Breast Cancer Recurrence Research Articles

U.S. payer budget impact of using an AI-augmented cancer risk discrimination digital histopathology platform to identify high-risk of recurrence in women with early-stage invasive breast cancer

Aims Use of gene expression signatures to predict adjuvant chemotherapy benefit in women with early-stage breast cancer is increasing. However, high cost, limited access, and eligibility for these tests results in the adoption of less precise assessment approaches. This study evaluates the cost impact of PreciseDx Breast (PDxBr), an AI-augmented histopathology platform that assesses the 6-year risk of recurrence in early-stage invasive breast cancer patients to help improve informed use of adjuvant chemotherapy. Materials and methods A decision-tree Markov model was developed to compare the costs of treatment guided by standard of care (SOC) risk assessment (i.e. clinical diagnostic workup with or without Oncotype DX) versus PDxBr with SOC in a hypothetical cohort of U.S. women with early-stage invasive breast cancer. A commercial payer perspective compares costs of testing, adjuvant therapy, recurrence, adverse events, surveillance, and end-of-life care. Results PDxBr use in prognostic evaluation resulted in savings of $4 million (M) in year one compared to current SOC in 1 M females members. Over 6-years, savings increased to $12.5 M. The per-treated patient costs in year one amounted to $19.5 thousand (K) for SOC and $16.9K for PDxBr. Limitations For simplicity, recurrence was not specified. We performed scenario analyses to account for variations in rates for local, regional, and distant recurrence. Second, a recurrent patient incurs the total cost of treated recurrence in the first year and goes back to remission or death. Third, CDK4/6i treatment is only incorporated in the recurrence costs but not in the first line of treatment for early-stage breast cancer due to limited data. Conclusions Sensitivity analyses demonstrated robust overall savings to changes in all variables in the model. The use of PDxBr to assess breast cancer recurrence risk has the potential to fill gaps in care and reduce costs when gene expression signatures are not available.

Impact of Hyperparameter Optimization to Enhance Machine Learning Performance: A Case Study on Breast Cancer Recurrence Prediction

Accurate and early prediction of breast cancer recurrence is crucial to guide medical decisions and treatment success. Machine learning (ML) has shown promise in this domain. However, its effectiveness critically depends on proper hyperparameter setting, a step that is not always performed systematically in the development of ML models. In this study, we aimed to highlight the impact that this process has on the final performance of ML models through a real-world case study by predicting the five-year recurrence of breast cancer patients. We compared the performance of five ML algorithms (Logistic Regression, Decision Tree, Gradient Boosting, eXtreme Gradient Boost, and Deep Neural Network) before and after optimizing their hyperparameters. Simpler algorithms showed better performance using the default hyperparameters. However, after the optimization process, the more complex algorithms demonstrated superior performance. The AUCs obtained before and after adjustment were 0.7 vs. 0.84 for XGB, 0.64 vs. 0.75 for DNN, 0.7 vs. 0.8 for GB, 0.62 vs. 0.7 for DT, and 0.77 vs. 0.72 for LR. The results underscore the critical importance of hyperparameter selection in the development of ML algorithms for the prediction of cancer recurrence. Neglecting this step can undermine the potential of more powerful algorithms and lead to the choice of suboptimal models.

Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Young Women with Early-Stage Breast Cancer Treated with Upfront Surgery: Overview of Oncological Outcomes.

Background: Breast cancer in young women aged < 40 years is rare and often aggressive with less favorable survival rates. The lack of systematic screening, later stage at diagnosis, and a more aggressive disease biology may all contribute to their poor prognosis. Data on the best management remain conflicting, especially those regarding surgical management, either breast-conserving or mastectomy. To our knowledge, there are limited studies surrounding the treatment of young women with early breast cancer, and this analysis evaluated the oncological outcomes for those patients who underwent surgery upfront. Methods: We conducted a retrospective study including 130 young women with early breast cancer from a total of 373 consecutive patients treated with upfront surgery between January 2016 and December 2021 at our institution. Local recurrence-free survival (LR-FS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: The median follow-up was 61.1 months (range, 25-95). A total of 92 (70.8%) patients underwent breast-conserving surgery, while 38 (29.2%) patients underwent conservative mastectomy with immediate implant breast reconstruction. In total, 8 of 130 patients (6.2%) developed a local recurrence in the treated breast, an7 (5.4%) patients presented distant metastasis. Overall, two (1.6%) patients died due to breast cancer recurrence. Conclusions: The results of our study interestingly support breast-conserving surgery in young patients with early-stage breast cancer. While appropriate breast-conserving surgery can achieve favorable oncological outcomes and can always be considered a valid alternative to conservative mastectomy in upfront surgery, a younger age at diagnosis should never be used alone to choose the type of surgery.

Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up.

Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.

1211 Patterns of Recurrences After Mastectomy for Invasive Breast Cancer and DCIS Followed by Immediate Breast Reconstruction: 13-Year Follow-Up from a Single institution

Abstract Aim A retrospective review was conducted at a single centre to analyse the patterns of recurrence in IBR. Method Between January 2009 and December 2021, 347 patients who had IBR for either invasive (244) or DCIS (125), were analysed retrospectively. The study included patients who received implants without ADM (10.8%), ADM with +implant (69%), Latissimus Dorsi flap +/- implant (18.1%), and deep inferior epigastric perforator-free flaps (2.5%). Results During the study period, 29 patients developed recurrence over a median period of 74 months (ranging from 24 to 125 months). Two patients had local cancer recurrence only (0.5%), 5 patients had local recurrence associated with distant or regional metastasis, (1.4%) and 19 cases with distal metastasis were identified (8.3%). The study found an overall survival rate of 96.4% and a disease-free survival rate of 91.7%. The most familiar sites of recurrence in breast cancer are distal recurrence, (Bone being the most common site), followed by local recurrence. Discussion This rate is in line with the expected range, assuming a standard of recurrence of 1% per year. Nevertheless, it is crucial to acknowledge the possibility of selection bias, as patients with advanced diseases and significant comorbidities may not have been offered IBR. Conclusions Based on the findings of the study, it can be inferred that mastectomy with (IBR) is a safe option for mastectomy.

P-317 Risk of endometrial polyps and hyperplasia after tamoxifen treatment in women with breast cancer: a population-based study in Taiwan

Abstract Study question This study aimed to examine the association between tamoxifen treatment and incident risks of uterine disease among breast cancer patients in Taiwan. Summary answer We found tamoxifen treatment group may have greater risk of endometrial polyps and hyperplasia than unexposured group after adjusting for age and body mass index. What is known already In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) breast cancer treatment trail reported that the women continue tamoxifen up to 10 years, compared with 5 years may reduce breast cancer recurrence and mortality rate. However, tamoxifen use has been reported to be associated with the cumulative risk of subsequently endometrial cancer during 5–14 years was 3.1%. Specifically, several Western studies have showed that the high incidence of endometrial cancer in breast cancer survivors with tamoxifen treatment. Study design, size, duration We conducted a retrospective cohort study using population-based data from Taiwan Cancer Registry and the National Health Insurance Research Database (NHIRD), and the National Population Registry Data set from 2011 to 2020. Participants/materials, setting, methods A total 138,934 newly diagnosed breast cancer female patients with age greater than 18 years old were included. We further used a 1-to-1 propensity score matching to generate comparable exposure and un-exposure groups. Cox proportional hazard regression models were used to examine the research question. All statistical analysis was performed using SAS version 9.4, and p-values &amp;lt; 0.05 were considered statistically significant Main results and the role of chance Incidence rate ratio (IRR) to compare incidence rate of uterine disease between tamoxifen treatment groups and unexposed group, adjusting for age and BMI. Our results showed that IRR were 1.36, 0.33, 3.73, 0.63, endometrial polyps, endometrial carcinoma, endometrial hyperplasia and uterine carcinosarcoma, respectively. This study found possible correlations between tamoxifen exposure with endometrial polyps and hyperplasia among breast cancer. During the 10-year study period, tamoxifen group did not significantly increase the risk of endometrial cancer in breast cancer survivors at aged 40 and over. Limitations, reasons for caution Our cohort study with 10-year period is its short study period, Tamoxifen group did not significantly increase the risk of endometrial cancer. Wider implications of the findings This cohort study found higher endometrial polyps and hyperplasia incidence rates among women with breast cancer who received tamoxifen women than those not treated with tamoxifen. Results of this study suggest that clinicians should consider the risk of uterine disease among tamoxifen use and counsel patients accordingly. Trial registration number KMUHIRB-G(II)20200217

Use of ultrasound imaging Omics in predicting molecular typing and assessing the risk of postoperative recurrence in breast cancer

BackgroundThe aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer.MethodsA retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves.ResultsIn the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability.ConclusionThe use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.

