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Introduction: One of the most feared side effects of radiotherapy (RT) in the setting of breast cancer (BC) patients is cardiac toxicity. This side effect can jeopardize the quality of life (QoL) of long-term survivors. The impact of modern techniques of RT such as deep inspiration breath hold (DIBH) have dramatically changed this setting. We report and discuss the results of the literature overview of this paper. Materials and methods: Literature references were obtained with a PubMed query, hand searching, and clinicaltrials.gov. Results: We reported and discussed the toxicity of RT and the improvements due to the modern techniques in the setting of BC patients. Conclusions: BC patients often have a long life expectancy, thus the RT should aim at limiting toxicities and at the same time maintaining the same high cure rates. Further studies are needed to evaluate the risk–benefit ratio to identify patients at higher risk and to tailor the treatment choices. [ABSTRACT FROM AUTHOR]

Purpose: Tumor-associated macrophages (TAM) may participate to antitumor activity of anti-HER2-targeted therapies (Pertuzumab, Trastuzumab) in breast cancers harbouring HER-2 overexpression through antibody-dependent phagocytosis. Additive antitumor effect of concurrent cytotoxic chemotherapies, including Paclitaxel, may be counterbalanced by alteration in TAM infiltrate. The aim of this study is to evaluate the role of TAM in tumor response to anti-HER2-targeted therapies and chemotherapy in an experimental model of HER2-amplified breast cancer. Methods: A xenograft mouse model was built by subcutaneous injection of the SKBR-3 human HER2-amplified breast cancer cell line in Hu-CD34+ mice. Animals were randomized to receive weekly administration of Cremophor (control), Trastuzumab+Pertuzumab (TP), and Paclitaxel+Trastuzumab+Pertuzumab (PTP) with or without macrophage depletion with clodronate (C). At week 4, mice were euthanised and tumors were harvested for immunohistochemical analysis of TAM infiltration (RBP-J CD163 and CD68 for M1, M2, and overall TAM, respectively). Results: Tumor size was significantly lower in mice treated with TP, PTP, and PTP+C as compared to control, while no meaningful difference was observed in the TP+C arm. Analysis of TAM infiltrate showed significantly lower CD68 and CD163 expression in PTP, TP+C, and PTP+C as compared to TP and control arm. RBP-J expression was significantly decreased in mice treated with clodronate depletion. Conclusions: Activity of TP is modulated by TAM infiltrate, that is inhibited by concurrent administration of Paclitaxel. To enhance the effect of anti-HER2-targeted therapies and minimize chemotherapy-related side effects, modulation of TAM should be considered in novel therapeutic combinations. [ABSTRACT FROM AUTHOR]

Background: The plasma concentration of endoxifen, the active metabolite of tamoxifen, might be affected by different CYP2D6 genotypes in patients with breast cancer, but solid evidence is still lacking in Asian patients. This prospective study aimed to investigate the relationship between CYP2D6 genetic polymorphisms and endoxifen plasma concentrations among Chinese patients with breast cancer treated with tamoxifen. Methods: From August 2015 to June 2018, 110 patients with breast cancer were enrolled. CYP2D6 variant alleles and endoxifen plasma concentration were determined using Sanger sequencing and high-performance liquid chromatography-tandem mass spectrometry, respectively. Results: The most frequent allele of CYP2D6 was *10 (56.4%). The most frequent genotype of CYP2D6 was *10/*10 (33%), *1/*10(28.2%) and *2/*10(14.5%). Sixty-four patients (58.2%) were Normal Metabolizers (NM), while 46 (41.8%) were Intermediate Metabolizers (IM). All patients except two had endoxifen concentrations above the threshold of 5.9ng/ml. The median endoxifen plasma concentrations for patients with CYP2D6 genotypes *1/*2 and *1/10 were higher compared to other genotypes (p = 0.012). The median endoxifen plasma concentration was higher in NM than in IM (18ng/ml vs. 13ng/ml, p = 0.0077). Patients with CYP2D6*10(T/T) had lower endoxifen concentrations than those with *10(C/T) and *10(C/C) but the difference was not significant. There were no significant differences in adverse events between patients in the NM and IM groups or between patients with the CYP2D6*10 (T/T) genotype and non-*10 (T/T) genotype. Conclusion: Only CYP2D6 IMs and NMs were identified in this study. Almost all patients had the endoxifen concentrations above the threshold. The endoxifen plasma concentration was lower in CYP2D6 IMs than in NMs, but these variants did not compromise the adverse effects of tamoxifen in Asian patients with breast cancer. Trial registration: The study protocol was approved by the institutional review boards of Sun YatSen University Cancer Center (Ethics approval number, B201506501,20160115). [ABSTRACT FROM AUTHOR]

Purpose of Review: Triple negative breast cancer remains a diagnosis that strikes fear into patients and providers alike due to its associated treatment challenges and natural history. The recent decades have seen significant advances in the field of breast cancer radiation oncology, and in this review we seek to highlight current standards of care, the historic basis for current recommendations, and future directions. Recent Findings: Advances in the field of breast radiation oncology have been numerous in the recent decades and include various hypofractionated regimens, new data and nuances in the administration of regional nodal radiation, new systemic agents and combinations with radiotherapy, and novel strategies that radically change current treatment paradigms. In this review, we will navigate the applicability of these data and approaches to the management of triple negative breast cancer. Summary: Triple negative breast cancer remains a challenging disease process, but one that we have seen considerable advancement in the management of in the recent decades. We are optimistic that patients will continue to benefit from treatment approaches that improve disease control and quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: The omission of axillary surgery is gaining popularity in selected groups of breast cancer patients. On the other hand, the exceptional nodal responses to neoadjuvant chemotherapy and dual Her2 blockage in Her2-positive breast cancer patients opens the way to the question of whether we can omit axillary surgery in such a group of patients or at least in a certain subgroup. This study aimed to evaluate the lymph node pathological status after neoadjuvant therapy in Her2+ breast cancer patients and to highlight the variables that can predict a pathological complete nodal response so that it can be expected without the need for surgical axillary staging Background: This study aimed to evaluate the lymph node (LN) response in Her2-positive breast cancer patients who received neoadjuvant therapy (NAT) and to discuss if axillary staging can be omitted in these patients. Methods: This is a retrospective cohort study including patients with Her2+ breast cancer at our center from March 2022 to September 2023. Results: The study included 139 patients in the final analysis; 69.1% of the patients had HR+/Her2+ disease while 30.9% had HR−/Her2+ disease. Most of the included patients (129 patients = 92.8%) had initially node-positive or suspicious disease. A total of 112 patients (80.6%) showed clinically negative axillary LNs (cN0) after NAT. All of them showed pathologically node-negative disease. When comparing the pathological node-positive vs. -negative groups, the following was found to be statistically significant: degree of Her2 positivity, number of anti-Her2 cycles, pre- and post-neoadjuvant LN status, and primary tumor radiological and pathological response. Also, all T1 tumors before NAT showed negative LNs after NAT, but it was statistically non-significant. Conclusions: Axillary staging may be omitted in Her2+ patients with cN0 after NAT, especially those with early tumors, strong Her2+ disease, cN0 before NAT, and those in whom the primary tumor achieved a complete clinical response. [ABSTRACT FROM AUTHOR]

Background/Objectives: The most common type of breast cancer (BRC) in women is estrogen/progesterone receptor positive. First-line treatment includes endocrine therapy, either with aromatase inhibitors or tamoxifen to reduce estrogen levels. Among the side effects produced by this treatment, aromatase inhibitor-induced arthralgia is the most common, affecting the patients' overall health and quality of life (QoL). The objectives here were to evaluate interventions examining the impact of modified diets, supplements, and/or some food components on health outcomes in BRC patients undergoing endocrine therapy. Methods: The literature search was performed in PubMed, Scopus, and Web of Science from June 2024, as well as manually, through the end of November 2024. The search was limited to studies of women diagnosed with estrogen/progesterone-receptor-positive BRC with selected articles reporting interventions with diet, food, or supplement intake and examining the relevant health outcomes. Studies not focusing on BRC patients undergoing endocrine therapy or not including specific health outcomes were excluded. Results: The search uncovered 1028 studies; after the removal of duplicates, abstracts, and irrelevant studies, 53 were closely examined, with 26 evaluated and presented here. The outcomes were changes in bone and body composition, cardiovascular disease risks, inflammation, and QoL. Conclusions: The examined evidence suggests that adherence to dietary patterns such as the Mediterranean or a low-fat diet, and a higher intake of fruits and vegetables were beneficial for various outcomes. Additionally, supplementation with some foods/components (dried plum, red clover) contributed to improving/maintaining bone and body composition, especially in overweight/obese patients. Supplementation with vitamin D or omega-3 improved lipid and angiogenic parameters and QoL. Although these results are promising, the effects of each supplement/food cannot be summarized due to the diverse nature of study designs, patients, and supplement dosages. Further studies are needed to explore the effects of specific nutritional interventions (including the newest, like fasting-mimicking diets and whole-grain cereal diets) on various health outcomes in BRC survivors during endocrine therapy, and to derive universal recommendations. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most prevalent cancers worldwide. Recent studies have increasingly emphasized the role of oxidative stress in the initiation and progression of breast cancer. This article reviews how oxidative stress imbalance influences the occurrence and advancement of breast cancer, elucidating the intricate mechanisms through which reactive oxygen species (ROS) operate in this context and their potential therapeutic applications. By highlighting these critical insights, this review aims to enhance our understanding of oxidative stress as a potential target for innovative therapeutic strategies in the management of breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. Methods: This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the riskadapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. Results: The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%- 3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). Conclusions: This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is characterised by the lack or low expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. TNBC has a high recurrence rate, swiftly metastasizes, and has a high mortality rate. Subsequently, the increase in cases of TNBC has signaled the need for treatment strategies with improved drug delivery systems. New diagnostic approaches, chemical entities, formulations particular those in the nanometric range have emerged after extensive scientific research as alternative strategies for TNBC treatment. As compared to contemporary cancer therapy, nanoparticles offer peculiar tunable features namely small size, shape, electrical charge, magnetic and fluorescent properties. Specifically in targeted drug delivery, nanoparticles have been demonstrated to be highly efficient in encapsulating, functionalization, and conjugation. Presently, nanoparticles have ignited and transformed the approach in photodynamic therapy, bioimaging, use of theranostics and precision medicine delivery in breast cancer. Correspondingly, recent years have witnessed a drastic rise in literature pertaining to treatment of TNBC using nanomaterials. Subsequently, this manuscript aims to present a state-of-the-art of nanomaterials advance on TNBC treatment; the ubiquitous utility use of nanomaterials such as liposomes, dendrimers, solid lipid nanomaterials, gold nanomaterials and quantum dots as anticancer agents and drug delivery systems in TNBC. [ABSTRACT FROM AUTHOR]

Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume. [ABSTRACT FROM AUTHOR]

Background: Early-stage breast cancer (BC) presents a certain risk of recurrence, leading to variable prognoses and complicating individualized management. Yet, preoperative noninvasive tools for accurate prediction of disease-free survival (DFS) are lacking. This study assessed the potential of strain elastography (SE) and diffuse optical tomography (DOT) for non-invasive preoperative prediction of recurrence in T1 BC and developed a prediction model for estimating the probability of DFS. Methods: A total of 565 eligible patients with T1 invasive BC were enrolled prospectively and followed to investigate the recurrence. The associations between imaging features and DFS were evaluated and a best-prediction model for DFS was developed and validated. Results: During the median follow-up period of 10.8 years, 77 patients (13.6%) developed recurrences. The fully adjusted Cox proportional hazards model showed a significant trend between an increasing strain ratio (SR) (P < 0.001 for trend) and the total hemoglobin concentration (TTHC) (P = 0.001 for trend) and DFS. In the subgroup analysis, an intensified association between SR and DFS was observed among women who were progesterone receptor (PR)-positive, lower Ki-67 expression, HER2 negative, and without adjuvant chemotherapy and without Herceptin treatment (all P < 0.05 for interaction). Significant interactions between TTHC status and the lymphovascular invasion, estrogen receptor (ER) status, PR status, HER2 status, and Herceptin treatment were found for DFS(P < 0.05).The imaging–clinical combined model (TTHC + SR + clinicopathological variables) proved to be the best prediction model (AUC = 0.829, 95% CI = 0.786–0.872) and was identified as a potential risk stratification tool to discriminate the risk probability of recurrence. Conclusion: The combined imaging-clinical model we developed outperformed traditional clinical prognostic indicators, providing a non-invasive, reliable tool for preoperative DFS risk stratification and personalized therapeutic strategies in T1 BC. These findings underscore the importance of integrating advanced imaging techniques into clinical practice and offer support for future research to validate and expand on these predictive methodologies. [ABSTRACT FROM AUTHOR]

Background. The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. Methods. We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. Results. Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5–82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3–97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7–79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5–87.9%). Importantly, no local progression was observed after RT when using high doses. Conclusions. The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context. [ABSTRACT FROM AUTHOR]

Objective: Reports demonstrating the effectiveness and safety of strut-adjusted volume implants (SAVI) in Japan are limited. Therefore, this study aimed to compare the treatment outcomes of SAVI and whole-breast irradiation (WBI) at a single facility. Materials and Methods: Data were retrospectively extracted from the medical records of patients treated with SAVI or WBI following partial mastectomy (Bp). Patients undergoing Bp, sentinel lymph node biopsy, and SAVI spacer insertion followed by brachytherapy with the SAVI device were compared to those followed with WBI. Local recurrence was assessed annually by physical examination, bilateral mammography, and breast ultrasonography. Results: The SAVI and WBI groups comprised 53 and 113 patients, with a median age of 55 and 52 years, respectively; among them, 47 and 91 patients had a pathological tumor diameter ≤2 cm and six and 22 had a pathological tumor diameter >2 cm, respectively. Recurrence events, acute adverse events, and late adverse events were observed in the SAVI and WBI groups in 1 and 3 (p = 0.726), 24 and 79 (p = 0.01), and 24 and 18 patients (p = 0.00002), respectively, with median observation periods of 60.0 and 47.8 months, respectively. All adverse events were grades 1-2, with dermatitis being the most common in the acute phase. In the late phase, pigmentation was common in both groups. Conclusion: The local recurrence rate does not differ between SAVI and WBI within the relatively short-term follow-up period. Longer follow-up is required to confirm our results in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real‐world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC. Methods: This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti‐HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use. Results: Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients <35 years were more likely to receive OS compared with those ≥35 years (odds ratio 2.33, p < 0.001). Conclusions: This is the first real‐world study evaluating ET treatment patterns in HR+/HER2+ premenopausal BC. OS use was uncommon and the majority received tamoxifen as the preferred ET regardless of most clinicopathologic risk factors. Additional research is needed to optimize ET decisions in young women with this distinct BC subtype. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer characterized by poor prognosis. The treatment requires a multidisciplinary approach, with neoadjuvant chemotherapy, surgery, and radiation therapy (RT). Particularly, high doses of conventional RT have been historically delivered in the adjuvant setting after chemotherapy and mastectomy or as radical treatment in patients ineligible for surgery. Here, we report the case of a 49-year-old woman patient with IBC unsuitable for surgery and treated with a combination of lattice RT and fractionated external beam RT concurrent with trastuzumab, with a curative aim. One year after RT, the patient showed a complete response and tolerable toxicities. This is the first reported case of a not-operable IBC patient treated with this particular kind of RT. [ABSTRACT FROM AUTHOR]

Introduction: Cancer related cognitive decline is a common long-term side effect of cancer and its treatments among breast cancer survivors. Physical activity is a modifiable risk factor related to cognitive decline. However, existing research lacks consensus regarding the relationship between cognition and exercise as well as the impact of cancer treatments on this relationship. Baseline data from an ongoing randomized clinical trial was utilized to examine the relationship between self-reported and objectively measured cognition with physical activity. Exploratory analyses examined cancer treatments as potential moderators. Methods: Breast cancer survivors (N = 253) completed a battery of neurocognitive tests, the PROMIS Cognitive abilities questionnaire, medical charts abstracted for treatment information, and wore an ActiGraph accelerometer at the waist for 7 days. Data were analyzed using multiple linear regression models. Results: Participants were on average 58.5 (SD = 8.88) years old, diagnosed 3 years prior to enrollment (SD = 1.27) with 57% treated with chemotherapy and 80% receiving hormone therapy at baseline. Better self-reported cognitive ability was significantly associated with greater min of moderate to vigorous physical activity (MVPA; b = 0.070, se = 0.028, p = 0.012). There were no significant associations with any objectively measured cognitive domains. Time since diagnosis (years) was a significant moderator of MVPA and Processing Speed (b = -0.103, se = 0.043, p = 0.017). Treatment with chemotherapy and/or hormones did not significantlymoderate the relationship betweenMVPA and any of the cognitive measures or domains. Conclusion: Findings suggest that physical activity is related to self-reported cognition but not objectively measured cognition. Greater physical activity was associated with faster processing speed in participants closer in time to their cancer diagnosis. These results emphasize the need for more research to understand when cancer survivors may benefit from physical activity and what aspects of cognition may be improved. [ABSTRACT FROM AUTHOR]

Background: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. Methods: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 − (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 − and AST 2 + groups and cutoff value calculations. Results: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71–0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. Conclusions: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST. [ABSTRACT FROM AUTHOR]

Background/Aim: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immunohistochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece. Patients and Methods: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm. Results: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triplenegative phenotype (p=0.001). Conclusion: The study provided valuable insights into the histopathological and immunohistochemical characteristics involved in the development and progression of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Adjuvant radiotherapy represents a key component in curative-intent treatment for early-stage breast cancer patients. In recent years, two accelerated partial breast irradiation (APBI) techniques are preferred for this population in our organization: electron-based Intraoperative radiation therapy (IORT) and Linac-based External Beam Radiotherapy, particularly Intensity-modulated radiation therapy (IMRT). Recently published long-term follow-up data evaluating these technologies have motivated a health technology reassessment of IORT compared to IMRT. Methods: We developed a Markov model to simulate health-state transitions from a cohort of women with early-stage breast cancer, after lumpectomy and adjuvant APBI using either IORT or IMRT techniques. The cost-effectiveness from a private health provider perspective was assessed from a disinvestment point of view, using life-years (LYs) and recurrence-free life-years (RFLYs) as measure of benefits, along with their respective quality adjustments. Expected costs and benefits, and the incremental cost-effectiveness ratio (ICER) were reported. Finally, a sensitivity and scenario analyses were performed to evaluate the cost-effectiveness using lower IORT local recurrence and metastasis rates in IORT patients, and if equipment maintenance costs are removed. Results: IORT technology was dominated by IMRT in all cases (i.e., fewer benefits with greater costs). Despite small differences were found regarding benefits, especially for LYs, costs were considerably higher for IORT. For sensitivity analyses with lower recurrence and metastasis rates for IORT, and scenario analyses without equipment maintenance costs, IORT was still dominated by IMRT. Conclusions: For this cohort of patients, IMRT was, at least, non-inferior to IORT in terms of expected benefits, with considerably lower costs. As a result, IORT disinvestment should be considered, favoring the use of IMRT in these patients. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a rare and highly invasive form of breast cancer, renowned for its aggressive behavior, malignant capacity, and unfavorable prognosis. Despite considerable advancements in comprehending the underlying biology of IBC, the immune cell infiltration (ICI) profile in IBC remains inadequately elucidated. The current work endeavors to investigate the ICI characteristics of IBC and ascertain the pivotal immune cell subtypes and genes that impact its prognosis. The present study employed microarray data from the GEO database to demonstrate that IBC exhibited a lower abundance of activated mast cells (AMC) in comparison to non-inflammatory breast cancer (nIBC) or normal breast tissue (NBT). Additionally, the mRNA expression level of the gene polo-like kinase 5 (PLK5), which was correlated with AMC, was found to be lower in IBC relative to nIBC or NBT. Furthermore, this investigation provided compelling evidence indicating a potential association between a decreased mRNA expression level of PLK5 and a shorter progression-free survival in patients with breast cancer. The gene set enrichment analysis performed on PLK5 revealed that the gene expression in IBC was closely associated with diverse immune functions and pathways. Besides, a negative correlation has been established between PLK5 mRNA expression level and a majority of immune checkpoint-related genes, thereby suggesting the potential suitability of immunotherapy treatment for IBC. In summary, this study offers valuable insights into the ICI profile of IBC and identifies potential target PLK5 for improving its clinical management. [ABSTRACT FROM AUTHOR]

Purpose We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1- 2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients. Materials and Methods Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews correlation coefficient (MCC) were determined for each guideline. Results A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea. Conclusion The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Accelerated partial-breast irradiation (APBI) has gained acceptance in the last few years as a postoperative treatment after breast-conserving therapy. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS and APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year ipsilateral breast tumor recurrence (IBTR) was 1.7% (95%CI: 0.7–2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2–96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients. Patients with an early carcinoma of the breast are commonly treated by breast-conserving surgery (BCS) and postoperative radiotherapy. Partial-breast irradiation has gained acceptance in the last few years. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS in the four university hospitals of the province of Las Palmas and treated with APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year IBTR was 1.7% (95%CI: 0.7–2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2–96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to study intratumoral heterogeneity in the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) between two different cores/blocks of core needle biopsy (CNB), two different blocks of the same lesion in resection specimen (RS), and in between the CNB and RS. Materials and Methods: This is a prospective observational study of all the cases of breast carcinoma received in the department of histopathology for 2 years. All the patients with breast carcinoma diagnosed by CNB and RS were analyzed by three pathologists independently by immunohistochemistry. Results: Of the 75 cases, 74 were females and 1 male with a peak incidence of 60–70 years. Invasive breast carcinoma of no special type (97%) was the most common, followed by invasive lobular carcinoma (3%). Grade III tumors (44%) were more common, followed by Grade II (39%) and Grade I (17%). ER and PR showed a concordance rate of 96% (P < 0.05), whereas the HER2 showed a concordance rate of 93% (P < 0.05%). The concordance of ER decreased with increasing tumor size and grade, while PR and HER2 showed variable concordance with tumor size and grade. Conclusion: The concordance rate of ER and PR (96%) was higher than (93%) HER2. In most cases, biomarker expression in core biopsy and single tumor block was reflective of breast carcinoma as a whole. However, because of the heterogeneous expression of biomarkers, we recommend testing tumors with negative biomarker expression on CNB, again on the RS. [ABSTRACT FROM AUTHOR]

Breast cancer is diagnosed in nearly 3 million people worldwide. Radiation therapy is an integral component of disease management for patients with breast cancer, and is used after breast-conserving surgery or a mastectomy to reduce the risk of a local recurrence. The following review describes the methods used to personalize radiation therapy by optimizing patient selection, using advanced treatment techniques to lessen the radiation dose to normal organs, and using hypofractionation in order to shorten the duration of radiation treatment. [ABSTRACT FROM AUTHOR]

The aim of this article is to discuss the challenges and new strategies in managing breast cancer patients, with a specific focus on radiation oncology and the importance of balancing oncologic outcomes with quality of life and post-treatment morbidity. A comprehensive literature review was conducted to identify advances in the management of breast cancer, exploring de-escalation strategies, hypofractionation schemes, predictors and tools for reducing toxicity (radiation-induced lymphocyte apoptosis, deep inspiration breath-hold, adaptive radiotherapy), enhancer treatments (hyperthermia, immunotherapy) and innovative diagnostic modalities (PET-MRI, omics). Balancing oncologic outcomes with quality of life and post-treatment morbidity is crucial in the era of personalized medicine. Radiotherapy plays a critical role in the management of breast cancer patients. Large randomized trials are necessary to generalize some practices and cost remains the main obstacle for many innovations that are already applicable. [ABSTRACT FROM AUTHOR]

Background: Accelerated partial breast irradiation (APBI) is an alternative breast-conserving therapy approach where radiation is delivered in less time compared to whole breast irradiation (WBI), resulting in improved patient convenience, less toxicity, and cost savings. This prospective randomized study compares the external beam APBI with commonly used moderate hypofractionated WBI in terms of feasibility, safety, tolerance, and cosmetic effects. Methods: Early breast cancer patients after partial mastectomy were equally randomized into two arms– external APBI and moderate hypofractionated WBI. External beam technique using available technical innovations commonly used in targeted hypofractionated radiotherapy to minimize irradiated volumes was used (cone beam computed tomography navigation to clips in the tumor bed, deep inspiration breath hold technique, volumetric modulated arc therapy dose application, using flattening filter free beams and the six degrees of freedom robotic treatment couch). Cosmetics results and toxicity were evaluated using questionnaires, CTCAE criteria, and photo documentation. Results: The analysis of 84 patients with a median age of 64 years showed significantly fewer acute adverse events in the APBI arm regarding skin reactions, local and general symptoms during a median follow-up of 37 months (range 21–45 months). A significant difference in favor of the APBI arm in grade ≥ 2 late skin toxicity was observed (p = 0.026). Late toxicity in the breast area (deformation, edema, fibrosis, and pain), affecting the quality of life and cosmetic effect, occurred in 61% and 17% of patients in WBI and APBI arms, respectively. The cosmetic effect was more favorable in the APBI arm, especially 6 to 12 months after the radiotherapy. Conclusion: External APBI demonstrated better feasibility and less toxicity than the standard regimen in the adjuvant setting for treating early breast cancer patients. The presented study confirmed the level of evidence for establishing the external APBI in daily clinical practice. Trial registration: NCT06007118. [ABSTRACT FROM AUTHOR]

Whole breast irradiation after breast‐conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high‐dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 10% of breast cancer (BC) cases are hereditary, and germline pathogenic variants in BRCA1 and BRCA2 genes account for 20% of familial BC cases. Long-term follow-up data related to the prognosis and survival of either BRCA1 or BRCA2 BC patients are conflicting. The aim of this study is to report the analysis of our cohort of BRCA1/2 BC patients included in prospective follow-up after genetic testing. We compared clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 and a control group without germline PV (BRCA-wt). The presence of BRCA mutation confers a higher risk of relapse and death in patients with BC in the Portuguese population. Prophylactic mastectomy and preventive salpingo-oophorectomy confer lower incidence of relapse and longer median invasive disease-free survival and overall survival, respectively. Background: Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BRCA1 BC patients, yielded conflicting results regarding BRCA1/2 BC outcomes. In the Portuguese population, BRCA2 BC is diagnosed more frequently than BRCA1 BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries in BRCA-mutated patients. Methods: Prospective follow-up was proposed for patients with a diagnosed BRCA1/2 PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among the BRCA cohort. Results: For a mean follow-up time of 113.0 months, BRCA-wt patients showed longer time to recurrence (p = 0.002) and longer OS (p < 0.001). Among patients with BRCA mutations, no statistical differences were found, although patients with BRCA2 BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. Conclusions: Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively. [ABSTRACT FROM AUTHOR]

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to explore the role of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elder womenwith early-stage breast cancer (BC). Methods: BC patients with 70-79 years of age, stage T1-2N0-1M0, undergoing BCS were screened in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The clinicopathological characteristics were balanced with propensity-score matching (PSM) method. Kaplan--Meier curves and Cox regression analyses were performed to determine the impact of adjuvant RT on BC patients. Results: Ultimately, 12,310 patients treated with adjuvant RT and 4837 patients treated with no RT, were involved in the analysis. Overall, patients treated with adjuvant RT was associated with a better breast cancer-specific survival (BCSS) (HR: 1.980 [1.596- 2.456], P < 0.001) and overall survival (OS) (HR: 2.214 [1.966- 2.494], P < 0.001) than those who did not undergo RT. After 1:1 PSM, adjuvant RT still performed advantage in both BCSS (HR: 1.918 [1.439- 2.557], P < 0.001) and OS (HR: 2.235 [1.904- 2.624], P < 0.001). In the multivariate COX analysis of BCSS, widowed, divorced and separated patients, tumor grade III, T2 stage, N1 stage, no RT, molecular subtypes with luminal B and triple negative were associated with a shorter BCSS (P < 0.05). In the multivariate COX analysis of OS, age ≥74 years, widowed, divorced and separated patients, tumor grade II/III, T2 stage, no RT, no chemotherapy, molecular subtypes with triple negative were associated with a shorter OS (P < 0.05). Furthermore, the advantages of adjuvant RT were observed in all subgroup analysis. Conclusion: Adjuvant RT after BCS can improve both BCSS and OS in elderly patients with early-stage BC. Additionally, all subgroups analysis-derived BCSS and OS were in support of RT. [ABSTRACT FROM AUTHOR]

Breast cancer (BC), one of the most widespread and devastating diseases affecting women worldwide, presents a significant public health challenge. This review explores the emerging frontiers of research focused on deciphering the intricate interplay between BC cells and the immune microenvironment. Understanding the role of the immune system in BC is critical as it holds promise for novel therapeutic approaches and precision medicine strategies. This review delves into the current literature regarding the immune microenvironment's contribution to BC initiation, progression, and metastasis. It examines the complex mechanisms by which BC cells interact with various immune cell populations, including tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Furthermore, this review highlights the impact of immune-related factors, such as cytokines and immune checkpoint molecules. Additionally, this comprehensive analysis sheds light on the potential biomarkers associated with the immune response in BC, enabling early diagnosis and prognostic assessment. The therapeutic implications of targeting the immune microenvironment are also explored, encompassing immunotherapeutic strategies and combination therapies to enhance treatment efficacy. The significance of this review lies in its potential to pave the way for novel therapeutic interventions, providing clinicians and researchers with essential knowledge to design targeted and personalized treatment regimens for BC patients. [ABSTRACT FROM AUTHOR]

Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p < .001), 90.77% (kappa, 0.812; p < .001), 69.62% (kappa, 0.482; p < .001), and 86.92% (kappa, 0.552; p < .001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess the outcomes and toxicity of patients treated with concurrent administration of CDK4/6 inhibitors (CDK4/6i) and locoregional radiation therapy (RT), including the breast with a boost or the thoracic wall after mastectomy and the regional lymph node areas. We retrospectively analyzed data from 27 patients with hormone receptor‐positive, HER2‐negative de novo metastatic breast cancer treated with CDK4/6i and concomitant locoregional RT in 2017/2022. Survival rates were calculated by Kaplan‐Meier method. Prognostic factors were tested with log‐rank test. CDK4/6i was used as the first systemic metastatic treatment for all the patients, and the median overall treatment time was 26 months. The median time from initiation of CDK4/6i to the start of RT was 10 months (IQR: 7‐14 months). The median duration of concomitant CDK4/6i and RT administration was 21 days (IQR: 14.5‐23 days). After a median follow‐up of 19 months (IQR: 14‐36 months), 1 patient died, 11/27 had distant metastases and 1 patient had local recurrence, respectively. The 1‐ and 3‐years progression‐free survival (PFS) were 61.4% (95% CI: 45.1%‐83.7%) and 53.7% (35.8%‐80.5%), respectively. The acute toxicities most observed during RT were neutropenia (44%) and dermatitis (37%). Dermatitis was significantly more frequent in patients with large target volumes (CTV > 911 cc and PTV > 1285 cc). CDK4/6i had to be discontinued in five patients during RT (due to toxicity in three cases and disease progression in two cases). One patient has developed grade 2 late pulmonary fibrosis. Finally, our study demonstrated that concurrent administration of locoregional RT and CDK4/6i did not induce severe late toxicity for most patients. [ABSTRACT FROM AUTHOR]

Purpose of review: Sequential use of radiation therapy before cyclin-dependent kinase (CDK) inhibitors in women with early breast cancer seems reasonable and with a low toxicity rate. This study aimed to evaluate the possible interaction between RT and CDK inhibitors in the adjuvant setting for patients with positive hormone receptors and HER-2 negative, investigating toxicity and the treatment sequencing. Recent findings: CDK inhibitors have been studied in patients with localized breast cancer and can improve invasive disease-free survival outcomes. Regarding the time of RT, all trials used CDK inhibitors after the RT. Interruptions in the CDK inhibitors were performed in 27.1% in Pallas, 17.5% in Penelope-B, and 16.6% in Monarch-E trials due to adverse events. Data from the Natalee trial are still not reported. The main adverse event grade III was neutropenia, with good resolution of the symptoms over time. Summary: CDK inhibitors applied sequentially and after RT postoperative showed a low profile of acute toxicity and suitable oncological outcomes. [ABSTRACT FROM AUTHOR]

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in the contralateral breast for long-term survivors of breast cancer. Individually estimated radiation absorbed doses to the four quadrants and areola central area of the contralateral breast were estimated for 2,132 women treated with radiation therapy for local/regional breast cancers at age <55 years diagnosed between 1985 and 2008. The two inner quadrant doses and two outer quadrant doses were averaged. Trends in dose to each of the three areas of the contralateral breast were evaluated in multivariable models. The population impact of reducing contralateral breast dose on the incidence of radiation-associated CBC was assessed by estimating population attributable risk fraction (PAR) in a multivariable model. The median dose to the inner quadrants of the contralateral breast was 1.70 Gy; to the areola, 1.20 Gy; and to the outer quadrants, 0.72 Gy. Ninety-two percent of patients received ≥1 Gy to the inner quadrants. For each calendar year of diagnosis, dose declined significantly for each location, most rapidly for the inner quadrants (0.04 Gy/year). Declines in dose were similar across subgroups defined by age at diagnosis and body mass index. The PAR for CBC due to radiation exposure >1 Gy for women <40 years of age was 17%. Radiation dose-reduction measures have reduced dose to the contralateral breast during breast radiation therapy. Reducing the dose to the contralateral breast to <1 Gy could prevent an estimated 17% of subsequent radiation-associated CBCs for women treated under 40 years of age. These dose estimates inform CBC surveillance for the growing number of breast cancer survivors who received radiation therapy as young women in recent decades. Continued reductions in dose to the contralateral breast could further reduce the incidence of radiation-associated CBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive breast cancer patients undergoing up-front surgery on their outcomes. Survival was not adversely affected by pN0(i+) and pN1mi in 1771 HER2-positive patients. However, in the case of pT1a-b HER2-positive breast cancers, a negative impact on recurrence-free survival was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without adjuvant chemotherapy. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based adjuvant chemotherapy for these patients. (1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5–64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04–5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03–6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients. [ABSTRACT FROM AUTHOR]

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before 99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8–96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies. [ABSTRACT FROM AUTHOR]

Purpose: According to ASTRO and ESTRO guidelines, external beam Partial Breast Irradiation (PBI) is a valid option for early-stage breast cancer patients. Nevertheless, there is lack of consensus about the best treatment schedule. Methods: We retrospectively analysed data of female patients treated at our institution from 2013 to 2022 with adjuvant "one-week" partial breast irradiation. Clinical Target Volume (CTV) was an isotropic expansion of 15 mm from the tumour bed (identified as the breast tissue between surgical clips). The treatment schedule was 30 Gy delivered with Volumetric Modulated Arc Therapy in 5 daily fractions. The primary endpoint was Local Control (LC). Disease-Free Survival (DFS), Overall Survival (OS) and safety were secondary endpoints. Results: Three hundred and forty-four patients with a median age of 69 (33–87) years were included in the study. After a median follow-up of 34 (7–105) months, 7 patients (2.0%) developed a local recurrence. Three-year LC, DFS and OS actuarial rates were 97.5% (95% CI 96.2%–98.8%), 95.7% (95% CI 94.2%–97.2%), and 96.9% (95% CI 95.7%–98.1%), respectively. Ten (2.9%) patients experienced grade 2 late toxicities. Five (1.5%) patients reported late cardiac major events. Three (0.9%) late pulmonary toxicities were detected. One hundred and five (30.5%) patients reported fat necrosis. Good or excellent cosmetic evaluation following the Harvard Scale was reported in 252 (96.9%) cases by the physicians, while in 241 (89.2%) cases by the patients. Conclusion: "One-week" PBI is effective and safe, and this schedule is a valid option for highly selected early breast cancer patients. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy after breast-conserving surgery has become an integral part of the treatment of breast cancer. In recent years, the development of radiotherapy technology has made great progress in this field, including the comparison of the curative effects of various radiotherapy techniques and the performance of the segmentation times. The choice of radiotherapy technology needs to be co-determined by clinical evidence practice and evaluated for each individual patient to achieve precision radiotherapy. This article discusses the treatment effects of different radiotherapy, techniques, the risk of second cancers and short-range radiation therapy techniques after breast-conserving surgery such as hypo fractionated whole breast irradiation and accelerated partial breast irradiation. The choice of radiotherapy regimen needs to be based on the individual condition of the patient, and the general principle is to focus on the target area and reduce the irradiation of the normal tissues and organs. Short-range radiotherapy and hypofractionated are superior to conventional radiotherapy and are expected to become the mainstream treatment after breast-conserving surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to avoid side effects from treatment, patients suffering from breast cancer with a lower risk of relapse might forgo radiation therapy to the whole breast or endocrine therapy after surgery. In this analysis, we compared these two options regarding the risk of breast cancer relapse with the help of direct trials and a network that analyzed one of the two options. We found that both treatment options have similar long-term cancer outcomes and should be considered equally effective. Background: Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. Methods: We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. Results: We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42–0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53–1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45–2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59–1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38–1.36; p = 0.305). Conclusion: Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches. [ABSTRACT FROM AUTHOR]

Background: We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. Methods: An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1–2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). Results: A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1–2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre–South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. Conclusions: Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations. [ABSTRACT FROM AUTHOR]

Purpose: To report outcomes on a subset of patients with triple negative breast cancer (TNBC) treated on prospective trials with post-lumpectomy partial breast irradiation and concurrent chemotherapy (PBICC) and compare them to a retrospectively assessed similar cohort treated with whole breast irradiation after adjuvant chemotherapy (WBIaC). Methods and materials: Women with T1-2, N0-1 invasive breast cancer with = 2mm lumpectomy margins were offered therapy on one of two PBICC trials. PBI consisted of 40.5 Gy in 15 daily 2.7 Gy fractions delivered concurrently with the first 2 cycles of adjuvant chemotherapy. The comparison cohort received WBI to a median dose of 60.7 Gy, (including boost, range 42.5 - 66 Gy), after completion of non-concurrent, adjuvant chemotherapy. We evaluated disease-free survival (DFS), and local/loco-regional/distant recurrence-free survival (RFS). We compared survival rates using Kaplan-Meier curves and log-rank test of statistical significance. Results: Nineteen patients with TNBC were treated with PBICC on prospective protocol, and 49 received WBIaC. At a median follow-up of 35.5 months (range 4.8-71.9), we observed no deaths in the PBICC cohort and 2 deaths in the WBIaC cohort (one from disease recurrence). With a median time of 23.4 (range 4.8 to 47) months, there were 7 recurrences (1 nodal, 4 local, 4 distant), all in the WBIaC group. At 5 years, there was a trend towards increased local RFS (100% vs. 85.4%, p=0.17) and loco-regional RFS (100% vs. 83.5, p=0.13) favoring the PBICC cohort. There was no significant difference in distant RFS between the two groups (100% vs. 94.4%, p=0.36). Five-year DFS was 100% with PBICC vs.78.9% (95% CI: 63.2 to 94.6%, p=0.08) with WBIaC. Conclusion: This study suggests that PBICC may offer similar and possibly better outcomes in patients with TNBC compared to a retrospective cohort treated with WBIaC. This observation is hypothesis-generating for prospective trials. [ABSTRACT FROM AUTHOR]

