Search

Simple Summary: Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is discussed. We evaluated the impact of cALND omission on survival in breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 BC, the non-SN involvement rate was 13.2%. With a median follow-up of 66.46 months, multivariate analysis showed that cALND omission was significantly associated with overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly impacted by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative patients, DFS, OS, RFS, and MFS were also significantly affected (HR: 2.358, 3.317, 2.538, 2.756). For 161 patients ≤ 50 years with ER-positive/Her2-negative BC, OS and BCSS were notably associated with cALND omission (HR: 103.47 and 50.874). These findings suggest a negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of HER2-inhibitors for the treatment of HER2-positive breast cancer represented a breakthrough in targeted tumor therapy. However, as for other targeted therapeutics, drug resistance remains a serious challenge to the treatment of HER2+ BC. Recent research has identified critical biomarkers for HER2-inhibitor resistance and explored more effective treatment regimens in HER2+ breast cancer to overcome drug resistance; however, research on several potential biomarkers and promising alternative therapies remains incomplete. HER2 (human epidermal growth factor receptor 2) is highly expressed in a variety of cancers, including breast, lung, gastric, and pancreatic cancers. Its amplification is linked to poor clinical outcomes. At the genetic level, HER2 is encoded by the ERBB2 gene (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), which is frequently mutated or amplified in cancers, thus spurring extensive research into HER2 modulation and inhibition as viable anti-cancer strategies. An impressive body of FDA-approved drugs, including anti-HER2 monoclonal antibodies (mAbs), antibody–drug conjugates (ADCs), and HER2-tyrosine kinase inhibitors (TKIs), have demonstrated success in enhancing overall survival (OS) and disease progression-free survival (PFS). Yet, drug resistance remains a persistent challenge and raises the risks of metastatic potential and tumor relapse. Research into alternative therapeutic options for HER2+ breast cancer therefore proves critical for adapting to this ever-evolving landscape. This review highlights current HER2-targeted therapies, discusses predictive biomarkers for drug resistance, and introduces promising emergent therapies—especially combination therapies—that are aimed at overcoming drug resistance in the context of HER2+ breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is a challenging form of breast cancer known for its aggressive nature and limited treatment options. The DESTINY-Breast 04 trial has demonstrated improved survival outcomes in metastatic human epithelial growth factor receptor 2 (HER2)-low breast cancer patients treated with trastuzumab-deruxtecan (T-Dxd). Since the potential proportion of breast cancer patients that may benefit from these novel agents are reported to be around 39% to 79%, investigating the role of HER2-low has been a topic of interest. By analyzing the outcomes of over 2500 patients, we discovered that those with HER2-low TNBC typically experience better survival rates than HER2-0 TNBC. This difference was especially significant in postmenopausal women. These findings suggest a potential re-evaluation of how TNBC is classified and treated, highlighting the importance of identifying HER2-low expression for improving personalized treatment strategies and patient care. TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer remains a burden for women worldwide. Among the factors that contribute to breast cancer development is estrogen exposure during one's lifetime, both endocrine and exocrine. Polymorphisms in KEAP1-NRF2 complex, the master regulator of oxidative stress metabolism, have been correlated with a poorer outcome. The aim of our study was to identify and correlate polymorphisms in this complex, in breast cancer tissue, benign surrounding tissue and in peripheral blood. We verified a tendency towards the loss of heterozygosity in the benign surrounding tissue when compared to blood and to tumour tissue. Correlating with clinical data, histologic grade 2 has a higher variability of genotypes. The results indicate a heterogeneous and active microenvironment. Therefore, clinical approaches would benefit from the evaluation of somatic mutations in this complex. Moreover, further studies should be developed in order to evaluate the predictive value of the histologic grades, taking into consideration the genetic profile. Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant treatment is an increasingly used treatment option for patients with both advanced and early-stage breast cancer to achieve downstaging and to improve prognosis. Therefore, it is important to evaluate its role in the multidisciplinary management of breast cancer patients and its effects on surgical outcomes and disease-free and overall survival. Achieving a pathologic complete response seems to improve disease-free and overall survival and even a partial response can be useful as an in-vivo chemosensitivity test for tailored adjuvant therapy. Clinical features, histology, and immunohistochemical findings play a role in achieving a pathological response. Therefore, they should be thoroughly investigated beforehand to better evaluate the treatment burden–benefits ratio and to predict the response. The correlation between TNM staging and histology variations in a sample of patients who underwent neoadjuvant chemotherapy demonstrates a positive impact on both increasing conservative surgery and achieving pCR, resulting in better outcomes in terms of disease-free survival (DFS) and the risk of relapse. Benefits have also been highlighted in terms of cosmetic outcomes, postoperative complications, and psychological benefits. However, the overall outcomes must be evaluated according to the subtype and individual characteristics of the patients. [ABSTRACT FROM AUTHOR]