EV-miRNAs from breast cancer patients of plasma as potential prognostic biomarkers of disease recurrence

BackgroundExtracellular vesicles (EVs), ubiquitously released by blood cells, facilitate intercellular communication. In cancer, tumor-derived EVs profoundly affect the microenvironment, promoting tumor progression and raising the risk of recurrence. These EVs contain miRNAs (EV-miRNAs), promising cancer biomarkers. Characterizing plasma EVs and identifying EV-miRNAs associated with breast cancer recurrence are crucial aspects of cancer research since they allow us to discover new biomarkers that are effective for understanding tumor biology and for being used for early detection, disease monitoring, or approaches to personalized medicine. This study aimed to characterize plasma EVs in breast cancer (BC) patients and identify EV-miRNAs associated with BC recurrence. MethodsThis retrospective observational study included 24 BC patients divided into recurrence (n= 11) and non-recurrence (n= 13) groups. Plasma EVs were isolated and characterized. Total RNA from EVs was analyzed for miRNA expression using NanoString's nCounter® miRNA Expression Assays panel. MicroRNA target prediction used mirDIP, and pathway interactions were assessed via Reactome. ResultsA stronger presence of circulating EVs was found to be linked with a less favorable prognosis (p = 0.0062). We discovered a distinct signature of EV-miRNAs, notably including miR-19a-3p and miR-130b-3p, which are significantly associated with breast cancer recurrence. Furthermore, miR-19a-3p and miR-130b-3p were implicated in the regulation of PTEN and MDM4, potentially contributing to breast cancer progression.A notable association emerged, indicating a high concentration of circulating EVs predicts poor prognosis (p = 0.0062). Our study found a distinct EV-miRNA signature involving miR-19a-3p and miR-130b-3p, strongly associated with disease recurrence. We also presented compelling evidence for their regulatory roles in PTEN and MDM4 genes, contributing to BC development. ConclusionThis study revealed that increased plasma EV concentration is associated with BC recurrence. The prognostic significance of EVs is closely tied to the unique expression profiles of miR-19a-3p and miR-130b-3p. These findings underscore the potential of EV-associated miRNAs as valuable indicators for BC recurrence, opening new avenues for diagnosis and treatment exploration.

Adjuvant and Neoadjuvant Therapy for Breast Cancer: A Systematic Review.

Breast cancer (BC) is the most frequent type of cancer among women. The neoadjuvant therapy was administered before surgery, and the adjuvant therapy was administered post-surgery. The goal of this systematic review is to study the effects of adjuvant and neoadjuvant BC therapy on patient outcomes and mortality. In July 2023, systematic searches were conducted through the Cochrane Library, Web of Sciences, Google Scholar, EMBASE, and PubMed databases. The search method focused on studies that included all patients with BC stages 1, 2, and 3 and excluded studies that included patients with metastatic and recurrent BC. The risk of bias in the included studies was evaluated using the Cochrane risk of bias technique. Throughout our search, 27 relevant studies with 161,552 patients were discovered. Anti-human epidermal growth factor 2 therapy (trastuzumab, pertuzumab), chemotherapy (anthracycline), endocrine therapy (tamoxifen, aromatase inhibitor), and bisphosphonates were recommended treatments for BC patients. Choices for radiotherapy included whole breast, partial breast, tumor bed boost, regional nodes, and chest wall choices after breast-conserving surgery. We discover that while the majority of treatments reduced the mortality or recurrence rates of BC, anthracycline, chemotherapy, and radiation led to an overall rise in non-BC deaths. The systemic assessment discovered several variables that impact a patient's quality of life. Based on these advantages and disadvantages, various treatment options for patients and recommendations for groups of women are made.

Salvage Breast-Conserving Surgery and Reirradiation With Intraoperative Electrons for Recurrent Breast Cancer: A Multicentric Study on Behalf of Italian Association of Radiotherapy and Clinical Oncology (AIRO)

AimIntraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. Materials and MethodsA database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) ResultsFrom 2002 to 2015, 109 patients underwent the conservative retreatment.The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. Conclusion2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer.

