resistant cancer cells. XGAc inhibited cancer cell migration, induced apoptosis and S-phase cell cycle arrest, and triggered genotoxicity by inhibiting the expression of homologous recombination DNA repair proteins in TNBC, ovarian cancer and PDAC cells. Importantly, XGAc displayed synergistic effects with olaparib, demonstrating its potential in combination therapy. Altogether, XGAc reveals itself to be a valuable anticancer agent for hard-to-treat cancers. Dysregulation of the DNA damage response may contribute to the sensitization of cancer cells to DNA-targeting agents by impelling cell death. In fact, the inhibition of the DNA repair pathway is considered a promising anticancer therapeutic strategy, particularly in combination with standard-of-care agents. The xanthonoside XGAc was previously described as a potent inhibitor of cancer cell growth. Herein, we explored its antitumor activity against triple-negative breast cancer (TNBC), ovarian cancer and pancreatic ductal adenocarcinoma (PDAC) cells as a single agent and in combination with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib. We demonstrated that XGAc inhibited the growth of TNBC, ovarian and PDAC cells by inducing cell cycle arrest and apoptosis. XGAc also induced genotoxicity, inhibiting the expression of DNA repair proteins particularly involved in homologous recombination, including BRCA1, BRCA2 and RAD51. Moreover, it displayed potent synergistic effects with olaparib in TNBC, ovarian cancer and PDAC cells. Importantly, this growth inhibitory activity of XGAc was further reinforced in a TNBC spheroid model and in patient-derived ovarian cancer cells. Also, drug-resistant cancer cells showed no cross-resistance to XGAc. Additionally, the ability of XGAc to prevent cancer cell migration was evidenced in TNBC, ovarian cancer and PDAC cells. Altogether, these results highlight the great potential of acetylated xanthonosides such as XGAc as promising anticancer agents against hard-to-treat cancers. [ABSTRACT FROM AUTHOR]

Objective • To explore the use of 3-dimensional speckletracking echocardiography (3DSTE) to evaluate changes in left ventricular function in patients with breast cancer after anthracycline chemotherapy. Methods • The clinical data of 30 patients with breast cancer diagnosed by pathology at The Third Affiliated Hospital of Qiqihar Medical University from December 2020 to December 2022 were collected for retrospective analysis. All patients received anthracycline chemotherapy, and serum cardiac troponin T (cTnT) concentrations were measured within 24 to 48 hours before chemotherapy and after 1 cycle and 4 cycles of chemotherapy. Then, conventional ultrasonography, routine echocardiography, and 3DSTE were performed to obtain dynamic images and parameters such as left ventricular global longitudinal strain, global area strain, global circumferential strain, global radial strain, and twist values. The myocardial comprehensive index was calculated to compare changes before and after anthracycline chemotherapy. A receiver operating characteristic curve was created for each parameter, and the areas under the curves were calculated. Results • Except for left ventricular end-diastolic diameter and end-diastolic interventricular septum thickness, the other conventional ultrasonography parameters differed at the 3 chemotherapy time points tested (all P<.001). The parameters as measured by 3DSTE decreased with an increased cumulative dose of anthracycline drugs, and the values differed at the different time points (all P<.001); the MCI value decreased the most. The serum cTnT concentrations of 9 patients after 4 cycles of chemotherapy were higher than the normal range, and the serum cTnT concentrations differed at the different chemotherapy time points (P<.001). Receiver operating characteristic curve analysis showed that the area under the curve value for MCI was higher than other quantitative parameters of imaging; for MCI, the area under the curve was 0.799, the Youden index was 0.683, the sensitivity was 77.80%, and the specificity was 90.50%. Conclusion • 3DSTE is helpful for early detection of damage to left ventricular function in patients with breast cancer treated with anthracycline drugs, and MCI is the most sensitive observation index among the parameters tested. [ABSTRACT FROM AUTHOR]

The article titled "Palliative, supportive and hospice care: education is important" emphasizes the significance of education in palliative, supportive, and hospice care. It presents a collection of original articles and reviews that cover various topics within this field. These include chronic pain evaluation in breast cancer patients, the impact of COVID-19 on individuals with dementia, and the self-efficacy of healthcare professionals in advance care planning. Additionally, the article includes a review on decision aid programs for prostate cancer patients. The text also provides information on upcoming conferences and postgraduate education opportunities in palliative care. [Extracted from the article]

Purpose: Cancer is the leading challenge to human health since the dawn of early Egyptianmanuscripts, where they found tumour from fossils in the modernized 20th century. Increasingrate of incidence and death from cancer in the past few years is thought provoking. Among alltype of cancers, breast cancer is very common among women and diverse in character. Drugresistance is the challenging aspect for traditional chemotherapy.Methods: Data was collected from online platform without any time restriction. After screeningand evaluation, 66 articles were considered for this study. This review is a summarized collectionof information from published studies on human genes associated with drug resistance in breastcancer treatment.Results: Analysis of these findings highlights the importance of MAP kinase and ABC genefamilies in creating resistance barriers. Genes involved in cell cycle alteration, apoptosis, andhippo pathway were also linked with drug resistance particularly in breast cancer.Conclusion: The exact mechanism of chemotherapy resistance is still unresolved andunexplained the drug resistance seen in breast cancer patients were multifactorial. Druginduced up regulation or down regulation of genes contributes unusual protein expression andultimately leads to resistance. The ultimate focus of this review is to identify the genes havingpivotal role in chemotherapy resistance in breast cancer.

Abstract Background Multi-drug delivery system based on polymer carrier is emerging for alleviating dose-limiting toxicities of first-line cytotoxic anticancer drugs, such as doxorubicin (DOX) for breast cancer chemotherapy. By co-loading the premium natural antioxidant salvianolic acid A (SAA) through colloidal self-assembly of amphiphilic copolymer, we herein developed CPMSD, a complex polymeric micellar system to overcome cardiotoxicity associated with DOX. Results Optimal formulation was obtained by DOE study and CPMSD micelles were well constructed by using mPEG-PCL for entrapment at a drug–carrier mass ratio of 1:5 and DOX–SAA mass ratio of 1:4. Molecular dynamics simulation revealed the ratiometrical co-encapsulation of SAA into the hydrophobic cavity but DOX to ball-shaped surface of micelles due to hydrophilicity. Characterization study manifested favorable biopharmaceutical properties, such as small and uniform particle size, fairly high drug loading capacity, as well as good colloidal stability and controlled drug release. CPMSD maintained anticancer efficacy of DOX and the action mechanism, which did not be affected by co-administering SAA. More to the point, it was of great benefit to systemic safety and cardioprotective effect against oxidative stress injuries associated with DOX in tumor-bearing mice. Conclusions All the findings substantiated that CPMSD would be a promising multifunctional nanosystem of DOX for breast cancer chemotherapy.

Objective: The purpose of this prospective study was to assess the value of neoadjuvant chemotherapy with paclitaxel in the treatment of breast cancer. Methods: There were 88 diagnosed breast cancer patients altogether, 44 in each of the two groups (paclitaxel group and control group). To verify eligibility, thorough clinical, radiological, and laboratory evaluations were made. The reduction of tumor size, pathological reactions, and safety profiles were evaluated. To compare results between groups, statistical tests were used during data processing. Results: At 12 and 24 weeks, the paclitaxel group showed significantly smaller tumor sizes than the control group. In the paclitaxel group, complete pathological responses were more common, indicating efficient tumor regression. The side effects of paclitaxel therapy were generally well-tolerated and controllable. Conclusion: In conclusion, patients with breast cancer showed encouraging improvements in histological responses and tumor size after neoadjuvant paclitaxel treatment. These results suggest the potential advantages of using paclitaxel in neoadjuvant therapy protocols, perhaps making breastconserving surgery more feasible. In order to provide more individualized treatments, future research should investigate long-term outcomes and biomarkers indicative of paclitaxel sensitivity. [ABSTRACT FROM AUTHOR]

At present, the clinicopathological features, optimal treatment patterns, and prognosis of breast metaplastic squamous cell carcinoma (SCC) are not fully understood and are still controversial. Here, we report a 56‐year‐old female patient with breast infiltrating ductal carcinoma with axillary lymph node metastasis of metaplastic SCC admitted to our hospital. Their homology was clarified by comparing the gene mutation results of the two lesions, that is, the axillary lymph node lesion was a metastasis of breast metaplastic SCC. We treated the patient with Poly ADP‐ribose Polymerase (PARP) inhibitors in combination with immune checkpoint inhibitors (ICIs) and found that she could achieve clinical benefit from the combination regimen. We reported a successful diagnosis and treatment of this rare refractory disease and reviewed the literature on the characteristics, pathogenesis, and advances in the diagnosis and treatment of breast metaplastic SCC. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is the leading challenge to human health since the dawn of early Egyptian manuscripts, where they found tumour from fossils in the modernized 20th century. Increasing rate of incidence and death from cancer in the past few years is thought provoking. Among all type of cancers, breast cancer is very common among women and diverse in character. Drug resistance is the challenging aspect for traditional chemotherapy. Methods: Data was collected from online platform without any time restriction. After screening and evaluation, 66 articles were considered for this study. This review is a summarized collection of information from published studies on human genes associated with drug resistance in breast cancer treatment. Results: Analysis of these findings highlights the importance of MAP kinase and ABC gene families in creating resistance barriers. Genes involved in cell cycle alteration, apoptosis, and hippo pathway were also linked with drug resistance particularly in breast cancer. Conclusion: The exact mechanism of chemotherapy resistance is still unresolved and unexplained the drug resistance seen in breast cancer patients were multifactorial. Drug induced up regulation or down regulation of genes contributes unusual protein expression and ultimately leads to resistance. The ultimate focus of this review is to identify the genes having pivotal role in chemotherapy resistance in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Multi-drug delivery system based on polymer carrier is emerging for alleviating dose-limiting toxicities of first-line cytotoxic anticancer drugs, such as doxorubicin (DOX) for breast cancer chemotherapy. By co-loading the premium natural antioxidant salvianolic acid A (SAA) through colloidal self-assembly of amphiphilic copolymer, we herein developed CPMSD, a complex polymeric micellar system to overcome cardiotoxicity associated with DOX. Results: Optimal formulation was obtained by DOE study and CPMSD micelles were well constructed by using mPEG-PCL for entrapment at a drug–carrier mass ratio of 1:5 and DOX–SAA mass ratio of 1:4. Molecular dynamics simulation revealed the ratiometrical co-encapsulation of SAA into the hydrophobic cavity but DOX to ball-shaped surface of micelles due to hydrophilicity. Characterization study manifested favorable biopharmaceutical properties, such as small and uniform particle size, fairly high drug loading capacity, as well as good colloidal stability and controlled drug release. CPMSD maintained anticancer efficacy of DOX and the action mechanism, which did not be affected by co-administering SAA. More to the point, it was of great benefit to systemic safety and cardioprotective effect against oxidative stress injuries associated with DOX in tumor-bearing mice. Conclusions: All the findings substantiated that CPMSD would be a promising multifunctional nanosystem of DOX for breast cancer chemotherapy. [ABSTRACT FROM AUTHOR]