Background: Palliative care improves cancer patients' quality of life. Limited research has investigated racial/ethnic disparities in palliative care utilization and its associated survival among metastatic breast cancer (MBC) patients. Objectives: To examine racial/ethnic palliative care use disparities and assess racial/ethnic overall survival differences in MBC patients stratified by palliative care use. Design: A retrospective study of MBC patients from the 2004–2020 National Cancer Database. Measurements: Palliative care was defined as noncurative cancer treatment, including surgery, radiotherapy, systemic therapy, and/or pain management; utilization was coded "yes/no." Racial/ethnic groups included Asian, American Indian or Alaska Native (AIAN), Black, Hawaiian or Other Pacific Islander (HPI), Hispanic, and White. Logistic regression was performed to assess palliative care use disparities. Overall survival was modeled using Cox regression. Results: Of 148,931 patients, the mean age was 62 years; 99% were female; 73% identified as White, 17% as Black, 6% as Hispanic, 3% as Asian, 0.3% as AIAN, and 0.3% as HPI; 42% and 39% had Medicare and private insurance, respectively. Overall, 21% used palliative care, with an increasing utilization rate from 2004 to 2020 (3.6% increase per year, p-trend <0.001). Black (adjusted odds ratio [aOR] = 0.89; 95% confidence interval [CI]: 0.84 to 0.94), Asian (aOR = 0.76; 95% CI: 0.68 to 0.86), and Hispanic (aOR = 0.68; 95% CI: 0.62 to 0.74) patients had a lower likelihood of palliative care utilization than White patients. Among palliative care users, compared with White patients, Black (adjusted hazard ratio [aHR] = 1.14, 95% CI: 1.07 to 1.21) patients had a greater mortality risk, while Asian (aHR = 0.83, 95% CI: 0.71 to 0.97) and Hispanic (aHR = 0.77, 95% CI: 0.69 to 0.87) patients had a lower mortality risk. Conclusions: Palliative care utilization among MBC patients significantly increased but remained suboptimal. Racial/ethnic minority patients were less likely to use palliative care, and Black patients had worse survival, than White patients, suggesting the need for improving palliative care access and ameliorating disparities in MBC patients. [ABSTRACT FROM AUTHOR]

Evidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. A retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients' age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. 56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0–132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3–28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5–158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. There are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities. • This study reported SABR treatment outcomes for multisite OM and OP diseases originating from metastatic breast cancer • It showed modest local control and post-treatment toxicities on the SABR of extracranial OM and OP from metastatic breast cancer. • The types of follow-up imaging, OM vs OP, oestrogen receptor status, and number of metastases for SABR can be used as PFS prognostic factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Hereditary breast cancer represents a significant proportion of breast cancer cases worldwide, and BRCA1 and BRCA2 explain the majority of these. Less frequent genes with variable penetrance remain less characterized in Colombia. This study explores the characteristics and outcomes of 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Instituto Nacional de Cancerología, Colombia (INC-C) from 2018 to 2021 as part of an Institutional Hereditary Cancer Program implementation. We described the distribution of germline PVs among the different breast cancer molecular subtypes in this cohort of carriers. We observed that most PVs were in known breast cancer susceptibility genes, and PVs in BRCA2 were the most frequent. Notably, we observed that patients with disease progression were predominantly carriers of PVs in the BRCA2 gene. This study aimed to investigate prognosis and survival differences in 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Breast Unit of the Instituto Nacional de Cancerología, Colombia (INC-C) between 2018 and 2021. Median age at diagnosis was 46 years, with 62.2% presenting locally advanced tumors, 47.6% histological grade 3, and 35.4% with triple-negative breast cancer (TNBC) subtype. Most carriers, 74.4% (61/82), had PVs in known breast cancer susceptibility genes (i.e., "associated gene carriers" group, considered inherited breast cancer cases): BRCA2 (30), BRCA1 (14), BARD1 (4), RAD51D (3), TP53 (2), PALB2 (2), ATM (2), CHEK2 (1), RAD51C (1), NF1 (1), and PTEN (1). BRCA1-2 represented 53.7%, and homologous recombination DNA damage repair (HR-DDR) genes associated with breast cancer risk accounted for 15.9%. Patients with PVs in non-breast-cancer risk genes were combined in a different category (21/82; 25.6%) (i.e., "non-associated gene carriers" group, considered other breast cancer cases). Median follow-up was 38.1 months, and 24% experienced recurrence, with 90% being distant. The 5-year Disease-Free Survival (DFS) for inherited breast cancer cases was 66.5%, and for other breast cancer cases it was 88.2%. In particular, for carriers of PVs in the BRCA2 gene, it was 37.6%. The 5-year Overall Survival (OS) rates ranged from 68.8% for those with PVs in BRCA2 to 100% for those with PVs in other HR-DDR genes. Further studies are crucial for understanding tumor behavior and therapy response differences among Colombian breast cancer patients with germline PVs. [ABSTRACT FROM AUTHOR]