Assessing risk of recurrence for nonmetastatic triple-negative breast cancer (TNBC) is a key determinant of therapeutic strategy. The best predictor of recurrence risk is failure to achieve a pathologic complete response after preoperative chemotherapy, but it imperfectly correlates with the definitive end points of relapse-free and overall survival (OS). The inability to accurately predict recurrence has led to increasingly toxic treatment regimens for patients with early-stage TNBC. Better assays for recurrence risk are needed to tailor aggressive therapy for patients who need it and avoid overtreatment and unnecessary toxicity for those at low risk. The purpose of this study was to determine if patient-derived xenograft (PDX) engraftment of newly diagnosed breast tumors can serve as an accurate predictor of recurrence and death from breast cancer. This study was a blinded noninterventional trial comprising 80 patients with newly diagnosed, nonmetastatic, estrogen receptor (ER)-negative or ER-low breast cancer. PDX engraftment was strongly associated with relapse in 1 year: 8 of 18 (44.4%) patients whose tumors engrafted relapsed versus 1 of 62 (1.6%) patients whose tumors did not engraft (P < .0001). Patients whose tumors engrafted had a hazard ratio (HR) for relapse of 17.5. HRs for OS and breast cancer-specific survival in PDX+ patients were 21.1 and 39.5, respectively. We report that the ability of a tumor to engraft as a PDX predicts early recurrence by serving as a functional readout of aggressiveness and prospectively identifies the most devastating tumors. This provides new opportunity to develop surrogate assays, such as biomarkers of engraftment, which will extend the clinical feasibility of this finding.

ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer

There are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13). In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

The Effect of C-Reactive Protein/Lymphocyte Ratio (CLR) on PFS in Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitors: A Novel Biomarker.

Hormone positive breast cancer is a tumor with high mortality. Combining antihormonal therapy with cyclin dependent kinase 4/6 inhibitors (CDK4/6i) has resulted in longer survival. The effect of inflammatory parameters such as c-reactive protein and c-reactive protein/lymphocyte ratio (CLR) on efficacy and survival in CDK4/6i treatment is unknown. In our study, we aimed to investigate the role of CLR and some parameters in predicting progression-free survival (PFS) with CDK4/6i. This retrospective cohort study included 78 patients with denovo and recurrent metastatic breast cancer treated with CDK4/6i. Cut off values for the prediction of mortality by various numerical parameter scores were performed by ROC Curve analysis. The effect of clinical variables, inflammatory and histopathological parameters on survival was analyzed by Kaplan-Meier method. Neutrophil/lymphocyte ratio (NLR) and CLR were statistically significant in predicting mortality (p < 0.05). Ki67 and CLR were correlated with PFS. Age and CLR were correlated with OS (p < 0.05). CLR was statistically significant for both PFS (p = 0.022) and OS (p = 0.006). In patients with metastatic hormone-positive breast cancer using CDK4/6i, low CLR and low Ki67 were correlated with longer PFS duration.

Systemic Treatment After Locoregional Recurrence in Breast Cancer: A Review

Locoregional recurrence (LRR) in breast cancer poses significant challenges due to its association with biologically resistant disease and a high likelihood of concurrent occult systemic disease. Despite advancements in local and systemic therapies, LRR affects a substantial percentage of patients, leading to poorer prognosis compared to those with primary breast cancer. Therefore, a comprehensive review of systemic treatment strategies following LRR is warranted to address the gaps in our understanding and improve patient outcomes. This review explored factors influencing the prognosis of breast cancer LRR. In particular, we evaluated the benefits of systemic treatment options post-resection and proposed an optimal treatment algorithm.

Clinical and Pathological Predictors of Recurrent Breast Cancer

Objectives: Recurrence of breast cancer is common. There are reported risk factors for recurrence which are patient age, tumor size, tumor grade, (lymph vascular invasion (LVI), extensive intraductal component (EIC), and margin status. Nodal involvement also contributes to the recurrence rate as well as hormonal status, and if the patient receives neoadjuvant/adjuvant therapy or not. The aim of this study is to look for the clinical and pathological predictors of patients who have recurrent breast cancer after surgical treatment. Methods: We conducted a retrospective cohort study at one center (Royal hospital) between 2010 to 2020 for patients who were treated surgically for nonmetastatic breast cancer. We collected the clinical which was mainly the age at the diagnosis and pathological predictors (final histopathology report of the surgical specimen) from the medical records system of the hospital after obtaining the ethical approval. Total sample size was 270 Omani patients. The primary endpoint was the time to locoregional recurrence or systemic recurrence as the first event. A multivariate analysis of the predictors was carried and a P-value of &lt; 0.05 was considered statistically significant with 95% CI. Results: Out of 270 patients with breast cancer who were surgically treated, 113 had recurrence and 157 had no recurrence. There were 104 patients with recurrence have invasive ductal carcinoma (IDC) and 9 patients with high-grade ductal carcinoma in situ (DCIS). The Mean age of patients with recurrence was 44.0 while in patients without recurrence was 48.3. The difference in age between the two groups is not statistically significant in predicting the recurrence (p = 0.816). ER, LVI, EIC, nodal involvement, grade, margin, and type of tumor were the significant predictors of recurrence by bivariate analysis. However, High grade (Hazard ratio (HR) = 3.823, 95% CI: 1.104-13.240; p = 0.034), EIC (HR = 17.407, 95% CI: 1.538-196.999; p = 0.021), and nodal involvement (HR = 2.314, 95% CI: 1.123-4.767; p = 0.023) remain the significant predictors for recurrent breast cancer in the multivariate Cox regression analysis. By using Kaplan-Meier, the median survival time was 132 months and the recurrence-free survival at two years was 88.0% (The recurrence rate = 12.0%). Conclusions: High grade, extensive intraductal component, and nodal involvement are significant predictors for breast cancer recurrence. The recurrencefree survival at 2 years is 88.0%. Our recommendation is a close follow-up for patients with these predictors.