Breast cancer is a significant global health concern, and the discovery of endocrine therapy has played a crucial role in the treatment of estrogenpositive breast cancer. However, these therapies are often associated with osteoporosis-related adverse events, which increase the risk of fractures in breast cancer patients and can result in limited mobility and reduced quality of life. Previous studies have shown that osteoporosis is essential side effects of the breast cancer therapy, although the exact mechanisms remain mostly unclear. Current clinical treatments, such as bisphosphonates, cause side effects and may impact the therapeutic response to endocrine drugs. In this review, we explore the likelihood of endocrine therapy-induced osteoporosis in estrogen-positive breast cancer therapy and discuss the involved mechanisms as well as the therapeutic potential of drugs and drug combination strategies. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined. [ABSTRACT FROM AUTHOR]

Accumulating epidemiological studies have investigated a possible interconnection between migraine (Mi) and breast cancer (BC) because of the strong link between these diseases and female reproductive hormones. This review aims to consolidate findings from epidemiological studies and explore biologically plausible hypothetical mechanisms related to hormonal pathways. Current evidence suggests a protective role of Mi in BC development, particularly in case–control studies but not in cohort ones. The inconsistency among studies may be due to several reasons, including diagnostic criteria for Mi and the age gap between the development of these two diseases. Furthermore, recent research has challenged the concept of a net beneficial effect of Mi on BC, suggesting a more complex relationship between the two conditions. Many polymorphisms/mutations in hormone-related pathways are involved in at least one of the two conditions. The most promising evidence has emerged for a specific alteration in the estrogen receptor 1 gene (rs2228480). However, the possible specific mutation or polymorphism involved in this association has not yet been identified. Further studies with robust methodologies are needed to validate the protective role of Mi in BC and fully elucidate the precise nature of this causal relationship. [ABSTRACT FROM AUTHOR]

Background: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722). [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-induced heart disease represents a spectrum of early and late effects. It is a significant concern for cancer survivors who receive thoracic radiation therapy, as it is the most common nonmalignant cause of death in this population. Subclinical cardiac damage can be detected at an early stage after irradiation and may possibly be used to predict late cardiac complications. Modern radiotherapy techniques, such as deep inspiration breath-hold radiotherapy or intensity-modulated radiation therapy, can reduce the heart dose and probably do not cause alterations in myocardial perfusion. This paper describes the study protocol we will use to evaluate perfusion defects after left-sided breast radiotherapy using myocardial perfusion single-photon computed tomography. Breast radiotherapy can lead to radiation-induced cardiac disease, particularly in left breast cancers. Recent studies have shown that subclinical cardiac lesions, such as myocardial perfusion deficits, may occur early after radiotherapy. The primary method for irradiating breast cancer, known as opposite tangential field radiotherapy, can cause the anterior interventricular coronary artery to receive a high dose of radiation during left breast irradiation. To explore alternative approaches that could reduce the risk of myocardial perfusion defects in patients with left breast cancer, we plan to conduct a prospective single-center study using a combination of deep inspiration breath hold radiotherapy and intensity modulated radiation therapy. The study will use stress and, if necessary, resting myocardial scintigraphy to assess myocardial perfusion. The trial aims to show that reducing the cardiac dose with these techniques can prevent the appearance of early (3-month) and medium-term (6- and 12-month) perfusion disorders. [ABSTRACT FROM AUTHOR]

Purpose: The detection of human epidermal growth factor receptor 2 (HER2) expression status is essential to determining the chemotherapy regimen for breast cancer patients and to improving their prognosis. We developed a deep learning radiomics (DLR) model combining time-frequency domain features of ultrasound (US) video of breast lesions with clinical parameters for predicting HER2 expression status. Patients and Methods: Data for this research was obtained from 807 breast cancer patients who visited from February 2019 to July 2020. Ultimately, 445 patients were included in the study. Pre-operative breast ultrasound examination videos were collected and split into a training set and a test set. Building a training set of DLR models combining time-frequency domain features and clinical features of ultrasound video of breast lesions based on the training set data to predict HER2 expression status. Test the performance of the model using test set data. The final models integrated with different classifiers are compared, and the best performing model is finally selected. Results: The best diagnostic performance in predicting HER2 expression status is provided by an Extreme Gradient Boosting (XGBoost)-based time-frequency domain feature classifier combined with a logistic regression (LR)-based clinical parameter classifier of clinical parameters combined DLR, particularly with a high specificity of 0.917. The area under the receiver operating characteristic curve (AUC) for the test cohort was 0.810. Conclusion: Our study provides a non-invasive imaging biomarker to predict HER2 expression status in breast cancer patients. [ABSTRACT FROM AUTHOR]

Breast cancer and prostate cancer are sex hormone-dependent cancers, and estrogen or androgen suppression therapy is the standard treatment. Cancer treatment-induced bone loss (CTIBL): bone loss and osteoporosis have become important side effects of these therapies. To summarize the current evidences, (1) Endocrine therapy for breast cancer and prostate cancer is associated with a significant decrease in bone mineral density. (2) Aromatase inhibitors (AI) for breast cancer are associated with a significant increase in fractures, and androgen deprivation therapy (ADT) for prostate cancer is likely to be associated with an increase in fractures. (3) Administration of bisphosphonates and denosumab increases bone mass in patients undergoing endocrine therapy for breast cancer. Administration of bisphosphonates, denosumab, and SERMs increased bone mass in patients undergoing ADT therapy for prostate cancer. (4) Bisphosphonates and denosumab reduce fracture risk in patients on AI for breast cancer, and toremifene and denosumab in patients on ADT for prostate cancer. [ABSTRACT FROM AUTHOR]

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor. [ABSTRACT FROM AUTHOR]