Accurate survival prediction is a critical goal in the prognosis of breast cancer patients because it can help physicians make more patient-friendly decisions and further guide appropriate treatment. Breast cancer is often caused by genetic abnormalities, which prompts researchers to consider information such as gene expression and copy number variation in addition to clinical data in their studies. The integration of these multi-modal data can improve the predictive power of models. However, with the highly unbalanced information of breast cancer patient data, it becomes a new challenge for breast cancer patient survival prediction to fully extract the characteristic information of these multi-modal data and to consider the complementarity of this information. To this end, we propose a deep multi-modal fusion network (DMMFN) to predict the five-year survival of breast cancer patients by integrating clinical data, copy number variation data, and gene expression data. The imbalanced dataset is first processed using the oversampling method SMOTE-NC. Then the abstract modal features of the multi-modal data are extracted by the two-layer one-dimensional convolutional neural network and the bi-directional long short-term memory network. Next, the weight coefficients of each modal data are dynamically adjusted using gated multimodal units to obtain fusion features. Finally, the fusion features are fed into the MaxoutMLP classifier to obtain the final prediction results. We conducted experiments on the METABRIC dataset to verify the validity of the multi-modal data and compared it with other methods. The comprehensive performance evaluation shows that DMMFN has better prediction performance. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic triple-negative breast cancer is an aggressive cancer with an average survival of 8 to 13 months. However, survival varies significantly among patients. We studied a large group of women in the National Cancer Database to better understand these survival differences. We found that the key factors influencing survival were comorbidity score (overall health status), histology (cancer subtype), number of metastatic sites (extent of cancer spread), and whether or not they received chemotherapy or immunotherapy. Our study's findings can help better predict survival based on an individual's specific factors and guide treatment strategies. Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan–Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials. [ABSTRACT FROM AUTHOR]

Purpose. Breast cancer is a heterogeneous disease. Exploring new prognostic and therapeutic targets in patients with breast cancer is essential. This study investigated the expression of MET, ESR1, and ESR2 genes and their association with clinicopathologic characteristics and clinical outcomes in patients with breast cancer. Methods. The METABRIC dataset for breast cancer was obtained from the cBioPortal public domain. Gene expression data for MET, ESR1, and ESR2, as well as the putative copy number alterations (CNAs) for MET were retrieved. Results. The MET mRNA expression levels correlated inversely with the expression levels of ESR1 and positively with the expression levels of ESR2 (r = −0.379, p < 0.001 and r = 0.066, and p = 0.004 , respectively). The ESR1 mRNA expression was significantly different among MET CNAs groups p < 0.001 . Patients with high MET/ESR1 coexpression had favorable clinicopathologic tumor characteristics and prognosticators compared to low MET/ESR1 coexpression in terms of greater age at diagnosis, reduced Nottingham Prognostic Index, lower tumor grade, hormone receptor positivity, HER2-negative status, and luminal subtype p < 0.001 . In contrast, patients with high MET/ESR2 coexpression had unfavorable tumor features and advanced prognosticators compared to patients with low MET/ESR2 coexpression p < 0.001 . No significant difference in overall survival was observed based on the MET/ESR coexpression status. However, when data were stratified based on the treatment type (chemotherapy and hormonal therapy), survival was significantly different based on the coexpression status of MET/ESR. Conclusions. Findings from our study add to the growing evidence on the potential crosstalk between MET and estrogen receptors in breast cancer. The expression of the MET/ESR genes could be a novel prognosticator and calls for future studies to evaluate the impact of combinational treatment approaches with MET inhibitors and endocrine drugs in breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Although women 70 years of age and older represent a large percentage of newly diagnosed breast cancer cases, older individuals are drastically underrepresented in clinical trials. Most women diagnosed with breast cancer at 70 years of age and older present with hormone receptor-positive (HR+) breast cancer. Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapy has become the standard of care for metastatic HR+ breast cancer. This study reports that metastatic breast cancer patients ≥70 years of age receiving CDK4/6 inhibitor-based treatment, particularly when combined with an aromatase inhibitor, experience prolonged progression-free survival but display no such prolongation in overall survival and report more frequent adverse effects to treatment. The reported findings can aid in the development of optimized treatments based on age and help older patients weigh treatment options. The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study. All patients receiving CDK4/6 inhibitor-based therapy that were ≥70 years of age (n = 111) displayed prolonged progression-free survival (27.6 months) as compared to patients <70 years of age (n = 209, 21.1 months, HR = 1.38, p < 0.05). Specifically, patients receiving a CDK4/6 inhibitor with an aromatase inhibitor who were ≥70 years of age (n = 79) displayed exceptionally prolonged progression-free survival (46.0 months) as compared to patients receiving the same treatment who were <70 years of age (n = 161, 21.8 months, HR = 1.71, p < 0.01). However, patients ≥70 years of age also experienced more frequent adverse responses to CDK4/6 inhibitor-based treatment leading to dose reduction, hold, or discontinuation than the younger cohort (69% and 53%, respectively). Treatment strategies that may decrease toxicity without affecting efficacy (such as dose titration) are worth further exploration. [ABSTRACT FROM AUTHOR]