Mediterranean diet: Fighting breast cancer naturally: A review.

The effects and mechanisms of the Mediterranean diet (MD) on the incidence, recurrence, and prevention of breast cancer (BC) have been extensively investigated since the 1990s. Recent years have witnessed significant advancements in understanding the relationship between the components of the MD and BC, particularly in terms of their role and adherence. This comprehensive review focuses on several key aspects: the influence of the adherence of MD in cohort studies conducted across different regions on BC, the effects and mechanisms of individual component or main components as well as the supplementation of vitamins, drugs, exercise, and other factors of MD on BC; the variations in the impact of the MD on premenopausal and postmenopausal women, as well as different types in BC cases; the possible mechanisms underlying the development, recurrence, and prevention of BC in relation to the MD; and the interaction effects of individual genetic polymorphisms with the MD. Based on current research findings, this review highlights the key issues and identifies future research directions in investigating the relationship between the MD and BC. Furthermore, it suggests that healthy women of various ages and BC patients should adhere to MD in order to prevent BC or improve the prognosis.

Mesenchymal Stem Cell-Secreted Exosomes and Soluble Signals Regulate Breast Cancer Metastatic Dormancy: Current Progress and Future Outlook.

Breast cancer is most common in women, and in most cases there is no evidence of spread and the primary tumor is removed, resulting in a 'cure'. However, in 10% to 30% of these women, distant metastases recur after years to decades. This is due to breast cancer cells disseminating to distant organs and lying quiescent. This is called metastatic dormancy. Dormant cells are generally resistant to chemotherapy, hormone therapy and immunotherapy as they are non-cycling and receive survival signals from their microenvironment. In this state, they are clinically irrelevant. However, risk factors, including aging and inflammation can awaken dormant cells and cause breast cancer recurrences, which may happen even more than ten years after the primary tumor removal. How these breast cancer cells remain in dormancy is being unraveled. A key element appears to be the mesenchymal stem cells in the bone marrow that have been shown to promote breast cancer metastatic dormancy in recent studies. Indirect co-culture, direct co-culture and exosome extraction were conducted to investigate the modes of signal operation. Multiple signaling molecules act in this process including both protein factors and microRNAs. We integrate these studies to summarize current findings and gaps in the field and suggest future research directions for this field.

Efficacy and Safety of BP02 (Trastuzumab Biosimilar) in HER2-Positive Metastatic Breast Cancer: A Multicenter Phase III Study.

Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02,a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as atrastuzumab biosimilar. The objective of this study was to evaluate the equivalence of BP02 with reference trastuzumab (RT: Herceptin®-EU) in patients withHER2-positive metastatic breast cancer. This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75mg/m2 on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ±13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively. BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks. CTRI Number: CTRI/2020/04/024456.

Recurrence of breast cancer after reconstruction with macro-textured silicone breast implants: A retrospective cohort study.

Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, we investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients. We conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between January 1st 2000 and December 31st 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data was accounted for by multiple imputation by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard Ratios (HRs) were estimated using multivariable Cox proportional hazard models. Of the 4,695 women who were eligible for inclusion, 2,393 had undergone mastectomy. Of these women, 1,187 (25%) had received breast reconstruction with a macro-textured SBI. Mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors (HR 1.27 [95% CI 0.93 - 1.72] and HR 0.94 [95% CI 0.74 - 1.20], respectively). Sensitivity analysis in complete cases of patients and varies subgroup analyses yielded similar results. Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction.