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Background: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups. Methods: We analyzed the 2010–2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS." Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%. Results: Overall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94–0.97) or PR% (AOR=0.98, 95% CI 0.96–0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04–1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29–0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41–0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01–1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS. Conclusions: Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%--30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody--drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2- positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC. [ABSTRACT FROM AUTHOR]

Background: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC). Objective: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival. Design: Cohort study. Methods: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding. Results: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P <.05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates. Conclusion: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients. Plain Language Summary: Breast-preserving treatment leads to higher 10-year survival in early-stage breast cancer This study compared the long-term survival outcomes of breast-conserving therapy (BCT) and mastectomy for early-stage breast cancer. Analyzing data from over 3400 women diagnosed in 2004, researchers found that BCT recipients had higher 10-year overall and breast cancer-specific survival rates compared with mastectomy recipients. Adjusted models showed a 22% higher risk of all-cause death [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to identify preoperative factors that may predict positive resection margins in patients undergoing breast-conserving surgery for early-stage breast cancer. By retrospectively analyzing patient records from 2009 to 2017, the study investigates preoperative factors associated with positive resection margins. The findings indicate that neoadjuvant chemotherapy and the presence of ductal carcinoma in situ are significantly associated with positive resection margins. These results underscore the importance of these preoperative factors in surgical planning and management, potentially leading to improved outcomes for breast cancer patients. The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher's exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. Methods: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Results: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9–98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Conclusion: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. ClinicalTrials.gov Registration: NCT03892655. [ABSTRACT FROM AUTHOR]

Background: Anthracycline- and taxane-based chemotherapy regimens are established treatments for human epidermal growth factor receptor (HER)2-negative early-stage breast cancer with high risk of recurrence. This study examined the prevalence of these chemotherapy regimens as perioperative therapy, the patterns of retreatment, and factors influencing prescription choices in Japan. Methods: This observational cohort study focused on high-risk early-stage breast cancer patients not undergoing anti-HER2 therapy, utilizing data from a hospital-based claims database in Japan spanning from April 2008 to September 2021. Results: Of 42,636 high-risk patients who underwent breast cancer surgery, 32,133 (75.4%) were categorized as having luminal-type (received endocrine therapy) and 10,503 (24.6%) as having triple-negative cancer (not receiving any endocrine therapies). Most patients (98.7%) with luminal-type breast cancer received perioperative therapy, and 40.3% of those received anthracycline/taxane. In the triple-negative group, 57.0% of all patients received perioperative therapy and of those, 93.4% received anthracycline/taxane. Being over 40 years old, having an early stage (clinical stage ≤ II), and receiving treatment in non-specialized facilities were associated with less use of anthracycline/taxane in the luminal-type group. For the triple-negative group, associated factors with less use of anthracycline/taxane included being over 60 years old, treatment in small hospital (capacity < 200 beds), and treatment in non-specialized facilities. Conclusions: Approximately half the patients in both the luminal-type and triple-negative groups were prescribed anthracycline and/or taxane for perioperative chemotherapy. The choice was associated with patient age, cancer stage, and the scale and specialization of the treatment facilities. This study sheds light on the current state of breast cancer treatment practices in Japan. [ABSTRACT FROM AUTHOR]

Online interventions that elicit kindness may enhance well-being. We tested the efficacy of three kindness interventions among breast cancer survivors. Participants (N = 137, M age = 62.65 years) were randomized to perform acts of kindness for others, acts of kindness for self, self-kindness meditation, or a daily-activities-writing control and completed three activities each week for 4 weeks. Primary (well-being, depressive symptoms) and secondary outcomes (social support, self-kindness) were assessed pre- and post-intervention. No differences emerged in the primary outcomes. However, relative to controls, participants in the acts of kindness to others condition reported greater increases in social support, and participants in the self-kindness meditation condition reported greater decreases in self-kindness. Among breast cancer survivors, performing prosocial acts may enhance feelings of social support. The two self-kindness conditions yielded either null or detrimental effects, suggesting that further research is needed on best practices for conducting self-focused kindness interventions.

Abstract Introduction Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil’s ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. Methods We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Results Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9–98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Conclusion Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst’s role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. ClinicalTrials.gov Registration NCT03892655.

Purpose: Anthracycline-based or platinum-based neoadjuvant chemotherapy belongs to the standard treatment for early-stage breast cancer (EBC) that is either triple-negative or human epidermal growth factor receptor 2 positive (HER2 +). Currently, there is a paucity of data comparing their impact on health-related quality of life (HRQoL). Methods: Triple-negative or HER2 + EBC from our two prospective randomized controlled trials, neoCARH and neoCART, were divided into two groups based on the neoadjuvant chemotherapy regimens they received: anthracycline-based or platinum-based group. HRQoL was the exploratory endpoint in these two trials, which was assessed using the European Organization for Research and Treatment of Cancer Quality of Life-Core30 and Breast23 questionnaires. The primary variable of interest was the C30 summary score (C30-SumSc). Assessments were carried out at baseline, after neoadjuvant chemotherapy, and 1 year and 2 years after diagnosis. Results: The mean questionnaires’ compliance rate was 95.0%. After neoadjuvant chemotherapy, 210 patients had evaluable HRQoL data, the mean least square change from baseline for the platinum-based group was − 15.997 (95% confidence interval (CI): − 17.877 to − 14.117), and it was − 20.156 (95% CI: − 22.053 to − 18.258) for the anthracycline-based group (difference: 4.159, 95% CI: 1.462 to 6.855, P = 0.003, minimal important difference = 3). For the majority of the domains of interest assessed by the C30 and BR23 questionnaires, the platinum-based group demonstrated superior outcomes in comparison to the anthracycline-based group. Conclusion: Patients receiving platinum-based or anthracycline-based regimens both experienced worsened HRQoL after neoadjuvant chemotherapy; however, the former provided relatively better HRQoL compared with the latter. Clinical trial registration: ClinicalTrials.gov: NCT03140553. Registered 4 May 2017 (neoCARH). NCT03154749. Registered 16 May 2017 (neoCART). [ABSTRACT FROM AUTHOR]

This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs). A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison. Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations. Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders. PROSPERO ID: CRD42021259826. [ABSTRACT FROM AUTHOR]

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2−) early-stage breast cancer (esBC) is still to be confirmed. Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2− esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early‐stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. Methods: Between 2013 and 2016, 7062 early‐stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early‐stage BC patients who had undergone SLNB. Results: No significant association was observed between obesity and positive SLN rate in early‐stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27–3.95, p = 0.005) and disease‐free survival (HR 1.750, 95% CI 1.16–2.62, p = 0.007) were poorer in patients with high BMI. Conclusion: Obesity is an independent prognostic factor for early‐stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the most common malignancy accounting for 11.7% of all cancer cases, with a rising incidence rate. Various diagnostic methods, including 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), play a crucial role in breast cancer diagnosis and staging. However, the unnecessary use of advanced imaging techniques such as PET/CT in early-stage breast cancer can have negative effects on both economics and patients. We aimed to investigate the impact of PET/CT on the management decisions of early-stage breast cancer patients by the breast cancer tumor board. Methods: A retrospective analysis was performed on a cohort of 81 patients with early-stage breast cancer who were evaluated by breast cancer tumor board from January 2015 to December 2020. Demographic, clinical, and radiographic data, along with surgical procedures and treatment options, were documented and analyzed. Results: The results showed that 18F-FDG PET/CT had a moderate impact on treatment decisions of breast cancer tumor board, as only treatment decisions were changed in 14,86% of the patients. The surgical procedure decision of breast cancer tumor board changed in 12.35% of patients, while 87.65% of patients had consistent decisions before and after PET/CT. Pathological assessments revealed invasive ductal carcinoma as the most prevalent tumor type, and molecular subtypes were predominantly luminal B. PET/CT use had limited impact on surgical procedures and did not significantly alter treatment decisions of breast cancer tumor board in this early-stage breast cancer cohort. Conclusions: In conclusion, this study highlights the importance of adherence to the guidelines and appropriate use of PET/CT in early-stage breast cancer management. PET/CT should be reserved for cases where it is clinically warranted, considering the potential economic burden and minimal impact on treatment decisions of breast cancer tumor board in this patient population. [ABSTRACT FROM AUTHOR]

The object of the study was to conduct a systematic literature review on combined modality treatment for early-stage breast cancer using postoperative and intraoperative radiation therapy, and consider new treatment approaches for early breast cancer.Material and Methods. The search for sources relevant to the review topic was carried out in the Medline, Cochrane Library, and Elibrary systems. A total of 905 studies on combination treatments for early breast cancer were identified, of which 43 were included in the review.Results. Data analysis showed that the rate of local relapses in early breast cancer was lower in patients who underwent breast-conserving surgery in combination with adjuvant radiation therapy than in patients without adjuvant radiation therapy. Research is ongoing on radiotherapy deintensification using intraoperative radiation therapy for patients at low risk of recurrence. Ongoing clinical trials support the omission of radiotherapy after breast-conserving surgery for elderly women with hormone receptor-positive early-stage breast cancer, who receive adjuvant endocrine therapy. Understanding the characteristics of the tumor process will allow us to personalize the treatment of patients with early breast cancer, reduce the risk of local relapses, and avoid unnecessary treatment-related complications.Conclusion. To improve survival in breast cancer patients is only possible by maximizing the tumor control. The effectiveness of adjuvant radiation therapy, which is an integral component in the combined modality treatment of early breast cancer, has been proven. However, third-generation studies discuss the feasibility of identifying a low-risk group of patients with a favorable clinical prognosis, who receive adequate endocrine therapy, and additional radiation do not provide a significant survival benefit.

Thanks to the introduction of new screening programs, the emergence rate of novel anticancer drugs and the detection rate of early-stage breast cancer in Russia increase year by year. Organ preservation treatment, after which radiation therapy has to be performed, is the most common type of surgical treatment used in this cohort of patients. Today, various treatment methods are used, the most common is external beam radiation therapy, however, brachytherapy of breast cancer is also used.

Simple Summary: Breast cancer is the main cause of cancer-related deaths among women globally. It clearly shows it is essential to find a useful marker, which could have a beneficial influence on the prediction of cancer-related events and give more information about the possible outcomes in the early stage of the disease. This is the first study that presents advanced oxidation protein products as a potentially valuable biomarker for monitoring the course of breast cancer treatment and as a predictor of recurrence and cancer-related mortality. The study shows also the relationship between oxidative protein damage in breast cancer patients and excessive angiogenic processes. Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan–Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies comparing performances of machine learning (ML) methods in building predictive models of toxicity in RT are rare. Thanks to the availability of a large cohort (n = 1314) of breast cancer patients homogeneously treated with tangential fields, different ML approaches could be compared. This work shows how more complex models typically achieve higher performances. At the same time, for this test case, the importance is given mainly by a few variables, and toxicity can be predicted by simpler models with similar performances. The availability of more individually characterizing features (here partially missing) is expected to have a likely much higher impact than the choice of the best-performing ML/DL approach. Purpose. Different ML models were compared to predict toxicity in RT on a large cohort (n = 1314). Methods. The endpoint was RTOG G2/G3 acute toxicity, resulting in 204/1314 patients with the event. The dataset, including 25 clinical, anatomical, and dosimetric features, was split into 984 for training and 330 for internal tests. The dataset was standardized; features with a high p-value at univariate LR and with Spearman ρ > 0.8 were excluded; synthesized data of the minority were generated to compensate for class imbalance. Twelve ML methods were considered. Model optimization and sequential backward selection were run to choose the best models with a parsimonious feature number. Finally, feature importance was derived for every model. Results. The model's performance was compared on a training–test dataset over different metrics: the best performance model was LightGBM. Logistic regression with three variables (LR3) selected via bootstrapping showed performances similar to the best-performing models. The AUC of test data is slightly above 0.65 for the best models (highest value: 0.662 with LightGBM). Conclusions. No model performed the best for all metrics: more complex ML models had better performances; however, models with just three features showed performances comparable to the best models using many (n = 13–19) features. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the outcomes of primary endocrine therapy (PET) compared to surgery for treating older women (≥70 years) with early-stage oestrogen-receptor-positive breast cancer, specifically considering the impact of patients' frailty and comorbidity levels. Using UK data from 2000 to 2016, the researchers analysed the all-cause mortality and breast cancer-specific mortality among 23,109 patients, stratified by their Charlson comorbidity index and hospital frailty risk score. The findings showed that surgery generally resulted in better overall survival rates compared to PET in patients with higher levels of frailty or comorbidity. Notably, in very frail older women, there was no significant difference in breast cancer-specific mortality between PET and surgery arms. The study concludes that PET could be a viable treatment option for frail older women with early-stage breast cancer, considering the minimal survival benefits offered by surgery in this subgroup. Primary endocrine therapy (PET) offers non-surgical treatment for older women with early-stage breast cancer who are unsuitable for surgery due to frailty or comorbidity. This research assessed all-cause and breast cancer-specific mortality of PET vs. surgery in older women (≥70 years) with oestrogen-receptor-positive early-stage breast cancer by frailty and comorbidity levels. This study used UK secondary data to analyse older female patients from 2000 to 2016. Patients were censored until 31 May 2019 and grouped by the Charlson comorbidity index (CCI) and hospital frailty risk score (HFRS). Cox regression models compared all-cause and breast cancer-specific mortality between PET and surgery within each group, adjusting for patient preferences and covariates. Sensitivity analyses accounted for competing risks. There were 23,109 patients included. The hazard ratio (HR) comparing PET to surgery for overall survival decreased significantly from 2.1 (95%CI: 2.0, 2.2) to 1.2 (95%CI: 1.1, 1.5) with increasing HFRS and from 2.1 (95%CI: 2.0, 2.2) to 1.4 (95%CI 1.2, 1.7) with rising CCI. However, there was no difference in BCSM for frail older women (HR: 1.2; 0.9, 1.9). There were no differences in competing risk profiles between other causes of death and breast cancer-specific mortality with PET versus surgery, with a subdistribution hazard ratio of 1.1 (0.9, 1.4) for high-level HFRS (p = 0.261) and CCI (p = 0.093). Given limited survival gains from surgery for older patients, PET shows potential as an effective option for frail older women with early-stage breast cancer. Despite surgery outperforming PET, surgery loses its edge as frailty increases, with negligible differences in the very frail. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) is diagnosed as the most common cancer in women in 2022 according to the American Cancer Society. It is essential to detect early and treat early. Several studies have shown that some blood parameters have important predictive value for BC. In this study, we aim to explore whether some immune‐associated blood parameters are relevant to disease‐free survival (DFS) in early‐stage BC. Methods: A single‐center, regression cohort study of 1490 patients with early‐stage BC in Shanghai Cancer Center was conducted from January 2008 to December 2016. The patients were matched according to the ratio of 1:1 based on Propensity Score Matching (PSM). All patients who experienced disease progression were matched successfully. Thus, 58 pairs of subjects were obtained. Matched blood parameters were evaluated by paired samples t‐test or Wilcoxon signed‐rank test. Factors with statistical difference were further evaluated by stratified COX regression model. Results: Univariate analysis showed differences in platelet‐related parameters (PLT, PCT, and PLR) and NLR between the two matched groups. However, stratified COX regression analysis, which ruled out the confounding effects of multiple factors, found that only PCT had prognostic value in early BC patients at baseline and study endpoint. Meanwhile, platelet‐related parameters (PLT, MPV) and NLR were different in the progressive group by self before and after comparison. However, the multiple‐factor analysis showed that only the NLR had prognostic value. ROC curve analysis indicated that the best sensitivity (65.45%) and specificity (78.18%) were obtained when the baseline PCT was 0.225. The optimal sensitivity (70.91%) and specificity (65.45%) were obtained when the PCT of disease progression was 0.215. The Kaplan–Meier curve was used to calculate the DFS rate based on the critical values of the two groups. Conclusions: Some blood parameters have value to predict DFS in early‐stage BC patients, especially platelet‐associated parameters. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1–2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. Results: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014–15 (n = 3,465 of 17,777), 27.1% in 2016–17 (n = 5,140 of 18,985), and 33.6% in 2018–19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). Conclusion: From 2014 to 2019, NAC utilization increased for patients with cT1–2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care. [ABSTRACT FROM AUTHOR]

To determine cardiac dose received by patients treated with high dose rate interstitial brachytherapy. Patients with early-stage, node negative breast cancer can be treated using multi-catheter interstitial brachytherapy accelerated partial breast irradiation (MIB-APBI), with the benefit of reduced treatment volumes and favorable toxicity. We conducted a retrospective review of left-sided breast cancer patients treated using MIB-APBI at our institution since 2014. The mean heart dose (MHD) was calculated using the Oncentra 3.2 planning system. The minimum distance between the planning target volume (PTVeval) and heart contour was measured manually. 81 patients were included. The upper outer quadrant was the most common site. The MHD was 97.8 cGy (EQD2a/b=2) (range 22–229 cGy). MHD significantly correlated with the closest distance between PTVeval and heart contour (correlation coefficient -0.823, p <0.001); size of PTVeval (cc) and quadrant location did not. Appropriately selected women with early-stage, low-risk, left-sided breast cancer who received MIB-APBI had acceptable MHD. There was a strong correlation between the distance of PTVeval and MHD. Quadrant breast tumor is in cannot be used as a surrogate for MHD in brachytherapy. Our findings contribute to the growing evidence of the utility and safety of MIB-APBI. [ABSTRACT FROM AUTHOR]

Axillary lymph node dissection was recommended for mastectomy patients with more than two nodal metastases from sentinel lymph node biopsy. Conventionally, intraoperative frozen section was sent routinely to reduce the need for second-stage axillary lymph node dissection; however, recent global trend has seen decreasing usage of the intraoperative analyses. This pilot study conducted in Thailand aimed to evaluate the role of intraoperative frozen section of sentinel lymph node biopsy in early-stage breast cancer patients who underwent mastectomy. A 5-y retrospective study of 1773 patients was conducted in Thailand. The inclusion criteria were early-stage breast cancer patients with either radiologically negative nodes, or radiographically borderline nodes found to be negative on fine needle aspiration who underwent mastectomy and sentinel lymph node biopsy. Reoperations were indicated when three or more nodal metastases were detected on the pathological analysis. The reoperation rate prevented by frozen section and the reoperation rate needed for those with permanent section alone were reported. Among 265 patients, 202 patients underwent concomitant intraoperative frozen section while the remaining 63 patients underwent permanent section alone. Six patients (3.0%) from the frozen section group and one patient (1.6%) from the permanent section group were found with more than two nodal metastases. Despite using intraoperative frozen sections, only one patient from each group required reoperation. There was no significant difference in the number of patients requiring reoperation between the frozen section group and the permanent section group. Our study provides strong evidence to all surgeons that in early breast cancer patients undergoing mastectomy, sentinel lymph node biopsy with permanent section analysis alone may not lower the standard of care compared to using additional intraoperative frozen section analysis. Adopting this practice may lead to decreased operation costs, operative time, and anesthetic side effects. [ABSTRACT FROM AUTHOR]

Introduction: Multiple studies have demonstrated that the yield of imaging for distant metastatic disease is low in patients with early-stage breast cancer without signs and symptoms of metastatic disease. So, a study was carried out to assess the clinical significance and usefulness of staging investigations in newly diagnosed early-stage breast cancer patients. Materials and method: A retrospective review of medical records of 171 patients with early-stage (stage I & II) breast cancer referred to the Tumor Board & Radiation Oncology department of NICRH and one private hospital after having surgery & adjuvant chemotherapy during the two-year period (January 2019-December 2020), were performed. The staging investigations the patients underwent perioperatively and the value of those in detecting metastasis were evaluated. Result: All patients had chest radiography and routine blood tests performed preoperatively. Postoperative chest radiography evaluation in various frequencies were done in 156 (91.22%) patients. CT scans of the chest were performed in 13 patients (7.6%). One patient (0.64%), who had complained of cough was diagnosed with pulmonary metastasis after evaluation. An ultrasonogram (USG) of the whole abdomen was done preoperatively in 135 patients (78.9%) & postoperatively and subsequently in 162 patients (94.7%) in various frequencies and CT scans of the abdomen were done in 7 patients (4.1%). No metastasis was detected by USG or CT scan of the abdomen. Bone scan was done in 53 patients (31%). Four patients (4/53) were diagnosed with bony metastases out of which 2 had symptoms of bone pain. Routine bone scan can picked up 2(3.7%) bone metastases in asymptomatic patients. Conclusion: Staging investigations for distant metastases in newly diagnosed early-stage breast cancer patients in the absence of signs and symptoms of metastatic disease have low yield, not evidence-based, not cost-effective and thus not recommended. [ABSTRACT FROM AUTHOR]

Abstract Background Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early‐stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. Methods Between 2013 and 2016, 7062 early‐stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early‐stage BC patients who had undergone SLNB. Results No significant association was observed between obesity and positive SLN rate in early‐stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27–3.95, p = 0.005) and disease‐free survival (HR 1.750, 95% CI 1.16–2.62, p = 0.007) were poorer in patients with high BMI. Conclusion Obesity is an independent prognostic factor for early‐stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate.

BackgroundThe NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in node-negative early-stage breast cancer. A sub-study within B-36, focusing on symptoms, quality of life (QOL), menstrual history (MH), and cardiac function (CF) was conducted.Patients and methodsPatients completed the QOL questionnaire at baseline, during treatment, and every 6 months through 36 months. FACT-B Trial Outcome Index (TOI), symptom severity, and SF-36 Vitality and Physical Functioning (PF) scales scores were compared between the two groups using a mixed model for repeated measures analysis. MH was collected at baseline and subsequently assessed if menstrual bleeding occurred within 12 months prior to randomization. Post-chemotherapy amenorrhea outcome was examined at 18 months and was defined as lack of menses in the preceding year. Logistic regression was used to test for association of amenorrhea and treatment. CF assessment was done at baseline and 12 months. Correlation analysis was used to address associations between changes in baseline and 12-month PF and concurrent CF changes measured by LVEF.ResultsFEC-100 patients had statistically significantly lower TOI scores during chemotherapy (P = 0.02) and at 6 months (P

Background: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. Methods: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. Secondary outcomes: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. Results: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were −4 (−10, −1) vs. −6.5 (−15, −2) for TC-H and P-H arms, respectively. Conclusions: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.

With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2−) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined.

Background: A high body mass index (BMI) can indicate overweight or obesity and is a crucial risk factor for breast cancer survivors. However, the association between high BMI and prognosis in early-stage breast cancer (EBC) remains unclear. We aimed to assess the effects of high BMI on the prognosis of patients with EBC. Methods: The PubMed, Embase, and Cochrane Library databases and proceedings of major oncological conferences related to the effects of BMI on the prognosis of breast cancer were searched up to November 2021. Fixed- and random-effects models were used for meta-analyses. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were extracted from the included literature. Results: Twenty retrospective cohort studies with 33,836 patients with EBC were included. Overweight patients had worse DFS (HR: 1.16, 95% CI: 1.05–1.27, P = 0.002) and OS (HR: 1.20; 95% CI: 1.09–1.33, P

The CDK4/6 inhibitor, abemaciclib, is now the standard of care adjuvant therapy for patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) tumors at high risk of recurrence. Real-world usage uncovers emerging side effects that may have been previously unreported in clinical trials. Here, we present the clinical course of a patient who developed a syndrome of inappropriate antidiuretic hormone (SIADH) without underlying kidney injury due to abemaciclib use.

Introduction: Although breast-conserving therapy (BCT) promises at least a similar survival rate for patients with early breast cancer compared with mastectomy, its efficacy in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors remains unclear. Therefore, we conducted this study to explore differential effects of BCT and mastectomy on survival outcomes of patients with early-stage HER2-positive breast cancer. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and basic characteristics of patients who received either BCT or mastectomy were balanced using propensity score matching (PSM). Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards regression were performed. Results: In total, 20,277 patients were diagnosed with T1-2N0-1M0 HER2-positive breast cancer between 2010 and 2015. After PSM, 6,185 pairs of patients were enrolled for further analysis. Compared with those undergoing mastectomy, patients receiving BCT had superior overall survival (OS) (hazard ratio [HR], 0.63; 95% confidence interval [CI]: 0.55–0.73; p < 0.001) and breast cancer-specific survival (BCSS) (HR: 0.59; 95% CI: 0.48–0.71; p < 0.001). The subgroup analyses revealed that survival outcomes (OS and BCSS) of BCT were better than those of mastectomy among estrogen receptor (ER)+/progesterone receptor (PR)+/HER2+, ER+/PR−/HER2+, and ER−/PR−/HER2+ subtypes (p < 0.05 for all); however, patients with ER−/PR+/HER2+ subtypes who underwent BCT had similar OS and BCSS (p > 0.05 for both) to those treated with mastectomy. Discussion/Conclusion: Despite the aggressiveness of the disease, we found that BCT may confer better long-term survival than mastectomy for patients with T1-2N0-1M0 HER2-positive breast cancer, particularly for those with ER+/PR+/HER2+, ER+/PR−/HER2+, and ER−/PR−/HER2+ subtypes. In addition, our study provided insights into the clinical applications of BCT. However, this retrospective study has introduced several inevitable limitations, and further prospective research is warranted to verify these conclusions. [ABSTRACT FROM AUTHOR]

Background/purpose: The psychoneurological (PN) symptom cluster has been defined in the literature as anxiety, depression, fatigue, sleep disturbance, and pain. PN symptoms are influenced by cancer and its treatment as well as biological and psychosocial factors. The purpose of this analysis was to describe temporal patterns of the PN symptom cluster severity in breast cancer survivors over the year following initial surgical intervention and investigate the time-dependent effect of treatment modality on symptom severity. Methods: In a prospective longitudinal study, symptom data were collected from individuals with early-stage breast cancer 48 h after initial surgery and at monthly intervals for the subsequent 12 months using the PROMIS®-29 subscales for anxiety, depression, fatigue, sleep disturbance, and pain. Applying group-based trajectory modeling, we classified participants into subgroups with similar temporal patterns of PN symptom cluster severity and included treatment modality as a time-dependent covariate. Results: Across 353 participants (mean age 60.10 ± 11.9 years, 88.95% white, 66.57% undergoing segmental mastectomies), four distinct trajectory subgroups (mild [47.6%; n = 168], moderate [28.3%; n = 100], severe [15.9%; n = 56], and most severe increasing [8.2%; n = 29]) were revealed for PN symptom cluster severity. Chemotherapy was associated with greater severity in all symptom severity subgroups, while radiation was associated with greater symptom severity in the mild and most severe increasing subgroups. Conclusions and implications: A subgroup of individuals with early-stage breast cancer experienced persistent severe PN symptoms. Future research should focus on psychosocial, biological, and disease-related characteristics of individuals in the most severe symptom group to inform preventative treatments and effective interventions. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have been particularly effective in treating cancers with robust immune microenvironments and have been successfully incorporated into the management of metastatic ER-negative and HER2-negative breast cancer. This has prompted investigation of immunotherapy in early-stage triple negative breast cancer (TNBC) to address the suboptimal clinical outcomes and limited therapeutic options. This review highlights the studies examining the use of neoadjuvant immunotherapy with standard chemotherapy in the management of early-stage TNBC and explores ongoing areas of study including the role of adjuvant checkpoint inhibition and novel combination therapies with immunotherapy. The current standard of care for early-stage ER-negative, HER2-negative breast cancer measuring ≥2 cm or with lymph node involvement is neoadjuvant chemotherapy with pembrolizumab followed by ongoing pembrolizumab in the adjuvant setting to complete 1 year of total therapy as per the KEYNOTE-522 study. This approach is associated with improved pathologic complete response (pCR) rate and event free survival, irrespective of PD-L1 status. Many questions remain regarding the optimization of chemotherapy partner(s) for immunotherapy, necessity of adjuvant immunotherapy for patients who achieve pCR, inclusion of other therapies in the adjuvant setting (particularly capecitabine or olaparib), and use of adjuvant immunotherapy when it was not received in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]

For decades, chemotherapy has been the mainstay of breast cancer treatment. Novel therapies are expanding the therapeutic options and altering the treatment algorithms to manage this disease. The use and approval of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) represent a few areas of progress. These therapies initially gained attention in the metastatic setting but have subsequently found a role in early-stage breast cancer. Although human epidermal growth factor receptor 2 (HER2) is at the center of ADC development, other surface antigens with a differential expression between tumor and normal cells may be appropriate for ADC targeting. This has led to the discovery of new ADCs targeting other receptors, including TROP-2, HER-3, and LIV-1, to name a few. Similarly, the addition of pembrolizumab in treating early-stage triple-negative breast cancer has led to exploring other ICIs in this setting. However, it has also raised important scientific questions regarding optimal patient selection, biomarkers that predict the success of ICIs, ideal chemotherapy partners, and the financial implications of bringing newer therapies to the forefront. In this review, we discuss the evolving landscape of ICIs and ADCs in managing early-stage breast cancer and provide an overview of potential future advancement in the field. [ABSTRACT FROM AUTHOR]

In the past two decades, the survival of HER2-positive early-stage breast cancer patients has significantly improved with the development of HER2-targeted therapies. The focus has been placed on maximizing the clinical benefit of HER2-positive early-stage breast cancer by optimizing the treatment frameworks and therapeutic strategies in this field. In this paper, several important clinical studies of HER2-positive early-stage breast cancer in the neoadjuvant or adjuvant settings will be summarized and analyzed to provide clues for the development of personalized treatment strategies in the future.

Simple Summary: The VGH-TAYLOR study comprised a subgroup of early-stage breast cancer patients. Targeted sequencing was performed for both fresh-frozen paraffin-embedded (FFPE) tumor tissue and plasma. Common genes interrogated by both platforms were identified, and the concordance between paired targeted sequencing results from the same individual is reported. Only one-quarter of breast cancers were concordant between tumor and liquid biopsy from the same subject. Early-stage breast cancer might shed less circulating tumor DNA (ctDNA) from the tumor and compromise the detectability of liquid biopsy. In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ2 test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter. [ABSTRACT FROM AUTHOR]

With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2−) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined. [ABSTRACT FROM AUTHOR]

Background: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. Methods: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. Secondary outcomes: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. Results: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were −4 (−10, −1) vs. −6.5 (−15, −2) for TC-H and P-H arms, respectively. Conclusions: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1 year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factor receptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug. However, neratinib-related toxicity is predictable, short-lived, mostly limited to the first month of treatment and can be managed with dose-escalation and prophylactic strategies. Thus, close surveillance and prompt management, relying on supportive care and administration schedule modification, allows discontinuation of treatment to be avoided. Neratinib, administered within 1 year of trastuzumab, significantly improves disease-free survival in early-stage HER2+ breast cancer, with no increased risk of long-term toxicity. #neratinib #HER2+BC [ABSTRACT FROM AUTHOR]

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as =45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged =45 years. When stratifying by ODx-RS as 0-17 and =18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS =18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS =18 impacting DFS in patients aged =45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (=45 years) with Oncotype Dx recurrence scores of =18 improves DFS. [ABSTRACT FROM AUTHOR]

The current recommendations for surgery for men with breast cancer (MBC) are heavily influenced by clinical studies with only women as participants. Because there have been no clinical trials for the surgical treatment of MBC, we did a systematic review to compare disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) between MBC patients who had breast-conserving surgery (BCS) and those who had a mastectomy. We also looked at radiotherapy compliance among male BCS patients. Objective: The goal of this prospective cohort study is to compare the effectiveness, safety, cost-effectiveness, and cosmetic results of breast conservation surgery (BCS) and mastectomy in treating early-stage breast cancer in developing countries. Material and Method In this prospective cohort study conducted in department of surgery hmc Peshawar from july 2021 t0 july 2022, 100 women with early-stage breast cancer will be randomly given either breast-conserving surgery (BCS) or a mastectomy. The study will be conducted at a single medical center in a developing country. The primary outcome measures will be recurrence-free survival, overall survival, and quality of life. The costs of the two treatments, the cosmetic results, and any side effects will be used as secondary outcome measures. The patients will be followed up for a minimum of 5 years. Results The results of this study will be used to compare the efficacy, safety, cost-effectiveness, and cosmetic outcomes of BCS and mastectomy in the treatment of early-stage breast cancer in developing countries. The primary outcome measure will be recurrencefree survival, overall survival, and quality of life. The costs of the two treatments, the cosmetic results, and any side effects will be used as secondary outcome measures. The patients will be followed up for a minimum of 5 years. Conclusion The results of this study will tell us important things about how well BCS and mastectomy work to treat early-stage breast cancer in developing countries, as well as how safe they are and how much they cost. This information will help doctors in developing countries figure out the best way to treat people with early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Breast‐conserving surgery plus radiation (BCT) yields equivalent or better survival than mastectomy for early‐stage breast cancer (ESBC) women. However, nationwide mastectomy trends increased in recent decades, attracting studies on underlying causes. Prior research identified that long distance to the radiation treatment facility (RTF) was associated with mastectomy. Still, it is unclear whether such association applies to young and old ESBC women comparably. We sought to delineate such impacts by age. Methods Women diagnosed with stages 0–II breast cancer in 2013–2017 receiving either BCT or mastectomy were identified from the Louisiana Tumor Registry. We assessed the association of surgery (mastectomy vs. BCT) with the distance to the nearest or nearest accessible RTFs using multivariable logistic regression adjusting the socio‐demographic and tumor characteristics. The nearest accessible RTF was determined based on patients' health insurance. For Medicaid, uninsured, and unknown insurance patients, the nearest accessible RTF is the nearest RTF owned by the government. The interaction effect of age and distance was evaluated as well. Results Of 11,604 patients, 46.7% received mastectomy. Compared with distance ≤5 miles to the nearest RTF, those with distance ≥40 miles or 15–40 miles had higher odds of mastectomy (adjusted (adj) OR = 1.39, 95% CI = 1.07–1.82; adj OR = 1.17, 95% CI = 1.02–1.34). To the nearest accessible RTF, the adj ORs were 1.25 (95% CI = 1.03–1.51) and 1.19 (95% CI = 1.04–1.35), respectively. Age‐stratified analysis showed the significant association (p

Abstract Breast cancer is the most prevalent disease for women. With advances in breast cancer screening, most breast cancers are now diagnosed in the early stages. With knowledge of different subtypes and their behavior, breast cancer treatment has become more individualized. Radiation therapy as one of the mainstays of breast cancer treatment has also been evolving. This review attempts to provide a summary of the most influential clinical studies that have driven the technological advances in radiation therapy for early‐stage breast cancer.

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens’ decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions.

Background: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. Methods: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0–6 weeks prior to and 0–6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16–19.09) years. Results: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). Conclusions: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. Clinical Trial registration: The trial is registered (2 May 2019) at trials.gov under NCT03935802.

Abstract Introduction An increasing number of postmenopausal women are diagnosed with breast cancer at an older age (≥ 70 years). There is a lack of synthesised health utility data to support decision-making for managing breast cancer in this older population. This study aimed to identify the availability of, and the subsequent impact of age on, health state utility values (HSUVs) measured by the EQ-5D for older women with early-stage breast cancer. Method This systematic review identified EQ-5D (3L or 5L version) HSUVs for postmenopausal women with early-stage breast cancer. Studies were identified from a previous systematic review (inception to 2009) and an electronic database search (Medline and Embase; 2009 to September 2021). Mean HSUVs were summarised by health state. Quality appraisal was performed on studies reporting HSUVs for older ages (≥ 70 years). Multivariable meta-regression assessed the association between HSUVs and age, health state, treatments received, and time of measuring the utility values (greater or less than one year post-treatment). Results Fifty EQ-5D HSUVs were identified from 13 studies. Mean HSUVs decreased as health state worsened: from the stable (mean=0.83) to progression (mean=0.79) and advanced (mean=0.68) states. Two studies reported six HSUVs estimated from the sample of women with a mean age ≥ 70. Meta-regression model fit improved by including age as an independent variable and attenuated the estimated utility decrements associated with worse health states. Utility decrements for the progression and advanced states were -0.052 (95%CI: -0.097, -0.007) and -0.143 (95%CI: -0.264, -0.022) respectively. The breast cancer-specific utility decrement associated with a one-year increase in age was -0.001 (95%CI: -0.004, 0.002). Conclusion Relevant and accurate HSUVs are essential to help support decision-making about the most effective and cost-effective ways to manage early-stage breast cancer in older women. Age has a vital role in determining health utility values in this population. This study provides analysts and decision-makers with HSUVs and utility decrements that reflect the disease process in this older population.