Simple Summary: The two major histological subtypes of breast cancer are ductal and lobular cancers. Histology impacts the biological behavior of breast cancer, so it is imperative to study its influence on the overall survival of breast cancer patients. The existing literature reports conflicting conclusions regarding the impact that histology might have on survival, so we aimed to study a large sample of patient data obtained from the National Cancer Database to determine if histology and several other clinical factors have an impact on the survival of early-stage breast cancer patients who have T1–T2 tumors, are clinically node-negative and have no metastatic activity. These results may help clinicians better understand the behaviors of different subtypes of breast cancer and will help them take a more tailored approach to breast cancer treatment. Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1–T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan–Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77–0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) ranks as among the top two commonly diagnosed cancers in women worldwide. Triple-negative breast cancer (TNBC) is recognized globally as the most lethal subtype of BC, with patients often building resistance to conventional chemotherapy treatments. This study assesses the relationship between taxane-based chemotherapy resistance in BC and the oncoprotein epithelial membrane protein 2 (EMP2), with an emphasis on the aggressive TNBC group. Analyses of preclinical models and human tissue samples reveal that EMP2 may not only be used to predict patient response to taxanes but also serve as a therapeutic target for resistant disease. Our findings demonstrate a correlation between elevated EMP2 expression post-chemotherapy and reduced survival outcomes and reveal that targeting EMP2 in conjunction with chemotherapy yields a synergistic reduction in TNBC tumor volume. Thus, results shed light on a novel biomarker for guiding the personalized, targeted treatment of intractable and recurrent TNBC. Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors. [ABSTRACT FROM AUTHOR]

Women around the world are most frequently afflicted with breast cancer, and it is one of the most frequent causes of cancer death in females. Breast cancer is usually classified according to biomarker status, triple‐negative breast cancer (TNBC) represents a distinct subtype characterized by immunohistochemical findings that denote negativity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) on cancer tissue. It is more common in younger women than in other subtypes. As an invasive breast cancer subtype with a unique drug-resistant phenotype and metastatic burden, it has limited treatment options, and patients have a poor prognosis with high rates of local, distant recurrence and mortality, and there is still a lack of standardized treatment protocols for TNBC. In this review, we delve into the current treatment strategies for TNBC and explore the potential for new approaches and targets in the future. This trial is registered with NCT03997123. [ABSTRACT FROM AUTHOR]

OBJECTIVE Breast carcinoma (BC) is the most common cancer in women, and, in particular, some subtypes are established as suitable for immunotherapy strategies targeting immune checkpoints. Programmed cell death-1 (PD-1), as well as cytotoxic T lymphocyte-associated protein-4 (CTLA-4), has an important role in the tumor microenvironment to escape from the immune system. In this study, we examined the relationship of Programmed cell death-1 (PD-L1) expression with survival, recurrence, and other prognostic factors. METHODS This retrospective cohort comprised tissue microarray blocks of 391 cases examined at the same institute between 2000-2012. All cases were completely resected tumors, without neoadjuvant therapy, with more than 5 years of follow-up. Clinical follow-up and all pathologic parameters were recorded. PD-L1 immunohistochemistry (SP263) was applied, then staining details including density, percentage, and patterns were noted for tumor areas and immune cells. PD-L1 expression results were analyzed, and its relationship with prognostic parameters and survival was investigated. RESULTS PD-L1 expression was detected in 90 (24.8%) cases: 55 in only tumor-infiltrating lymphocytes (TILs), 35 in both tumor and TILs. Statistically, there was no significant relationship between PD-L1 expression and survival. However, high histologic grade, high scores in pleomorphism and mitosis, mild stromal reaction, dense immune cell infiltration, perineural invasion, absence of lymph node metastasis, negativity of ER and PR, HER2 expression, and high Ki-67 results had a significant relationship with PD-L1 expression. CONCLUSION Consistent with the literature, our results showed that PD-L1 expression in triple-negative and HER2 overexpressed types and in the presence of TILs is higher than in other breast cancers. [ABSTRACT FROM AUTHOR]

BACKGROUND: The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011 or Z11) trial demonstrated no survival advantage with completion axillary lymph node dissection (ALND) for patients with T1-2 breast cancer, 1 to 2 positive SLNs who received adjuvant chemoradiation therapy. More than 70% of the cohort had estrogen receptor (ER)+ tumors. There is paucity of data on the adherence rate to Z11, as well as a dearth of data on the applicability of Z11 for the different subtypes. We conducted a large hospital-based study to evaluate the adherence rate to Z11 based on subtypes. STUDY DESIGN: The National Cancer Database was queried to evaluate 33,859 patients diagnosed with T1-2, N1, and M0 breast cancer treated with lumpectomy with negative margins, and adjuvant chemoradiation therapy between 2012 and 2018. Patients were classified into 3 groups: (1) ER+/HER2-, (2) ER-/HER2-, and (3) HER2+ regardless of ER status. The revised Scope of the Regional Lymph Node Surgery 2012 was used to classify patients into those who underwent an SLN or ALND. Differences in use of ALND by subtypes were compared. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS). A p value of <0.05 was considered statistically significant. RESULTS: For ER+/human epidermal growth factor receptor 2 (HER2)-, ER-/HER2-, and HER2+ tumors, the rate of ALND was 43.6%, 50.2%, and 47.8%, respectively. The 5-year OS for SLN and ALND for the entire cohort was 94.0% and 93.1% (p = 0.0004); for ER+/HER2-, it was 95.4% and 94.7% (p = 0.04); for ER-/HER2-, it was 84.1% and 84.3% (p = 0.41); for HER2+, it was 94.2% and 93.2% (p = 0.20). Multivariable cox proportional hazard regression analysis demonstrated no significant survival differences between SLN and ALND (p = 0.776). CONCLUSIONS: Z11 is applicable for women with early N1 disease, regardless of subtypes. ALND did not confer a survival advantage over SLN. Despite this, up to 50% of patients who fit Z11 criteria continue to undergo ALND. [ABSTRACT FROM AUTHOR]

Objective: Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors. Data sources: We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer. Data summary: Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life. Conclusions: Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer patients whose tumor has already developed metastases are now living longer and longer in studies. These results are encouraging but must be viewed with caution because study participants are in most cases very special, i.e., they are younger or have fewer concomitant diseases than the average patient. For this reason, we analyzed all patients who were diagnosed with metastases between 1995 and 2022. The analysis showed that survival has also improved continuously in this real-world patient group. In a comparison of the periods 2018–2022 vs. 1995–2000, patients live about 1.5 years longer, a total of approximately 48 months. Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022. A total of 1610 patients with a median age of 63 years (23–100) were evaluated. In all, 82.9% had hormone-receptor-positive disease, and 23.8% were HER2-positive. Evaluation in time cohorts by initial MBC diagnosis date showed a continuous prolongation of median OS from 31.6 months (0.5–237.3+) (1995–2000) to 48.4 months (0.4–61.1+) (2018–2022) (p = 0.003). Univariable analyses showed a significant dependence on the time cohort of diagnosis, metastatic status at initial diagnosis, age at metastasis, hormone and HER2 status, general condition, metastasis localization, and the number of affected organs. A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years. [ABSTRACT FROM AUTHOR]

Pregnancy-associated breast cancer (PABC) is a rare type of gestational cancer. It poses a significant challenge in diagnosis and management, especially in Asian countries with limited resources. We carried out a systematic literature review and narrative synthesis to identify survival outcomes for women with PABC in Asia. We searched MEDLINE, PubMed, Cochrane Library and the reference lists of the included English language articles for those conducted between January 2010 and August 2022. The search terms were pregnancy-associated breast cancer, breast cancer AND pregnancy, survival of PABC and prognosis of PABC patients. PABC is defined as breast cancer diagnosed either during pregnancy or 1 year--5 years postpartum. This review included observational studies conducted in Asian countries. The final 11 articles met the selection criteria and were analysed. Five of the studies had high quality methods as assessed using the Joanna Briggs Institute (JBI) checklist. We reported study design, year of diagnosis, country, definition of PABC, control group, age of participants, median follow-up time, survival outcomes and pregnancy as prognostic factors. Only five studies reported that PABC patients had a poor overall or disease-free survival rate compared to the control. Pregnancy was a significant independent prognostic factor of breast cancer in only two studies. This review highlights that pregnancy has an unconfirmed association with breast cancer survival in Asia. Most studies that found a non-significant association had small samples, thus there is a need for large-scale multinational epidemiological studies in Asia to establish the survival outcomes in PABC patients. [ABSTRACT FROM AUTHOR]

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]

Introduction: Breast cancer (BC) is one of the commonest cancers among women worldwide. Differences regarding tumor biology, presentation, genetics, and molecular subtypes may contribute to the relatively poorer prognosis among younger women. Limited information exists regarding pathologic characteristics and long-term outcomes among this group. Methods: This retrospective cohort study included 695 BC patients diagnosed over a 10-year period and investigated the clinicopathological characteristics and long-term disease outcomes among patients diagnosed at age less than or equal to 40 years compared with older ones. Cox regression analysis was performed, and Kaplan-Meier curves were generated to assess overall survival (OS). Results: Compared with the younger patients (⩽40 years) estrogen receptor (ER) and progesterone receptor (PR) expression was mainly positive in older patients (>40 years) (76.2% vs 61.3% and 64.2% vs 49.6%, respectively). The most common molecular subtype in both age groups was luminal B (44.1% in older and 40.3% in younger). A clinical complete remission after neoadjuvant therapy was observed more frequently in older patients (76.7%; N = 442) in comparison with the younger patients (66.4%; N = 79) (P =.018). Recurrence and disease progression were significantly more likely to occur among younger patients accounting for 12.6% and 29.4% of the cases, compared with 6.3% and 18.2% in older patients (P =.016 and P =.006, respectively). The overall mortality was 132 (19%) of 695, with 88% cancer-related deaths. Estrogen receptor and PR expression (P ⩽.001 and P =.003, respectively), molecular subtype (P =.002), tumor grade (P =.002), and N stage (P =.038) were the variables that were found to be significantly influenced by age. The OS was not statistically different among 2 age groups, but younger patients with luminal A molecular subtype showed significantly poor outcome (P =.019). Conclusion: Overall survival in women diagnosed with BC at age less than or equal to 40 years is not significantly worse than older patients. However, among patients with luminal A subtype, younger women had relatively poor survival. Further research is needed to understand this age-based disparity in outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Young women who develop breast cancer before the age of 40 often harbor a pathogenic germline variant in the BRCA1 or BRCA2 gene. The type of affected gene is associated with the expression of the clinical subtype, which in turn is associated with prognosis. To assess prognosis in young women with breast cancer, both aspects need to be considered. This retrospective, single-center cohort study describes survival outcomes in interaction with the aforementioned factors. The results indicate better overall survival in young triple-negative patients with pathogenic germline variants in BRCA1 or BRCA2 compared to triple-negative breast cancer without pathogenic variants, but not for other clinical subtypes. Data are scarce on the role of pathogenic germline variants in BRCA1 and BRCA2 (gBRCAm) in subtype-specific survival in young women who develop breast cancer under the age of 40. This retrospective, real-world cohort study assessed the distant disease-free survival (DDFS) and overall survival (OS) of young women diagnosed with breast cancer between 2008 and 2019 while taking into consideration the interaction of clinical subtypes and the gBRCA status. Among 473 women, HR+/Her2− was the most common subtype (49.0%), followed by TNBC (31.3%), HR+/Her2+ (13.7%), and Her2+/HR− (5.9%). The gBRCA status was known for 319 cases (gBRCAwt (wild-type – without pathogenic variants in BRCA1 or BRCA2): 204, gBRCA1m: 83, gBRCA2m: 31, 1 patient with both). The distribution of clinical subtypes varied depending on the gBRCA status (p < 0.001). In survival analysis with a median follow-up of 43 months, the unadjusted DDFS and OS were worse for gBRCAwt TNBC compared to both HR+ subtypes, but not for gBRCAm TNBC patients. T-stage, nodal involvement, and the gBRCA status were identified as significant for survival in TNBC. In TNBC, gBRCAm was associated with better DDFS and OS than gBRCAwt (5-year DDFS 81.4% vs. 54.3%, p = 0.012 and 5-year OS 96.7% vs. 62.7%, p < 0.001). In contrast, in HR+/Her2− patients, gBRCAm patients showed a tendency for worse survival, though not statistically significant. Subtype-specific survival in young women with breast cancer needs to be evaluated in interaction with the gBRCA status. For TNBC, gBRCAm is of favorable prognostic value for overall survival, while patients with gBRCAwt TNBC need to be considered to have the highest risk for adverse survival outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: While tumor-associated macrophages (TAMs) are known to be associated with a poor prognosis in breast cancer (BC) in general, how they influence different BC subtypes has remained poorly studied. Here, we investigated the prognostic value of M2-like TAMs (CD163+) that mediate several pro-tumoral functions, and all TAMs (CD68+) in a patient cohort of 278 non-metastatic BC cases, half of which were HER2+. Our results indicate that M2-like TAMs were associated with a poor outcome in HER2+ BC, in which a high CD163+ TAM count was independently associated with an inferior outcome regardless of hormone receptor status and the use of adjuvant trastuzumab. In summary, our results suggest that the prognostic value of M2-like TAMs is especially significant in HER2+ BC; these patients might benefit from combination treatments that include therapies targeting macrophage function. Tumor-associated macrophages (TAMs) are associated with a poor outcome in breast cancer (BC), but their prognostic value in different BC subtypes has remained somewhat unclear. Here, we investigated the prognostic value of M2-like TAMs (CD163+) and all TAMs (CD68+) in a patient cohort of 278 non-metastatic BC patients, half of whom were HER2+ (n = 139). The survival endpoints investigated were overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). In the whole patient cohort (n = 278), a high CD163+ TAM count and a high CD68+ TAM count were associated with a worse outcome (p ≤ 0.023). In HER2+ BC, a high CD163+ TAM count was an independent factor for a poor prognosis across all the investigated survival endpoints (p < 0.001). The prognostic effect was evident in both the HER2+/hormone receptor-positive (p < 0.001) and HER2+/hormone receptor-negative (p ≤ 0.012) subgroups and regardless of the provision of adjuvant trastuzumab (p ≤ 0.002). In HER2-negative BC, the CD163+ TAM count was not significantly associated with survival. These results suggest that a high CD163+ TAM count predicts an inferior outcome, especially in HER2+ BC patients, and as adjuvant trastuzumab did not overcome the poor prognostic effect, combination treatments including therapies targeting the macrophage function could represent an effective therapeutic approach in HER2+ BC. [ABSTRACT FROM AUTHOR]