The application of nanomedicine represents an innovative approach for the treatment in the modern field of cancer chemotherapy. In the present research work, tamoxifen citrate loaded nanolipid vesicles were prepared conjugated with phosphoethanolamine as the linker molecule, and the specific antibody was tagged with the linker molecule on the bilayer surface of the vesicles. The main objective of this study is to determine the efficacy and biological behavior of antibody conjugated nanoliposome in breast cancer cell lines. Percentage of drug loading and loading efficiency was done and their results were compared to theoretical drug loading. The average diameter of those vesicles was within the 100 nm range, which is revealed in FESEM and TEM images and their lamellarity was observed in cryo-TEM images. The hydrodynamic diameter was done by particle size analysis and the surface charge was determined by the zeta potential parameter. Predominant cellular uptake was observed for antibody conjugated nanolipid vesicles in MCF-7 and MDA-MB-453 human breast cancer cell lines. A cellular apoptosis assay was conducted by flow cytometer (FACS). All experimental data would be more beneficial for the treatment of breast cancer chemotherapy. Further studies are warranted to investigate the efficacy and safety of antibody conjugated nanolipid vesicles in vivo for breast cancer animal model. [ABSTRACT FROM AUTHOR]

Introduction: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2–positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021. Case series: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder. Management and outcome: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy. Discussion: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib. [ABSTRACT FROM AUTHOR]

Breast cancer is a major threat worldwide. Hibiscus sabdariffa is widely consumed as beverage in sub-Saharan Africa for its anticancer potential. The present study therefore aimed at scientifically verifying its anticancer effect in rats. For this, 48 Wistar rats (∼55 days) were treated either with tamoxifen at 3.3 mg/kg BW (standard) or with a decoction of H. sabdariffa (125, 250, and 500 mg/kg BW) or distilled water (vehicle). Breast cancer was induced by a single dose of 50 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA). At the end of the 21 weeks of treatment, the tumor incidence, tumor morphology, histopathology, as well as some biochemical parameters in the tumors were assessed. As a result, 86% of DMBA's rats developed mammary tumors. The H. sabdariffa extract (125 and 250 mg/kg) reduced tumor incidence by 63% and 75%, respectively; inhibited tumor burden by 84.86% and 38.78%, respectively, and decreased tumor volume by more than 72% compared to the DMBA group. It also protected rats against DMBA-induced diffuse breast neoplasia, and the optimal effect was recorded at 125 mg/kg. Furthermore, it significantly increases the SOD activity and decreases the MDA level. In summary, H. sabdariffa has antibreast tumor and antioxidant properties in rats, which could justify its common use to treat cancer. [ABSTRACT FROM AUTHOR]

Introduction: The oncotype DX recurrence score (ODX-RS) is a validated 21-gene assay that can quantify the recurrence risk and assess the likelihood of adjuvant chemotherapy benefit in breast cancer. The presence of lymphovascular invasion (LVI) in breast cancer patients is regarded as a predictor for worse prognosis. This study sought to explore the association of ODX-RS with LVI in oestrogen receptor-positive, human epidermal growth factor receptor--2-negative, low-burden nodal disease, early breast cancer. Material and methods: After clinical improvement unit approval, an institutional database was queried to identify the breast cancer cases diagnosed in the period between 2017-2021 that fulfilled the inclusion criteria. The total resected tumours comprised 107 in 102 patients (5 patients had bilateral disease). The data related to patients' age and tumour grade, LVI detection, nodal status, and ODX-RS were analysed. Results: Lymphovascular invasion was identified in 32.6% of 107 tumours. In the age group > 50 years, 13 tumours had lymphovascular invasion (LVI +ve), 9 tumours had ODX-RS < 15 (69%), and only one tumour (8%) had ODX-RS ≤ 25, and this is associated with substantial chemotherapy benefit. In the age group ≤ 50 years, 21 tumours were LVI +ve, and 18 tumours had ODX-RS ≤ 25 (86%), which is associated with no chemotherapy benefit; only 3 tumours (14%) had ODX-RS > 25, and this indicated substantial chemotherapy benefit. Conclusions: This study revealed that in the targeted patient population lympho-vascular invasion did not have a statistically significant impact on ODX-RS (p = 0.29). [ABSTRACT FROM AUTHOR]

Introduction: Adermatoglyphia is defined as the medical condition clinically diagnosed to those who have a congenital or acquired loss of the epidermal ridges on the fingertips, commonly known as fingerprints. Capecitabine, a fluoropyrimidine, is the treatment of choice in a myriad of tumors and has occasionally been reported to cause adermatoglyphia as a secondary effect upon its use. Case Report: A 52-year-old female patient, diagnosed with stage IV metastatic left breast cancer with extension to bone in late 2011 reported upon biopsy a hormone receptor positive Her2 negative ductal carcinoma. After initial treatment with a combined radiotherapy and chemotherapy palliative treatment, hepatic and lung metastasis progression obliged capecitabine oral intake. In 2018, after two years on the fluoropyrimidine (capecitabine), the patient reported adermatoglyphia. Management & Outcome: The patient opted to continue taking the medication, since such treatment was working with no other meaningful side effects. Her last work-up studies continue to show complete lung and liver response with stable bone disease. Discussion: Capecitabine is a common drug in the therapy against metastatic breast cancer due to its manageable safety profile. Hand-foot syndrome is a frequent side effect caused by this drug, with dosage adjustment recommended with progression of symptoms. Recent publications have reported adermatoglyphia as a rare side effect of capecitabine use. Upon further examination through dermatoscopy and biopsy, the patient was evidenced to have lost the epidermal ridges that form fingerprints. A score of 9 on the Naranjo scale confirmed to be a consequence of the administration of capecitabine. [ABSTRACT FROM AUTHOR]

Natural products based novel crown ethers have been prepared by employing biologically active natural structures including tetrahydroisoquinoline, chrysin and biochanin-A as the side arms. The resulting crown scaffolds were evaluated for their anticancer potential against two cancer cell lines i.e. NCI-H460 (non-small lung carcinoma), MCF-7 (breast adenocarcinoma). The comparative study showed that the addition of crown scaffold put marked effects on antiproliferative profile of parent natural precursors and is significant for lung carcinoma in particular. Biochanin-A derived crown ether showed three (03) folds higher antiproliferative activity (IC50 - 6.08 ± 0.07 mM) against lung carcinoma as compared to standard drug cisplatin (IC50 - 19.00 ± 1.24 μM). Cytotoxic trends for NIH-3T3 cell lines were also examined and found reduced as compared to parent natural structures. Hence, these findings could open a new pathway towards developing effective carcinostatic drugs. [ABSTRACT FROM AUTHOR]

The article provides information on a case of a 65-year-old female with stage 4 invasive ductal carcinoma of the breast who developed carcinoma en cuirasse and systemic sclerosis as skin manifestations. The patient's condition presented challenges in determining the underlying cause, with possibilities including direct skin infiltration of tumor cells, paraneoplastic phenomenon, or chemotherapy-induced scleroderma.

Background: Ductal carcinoma in situ (DCIS) of breast is the noninvasive lesion that has propensity to progress to the malignant form. At present, it is still unknown which lesions can potentially progress to invasive forms. In this study, we aimed to identify key lncRNAs involved in DCIS growth.Methods: We employ disease-related lncProfiler array to identify IPW in specimens of DCIS and matching control samples and validate the observations in three DCIS-non-tumorigenic cell lines. Further, we examine the mechanism of IPW action and the downstream signaling in in vitro and in vivo assays. Importantly, we screened a library containing 390 natural compounds to identify candidate compound selectively inhibiting IPW low DCIS cells.Results: We identified lncRNA IPW as a novel tumor suppressor critical for inhibiting DCIS growth. Ectopic expression of IPW in DCIS cells strongly inhibited cell proliferation, colony formation and cell cycle progression while silencing IPW in primary breast cells promoted their growth. Additionally, orthotropic implantation of cells with ectopic expression of IPW exhibited decreased tumor growth in vivo. Mechanistically, IPW epigenetically enhanced miR-29c expression by promoting H3K4me3 enrichment in its promoter region. Furthermore, we identified that miR-29c negatively regulated a stemness promoting gene, ID2, and diminished self-renewal ability of DCIS cells. Importantly, we screened a library containing 390 natural compounds and identified toyocamycin as a compound that selectively inhibited the growth of DCIS with low expression of IPW, while it did not affect DCIS with high IPW expression. Toyocamycin also suppressed genes associated with self-renewal ability and inhibited DCIS growth in vivo.Conclusion: Our findings revealed a critical role of the IPW-miR-29c-ID2 axis in DCIS formation and suggested potential clinical use of toyocamycin for the treatment of DCIS. [ABSTRACT FROM AUTHOR]

Aim: Our study prospectively evaluated dental development in children exposed to chemotherapy in utero compared with unexposed controls. Design: Women who received chemotherapy while pregnant were enrolled in a research registry. After age two, each child's dentist was asked to complete a questionnaire about dental abnormalities and malformations, as well as for their unexposed siblings. Multivariate linear regression adjusting for age was used to compare the groups. Results: Dental information was received for 67 exposed children and 59 controls. The majority of mothers were treated for breast cancer (79.1%) and primarily received doxorubicin (89.6%) and cyclophosphamide (80.6%). Mean gestational age at first exposure was 20.7 (±5.7) weeks. Mean age at dental evaluation was 8.0 (±4.3) years for exposed and 10.4 (±5.1) years for controls (P <.01). Missing teeth, tooth size, shape, and color did not differ significantly between groups. There was no statistical difference in dental caries, facial abnormalities, or abnormalities of enamel or gingiva. There was no association between any chemotherapy agent or regimen and increased risk of dental abnormalities. Conclusions: Overall, there was no difference in dental abnormalities between groups. These negative findings may be because no one received chemotherapy prior to 14 weeks when formation of primary teeth was beginning. [ABSTRACT FROM AUTHOR]

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Breast cancer is the most common malignant neoplasm in women in the world, characterized by increasing morbidity and mortality. In clinics, breast cancer treatment is performed with surgical resection and adjuvant chemotherapy or radiotherapy. Surgery is quite invasive, takes a long time to recover, and carries a high risk of incomplete removal of the tumor tissue. Patients with other conditions, such as heart failure, could not tolerate surgery. Chemotherapy is one of the most commonly used treatments for cancer. Drug resistance (MDR) results in the unsatisfactory effectiveness of many chemotherapy drugs. Clinical trials use many potent chemotherapeutic drugs that have disadvantages such as lack of selectivity, poor bioavailability, and toxic effects on healthy cells. The combination of chemotherapy and photodynamic therapy (PDT) improved the therapeutic effects in multidrug-resistant cancer cells. Earlier studies have shown that phototherapy combined with chemotherapy can achieve an excellent anti-cancer effect at lower doses of drugs compared to those used conventionally. Nanomedicine-assisted chemo photodynamic therapy represents a promising therapeutic option for improved cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Spindle cell carcinoma (SpCC) is an unusual form of squamous cell carcinoma (SCC) and can sometimes present in the breast. Owing to the rarity of breast SpCC, few case studies are available nowadays and proper evidence is scarce. Case presentation: We herein report a 60-year-old female patient, who was referred to the surgery services after presenting with a right breast ulcerated mass. On physical examination, a 7x7 cm mass was found along with a 3 cm ulcer on the top of it. Both mammography and ultrasound showed a dense mass, and tru-cut and skin punch biopsies confirmed neoplastic spindle cells within the lesion. The patient underwent a right total mastectomy with sentinel lymph node biopsies with no further chemotherapy or radiotherapy. Conclusion: Owing to the heterogeneity of SpCC, there is no exact treatment protocol for this type of cancer, and mastectomy or conservative surgery can be performed in certain groups of patients depending on tumor size, stage, and lymph node involvement. Fortunately, promising medical and biological therapies might be of use in the near future. [ABSTRACT FROM AUTHOR]

Background: This study aimed to prospectively record changes to treatment for early breast cancer patients during the first wave of the COVID-19 pandemic in Australia. The purpose was to assess the impact on breast cancer outcomes and to determine the need for any mitigative actions. Methods: The study was conducted in the breast cancer unit of a tertiary referral hospital. Patients with early (non-metastatic) breast malignancy discussed in multidisciplinary team meetings between March and June 2020 were included. Patients were newly diagnosed, post-operative or post-neoadjuvant chemotherapy. Standard treatment was defined by Westmead Breast Cancer Institute protocols and any variations related to the pandemic were recorded. Results: In the study, 145 patients were included (median age 59 years). Pandemic-related changes to management were noted in 13 of 145 (9.0%) patients. Four patients experienced a delay to cancer treatments, four were not offered reconstructive/symmetrisation surgical procedures, three had altered radiotherapy protocols and two patients were not offered enrolment to a clinical trial. These impacts affected the groups presenting with new cancers (n=7/86, 8.1%), postoperative cases (n=4/25, 16.0%) and post-neoadjuvant chemotherapy cases presenting for surgical planning (n=2/34, 5.9%). Conclusion: Most patients (91.0%) received standard treatment during the first wave of the pandemic. The minor variations from institutional protocols observed in this study are unlikely to affect local control or survival in this patient cohort, but close follow-up is required. Quality of life may have been affected for four patients who had downgraded or delayed reconstructive procedures. [ABSTRACT FROM AUTHOR]

Background: The serotonin, copper, and ceruloplasmin markers are altered in various cancers, including breast cancer. It has been reported that these markers have the potential to be used in the study of cancer recurrence. The purpose of this study was to compare the levels of serotonin, copper and ceruloplasmin besides the routine breast cancer markers such as CEA and CA15-3 in the blood sample of patients with invasive ductal breast cancer, before and after chemotherapy. Methods: This study was performed on 30 patients with breast cancer. Blood samples were taken from the patients before and after chemotherapy. Necessary data including age, tumor grade and status of Her-2, ER, PR receptors were obtained from patient records. Serotonin, CEA and CA15-3 levels were measured by ELISA method. Ceruloplasmin and copper were measured by nephelometry and colorimetric methods, respectively. Results: Results showed a decrease in serotonin, ceruloplasmin, copper, CEA and CA15-3 after treatment but only the levels of serotonin and ceruloplasmin showed a steady decrease. No significant relationship was observed between tumor grade and ER-PR, Her-2 receptors. Conclusion: This study showed that chemotherapy resulted in steady decline in serotonin and ceruloplasmin levels but this decrease was not steady in levels of CA15-3 and CEA. Therefore, if our results are confirmed by further research, they can be considered as a viable alternative to routine markers in cancer recurrence after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: We investigated the prognostic and predictive roles of the hormone receptor (HRc) subtype in patients with ductal carcinoma in situ (DCIS). We focused on identifying the roles of the progesterone receptor (PR) independent of estrogen receptor (ER) status. Methods: Nationwide data of 12,508 female patients diagnosed with DCIS with a mean follow‐up period of 60.7 months were analyzed. HRc subtypes were classified as ER−/PR−, ER−/PR+, ER+/PR−, and ER+/PR+ based on ER and PR statuses. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The ER+/PR+ group showed better prognoses than the ER+/PR− and ER−/PR− groups in the patients who received tamoxifen therapy (p =.001 and p =.031, respectively). HRc subtype was an independent prognostic factor (p =.028). The tamoxifen therapy group showed better survival than the patients who did not receive tamoxifen, but only in the ER+/PR+ subgroup (p =.002). Tamoxifen therapy was an independent prognostic factor (HR, 0.619; 95% CI, 0.423 − 0.907; p =.014). PR status was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy (p <.001), and it remained a prognostic factor independent of ER status (HR, 0.576; 95% CI, 0.349 − 0.951; p =.031). Conclusion: The HRc subtype can be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Tamoxifen therapy can improve overall survival in the ER+/PR+ subtype. PR status has significant prognostic and predictive roles independent of ER status. Testing for the PR status in addition to the ER status is routinely recommended in patients with DCIS to determine the HRc subtype in clinical settings. Implications for Practice: The hormone receptor (HRc) subtype was an independent prognostic factor, and the estrogen receptor (ER)+/progesterone receptor (PR) + subtype showed a better survival in patients with ductal carcinoma in situ (DCIS) who received tamoxifen therapy. PR was an independent prognostic factor independent of ER, and PR was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy. The HRc subtype could be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Testing of PR status in addition to ER status is routinely recommended for patients with DCIS to determine the HRc subtype in clinical settings. This study investigated the prognostic and predictive roles of the hormone receptor subtype in patients with newly diagnosed ductal carcinoma in situ, focusing on the prognostic and predictive values of progesterone receptor status independent of estrogen receptor status. The prognostic effect of tamoxifen therapy was also investigated [ABSTRACT FROM AUTHOR]

Pregnancy-associated malignant diseases introduce multiple dilemmas to the multidisciplinary boards, related to both the oncological treatment as well as to obstetrical management. The most frequent oncological diseases diagnosed during pregnancy are breast cancer, oncohematological conditions, uterine cervix cancer and skin cancers. There are different clinical scenarios: interruption of the pregnancy and further use of the most appropriate oncological strategy; it is also possible to postpone the oncological treatment for the postpartum period with a watch-and-wait strategy until the foetus is mature and the delivery is planned. The third scenario includes concurrent treatment of both conditions: use of chemotherapy, radiotherapy and surgery during an ongoing pregnancy. Choosing among these scenarios is considering many factors, including type and stage of the malignant tumour, pregnancy term, desire and informed decision of the pregnant woman to keep or interrupt the pregnancy. The current review is focused on the basic principles of the oncological modalities (surgery, chemotherapy and radiotherapy) during pregnancy as well as their influence over the pregnant woman and the foetus, over the obstetrical management and the timing and mode of delivery, delivery anaesthesia, lactation and breastfeeding from the point of view of the evidence-based medicine. [ABSTRACT FROM AUTHOR]

Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accompanied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvastatin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes. [ABSTRACT FROM AUTHOR]

The efficacy of quantitative ultrasound (QUS) multi-parametric imaging in conjunction with unsupervised classification algorithms was investigated for the first time in characterizing intra-tumor regions to predict breast tumor response to chemotherapy before the start of treatment. QUS multi-parametric images of breast tumors were generated using the ultrasound radiofrequency data acquired from 181 patients diagnosed with locally advanced breast cancer and planned for neo-adjuvant chemotherapy followed by surgery. A hidden Markov random field (HMRF) expectation maximization (EM) algorithm was applied to identify distinct intra-tumor regions on QUS multi-parametric images. Several features were extracted from the segmented intra-tumor regions and tumor margin on different parametric images. A multi-step feature selection procedure was applied to construct a QUS biomarker consisting of four features for response prediction. Evaluation results on an independent test set indicated that the developed biomarker coupled with a decision tree model with adaptive boosting (AdaBoost) as the classifier could predict the treatment response of patient at pre-treatment with an accuracy of 85.4% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89. In comparison, the biomarkers consisted of the features derived from the entire tumor core (without consideration of the intra-tumor regions), and the entire tumor core and the tumor margin could predict the treatment response of patients with an accuracy of 74.5% and 76.4%, and an AUC of 0.79 and 0.76, respectively. Standard clinical features could predict the therapy response with an accuracy of 69.1% and an AUC of 0.6. Long-term survival analyses indicated that the patients predicted by the developed model as responders had a significantly better survival compared to the non-responders. Similar findings were observed for the two response cohorts identified at post-treatment based on standard clinical and pathological criteria. The results obtained in this study demonstrated the potential of QUS multi-parametric imaging integrated with unsupervised learning methods in identifying distinct intra-tumor regions in breast cancer to characterize its responsiveness to chemotherapy prior to the start of treatment. [ABSTRACT FROM AUTHOR]

Secretory carcinoma of the breast (SCB) is a rather rare entity of invasive breast cancer, the clinicopathologic characteristics and survival outcomes remain to be elaborated. A retrospective review was conducted in SEER database. A total of 190 SCB patients identified in SEER were eligible for inclusion in the analysis. Median age at diagnosis was 56 years (range 2–96 years). Both sexes and bilateral breast could be affected. Intriguingly, the incidence of SCB tended towards to decreasing in recent decades. Small tumor burden was observed with a mean tumor size of 2.13 cm. In a subgroup with sufficient details, positive staining of estrogen receptor (ER) and progesterone receptor (PR) was 58% and 40%, respectively. The vast majority of patients were of well to moderate differentiation (86.86%) and negative regional lymph nodes involvement (70.71%). Nearly half of the patients took radiotherapy and chemotherapy. Seniors were inclined to have an inferior breast cancer specific survival (BCSS) than their younger counterparts (P = 0.018). Patients underwent breast conserving surgery (BCS) and radiotherapy had much better BCSS than its mastectomy counterparts (P = 0.014). Collectively, SCB is a clinical indolent invasive breast cancer with excellent prognosis. BCS in conjunction with radiotherapy would be a rational alternative for this distinct entity. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background/Aim: Axillary reverse mapping (ARM) aims to identify and preserve arm drainage in order to prevent lymphedema following axillary lymph node dissection. Oncological-safety and feasibility are still debated, especially in patients with locally-advanced breast cancer (LABC). We report the first case of the AXMAP 1.0 study performed in our Institution. Patients and Methods: A 52-year-old patient with a triple-negative LABC and partial response to neoadjuvant chemotherapy underwent axillary lymph-node dissection using fluorescence ARM. Results: Two lymph-nodes draining the ipsilateral upper arm were identified and were not preserved due to suspicion of malignancy. Pathological examination confirmed the presence of malignancy in both lymph nodes. Conclusion: Further studies should be designed in order to validate the oncological safety of this technique, especially in patients with LABC requiring neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background/Aim: Oncotype DX recurrence score (RS) for breast cancer is a useful tool for determining chemotherapy indication but it is expensive and time-consuming. We determined whether four immuno-histochemical markers, namely human epidermal growth factor 2 (HER2), estrogen receptor (ER), progesterone receptor (PgR), and Ki-67, are predictive of an RS ≥26 in Japanese patients. Patients and Methods: The study included 95 Japanese patients evaluated for RS. A predictive model was created using logistic regression analysis. Results: The discriminant function was calculated as follows: p=1/{1+exp [-(4.611+1.2342×HER2-0.0813×ER-0.0489 ×PgR+0.0857×Ki67)]}. Using a probability of 0.5 as the cutoff, the accuracy, sensitivity, specificity, positive predictive and negative predictive values were 90.5%, 72.2%, 94.8%, 76.4% and 93.5%, respectively. Conclusion: The model had a high negative predictive value in predicting RS ≥26 in Japanese patients, indicating that Oncotype DX testing may be omitted in patients with a negative result according to the predictive model. [ABSTRACT FROM AUTHOR]

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt "healthier dietary patterns" during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity. [ABSTRACT FROM AUTHOR]

Perineural invasion (PNI) is a pathologic finding observed across a spectrum of solid tumors, typically with adverse prognostic implications. Little is known about how the presence of PNI influences locoregional recurrence (LRR) among breast cancers. We evaluated the association between PNI and LRR among an unselected, broadly representative cohort of breast cancer patients, and among a propensity-score matched cohort. We ascertained breast cancer patients seen at our institution from 2008 to 2019 for whom PNI status and salient clinicopathologic features were available. Fine-Gray regression models were constructed to evaluate the association between PNI and LRR, accounting for age, tumor size, nodal involvement, estrogen receptor (ER), progesterone receptor (PR), HER2 status, histologic tumor grade, presence of lymphovascular invasion (LVI), and receipt of chemotherapy and/or radiation. Analyses were then refined by comparing PNI-positive patients to a PNI-negative cohort defined by propensity score matching. Among 8864 invasive breast cancers, 1384 (15.6%) were noted to harbor PNI. At a median follow-up of 6.3 years, 428 locoregional recurrence events were observed yielding a 7-year LRR of 7.1% (95% CI 5.5–9.1) for those with PNI and 4.7% (95% CI 4.2–5.3; p = 0.01) for those without. On univariate analysis throughout the entire cohort, presence of PNI was significantly associated with an increased risk of LRR (HR 1.39, 95% CI 1.08–1.78, p < 0.01). Accounting for differences in salient clinicopathologic and treatment parameters by multivariable Fine-Gray regression modeling, the association between PNI and LRR was potentiated (HR 1.57, 95% CI 1.2–2.07, p = 0.001). We further conducted propensity score matching to balance clinicopathologic parameters and treatments between the two groups (PNI vs not), again showing a similar significant association between PNI and LRR (HR 1.46, 95% CI 1.03–2.08, p = 0.034). PNI is significantly associated with LRR following the definitive treatment of invasive breast cancer. The excess risk conferred by PNI is similar in magnitude to that observed with LVI, or by ER/PR negativity. Breast cancer prognostication and therapeutic decision-making should consider the presence of PNI among other salient risk factors. Larger studies among more uniform breast cancer presentations may elucidate the extent to which these findings apply across breast cancer subtypes and stages. [ABSTRACT FROM AUTHOR]

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients. [ABSTRACT FROM AUTHOR]

Survival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m2 to 23.87 kg/m2, p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer. Methods: We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events. Results: Four randomized controlled trials (N = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, P < 0.001). Three randomized controlled trials (N = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, P = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, P = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, P = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, P = 0.008). Conclusions: First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia. [ABSTRACT FROM AUTHOR]

Obesity is a known factor increasing the risk of developing breast cancer and reducing disease free survival. In addition to these well-documented effects, recent studies have shown that obesity is also affecting response to chemotherapy. Among the multiple dysregulations associated with obesity, increased level of the apelin adipokine has been recently shown to be directly involved in the association between obesity and increased breast cancer progression. In this study, we analyzed in a retrospective cohort of 62 breast cancer patients the impact of obesity and tumoral apelin expression on response to neoadjuvant chemotherapy. In the multivariate logistic regression, obesity and high tumoral apelin expression were associated with a reduced response to NAC in our cohort. However, obesity and high tumoral apelin expression were not correlated, suggesting that those two parameters could be independently associated with reduced NAC response. These findings should be confirmed in independent cohorts. [ABSTRACT FROM AUTHOR]

The application of nanomedicine represents an innovative approach for the treatment in the modern field of cancer chemotherapy. In the present research work, tamoxifen citrate loaded nanolipid vesicles were prepared conjugated with phosphoethanolamine as the linker molecule, and the specific antibody was tagged with the linker molecule on the bilayer surface of the vesicles. The main objective of this study is to determine the efficacy and biological behavior of antibody conjugated nanoliposome in breast cancer cell lines. Percentage of drug loading and loading efficiency was done and their results were compared to theoretical drug loading. The average diameter of those vesicles was within the 100 nm range, which is revealed in FESEM and TEM images and their lamellarity was observed in cryo-TEM images. The hydrodynamic diameter was done by particle size analysis and the surface charge was determined by the zeta potential parameter. Predominant cellular uptake was observed for antibody conjugated nanolipid vesicles in MCF-7 and MDA-MB-453 human breast cancer cell lines. A cellular apoptosis assay was conducted by flow cytometer (FACS). All experimental data would be more beneficial for the treatment of breast cancer chemotherapy. Further studies are warranted to investigate the efficacy and safety of antibody conjugated nanolipid vesicles in vivo for breast cancer animal model.

Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes. Clinical Trial Registration: Trial was retrospectively registered to the Australia New Zealand Clinical Trial Registry (ANZCTR). ACTRN12620000832976, 21 Aug 2020, https://www.anzctr.org.au/ACTRN12620000832976.aspx. [ABSTRACT FROM AUTHOR]

The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage < 3 in Spain between 2008 and 2013 was begun and then followed-up until 2017/2018. Data on patient and tumour characteristics were obtained from medical records, as well as their first line treatment. First line treatments were classified in three categories, according on whether they included the main St Gallen-2013 recommendations, more than those recommended or less than those recommended. Multinomial logistic regression models were carried out to identify factors associated with this classification and Weibull regression models were used to find out the relationship between this classification and survival. About half of the patients were treated according to St Gallen recommendations; 21% were treated over what was recommended and 33% received less treatment than recommended. Factors associated with treatment over the recommendations were stage II (relative risk ratio [RRR] = 4.2, 2.9–5.9), cancer positive to either progesterone (RRR = 8.1, 4.4–14.9) or oestrogen receptors (RRR = 5.7, 3.0–11.0). Instead, factors associated with lower probability of treatment over the recommendations were age (RRR = 0.7 each 10 years, 0.6–0.8), poor differentiation (RRR = 0.09, 0.04–0.19), HER2 positive (RRR = 0.46, 0.26–0.81) and triple negative cancer (RRR = 0.03, 0.01–0.11). Patients treated less than what was recommended in St Gallen had cancers in stage 0 (RRR = 21.6, 7.2–64.5), poorly differentiated (RRR = 1.9, 1.2–2.9), HER2 positive (RRR = 3.4, 2.4–4.9) and luminal B-like subtype (RRR = 3.6, 2.6–5.1). Women over 65 years old had a higher probability of being treated less than what was recommended if they had luminal B-like, HER2 or triple negative cancer. Treatment over St Gallen was associated with younger women and less severe cancers, while treatment under St Gallen was associated with older women, more severe cancers and cancers expressing HER2 receptors. [ABSTRACT FROM AUTHOR]

Carcinoma arising in ectopic breast tissue is a rare entity, especially in males, in whom the diagnosis is often delayed due to a low index of suspicion. Conventional imaging techniques fail to characterize the tumor, adding further to the diagnostic dilemma. We report the first case in our knowledge of an extramammary primary breast carcinoma arising in the inguinal region in a male. Our patient, a 69-year-old male, presented with a swelling in the left inguinal region, which was excised and diagnosed as luminal A type invasive ductal carcinoma. He received adjuvant external beam radiotherapy (50 Gy administered in 25 fractions) and tamoxifen. A follow-up examination performed 6 months after the completion of the last dose of radiotherapy showed no residual disease. The modalities of treatment for such tumors have been discussed, with emphasis on surgery and radiotherapy, given the aggressive nature of the disease. [ABSTRACT FROM AUTHOR]