Simple Summary: In clinical practice, human epidermal growth factor receptor (HER2)-negative tumors include triple-negative or luminal breast cancer. HER2-negative breast cancer can be further characterized by immunohistochemical (IHC) and in situ hybridization (ISH) scores into HER2 IHC0 or HER2-low (IHC 1+, 2+/ISH−. Interest in HER2-low tumors has increased as data show the efficacy of HER2-targeted therapies in this subgroup. While several studies have examined treatment variations in the overall breast cancer population, there is limited information on the real-world treatment patterns among patients with HER2 (IHC0/-low) metastatic or recurrent breast cancer. Our study addresses this gap by analyzing treatment and outcomes by HER2 status and found that outcomes were similar in the HER2 IHC0 and -low groups. Our findings add value to the general understanding of the clinical differences between HER2 IHC0/-low and de novo/recurrent disease and have important implications for new effective treatment strategies designed for varying levels of HER2 expression. Improved understanding of the biological heterogeneity of breast cancer (BC) has facilitated the development of more effective and personalized approaches to treatment. This study describes real-world evidence on treatment patterns and outcomes for a population-based cohort of patients with human epidermal growth factor receptor (HER2) IHC0 and -low BC with de novo or recurrent disease from Alberta, Canada. Patients 18+ years old diagnosed with HER2 IHC0/-low, de novo/recurrent BC from 2010 to 2019 were identified using Alberta's cancer registry. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to examine patient characteristics, treatment patterns, and survival outcomes. A total of 3413 patients were included in the study, of which 72.10% initiated first line hormonal and non-hormonal systemic therapy. The 1-year overall survival (OS) was 81.09% [95% CI, 79.52–82.69]. Recurrent patients had a higher OS compared to de novo patients: 54.30 months [95% CI, 47.80–61.90] vs. 31.5 months [95% CI, 28.40–35.90], respectively. Median OS was 43.4 months [95% CI, 40.70–47.10] and 35.80 months [95% CI, 29.00–41.70] among patients with HER2-low and HER2 IHC0 cancer, respectively. The study results provide real-world evidence regarding the clinical outcomes of HER2 IHC0/-low and de novo/recurrent disease. [ABSTRACT FROM AUTHOR]

Simple Summary: This narrative review discusses the role of tertiary lymphoid structures (TLSs) in breast cancer. TLSs are ectopic lymphoid formations that can develop in response to inflammatory signals. They are present in about 60% of breast cancer cases and are particularly common in the triple-negative subtype. TLS presence is linked to better outcomes, and they could serve as prognostic and predictive markers for treatment response. Additionally, TLS-positive tumors may show improved outcomes regardless of other factors like PDL-1 expression or TILs. The emergence of TLS as a potential therapeutic avenue highlights the importance of standardized pathology methods for their detection in cancer research. This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes). [ABSTRACT FROM AUTHOR]

OBJECTIVE The aim of the study was to evaluate the association between metabolic parameters obtained from pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and molecular subtype, immunohistochemistry, and overall survival (OS) in female breast cancer (BC) patients with invasive ductal carcinoma (IDC). METHODS A total of 179 patients were included in the study, and their primary tumor histopathological features, molecular subtypes, axillary lymph node (ALN) involvement, distant metastasis, and OS were evaluated and compared 18F-FDG PET parameters. Among the PET parameters, maximum standardized uptake value (SUVmax), mean SUV, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor and ALNs were examined. RESULTS Based on molecular subtypes, the metabolic parameters of tumors were at their lowest in the Luminal A group and had the highest values within the triple-negative BC group. The triple-negative BC subtype was associated with a higher Ki67 proliferation index. Tumor SUVmax was higher in patients who were estrogen receptor negative, progesterone receptor (PR) negative, had nuclear grade III, and had distant metastasis (p=0.021, p=0.001, p<0.001, p=0.014, respectively). Patients with distant metastasis, ALN metastasis, and internal mammary lymph node involvement had higher tumor TLG and MTV (respectively, p<0.001, p<0.001, p<0.001). Higher ALN SUVmax values were observed in patients with distant metastasis and those who were PR negative (p=0.016). The ALN TLG value was found to be higher in patients with distant metastases and ALN metastases compared to those without (p<0.001, p=0.049, p=0.025, respectively). CONCLUSION The study indicates that PET/CT is a highly dependable method for detecting ALN involvement. Furthermore, assessing metabolic tumor characteristics using 18F-FDG PET/CT before initiating primary IDC treatment might provide crucial diagnostic and prognostic insights that significantly contribute to managing the disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST. STUDY DESIGN: We conducted a single-institution, retrospective study of 521 patients with cN2--3 primary nonmetastatic breast cancer treated with NST followed by surgery and radiation from 2012 to 2018. Descriptive statistics, multivariate Cox regression, and Kaplan--Meier analyses were performed. RESULTS: The mean age was 50.5 years, and median follow-up was 61 (4.7 to 197) months. The majority of patients had hormone receptor--positive (HR+)/HER2-negative tumors (HER2-; n = 242, 47.8%). Most were cT2 (n = 243; 46.6%) or cT3 (n = 139; 26.7%) and 73.3% (n = 382) had cN3 disease. Rate of axillary pCR was 34.2%, and breast and axillary pCR was 19.4% (n = 101). Event-free survival (EFS) at 5 years was 75.1% (95% CI, 0.71 to 0.79). Rate of locoregional recurrence was 6.7%; distant metastatic rate was 29.4%. Axillary pCR with or without breast pCR was significantly associated with longer EFS (p = 0.001). Achieving breast/axillary pCR was an independent predictor of improved EFS (hazard ratio 0.22, p < 0.0001). Having triple-negative disease was associated with worse EFS (hazard ratio 1.74, p = 0.008). CONCLUSIONS: In a high-risk cohort of patients with cN2--3 disease, trimodality therapy was effective in achieving durable EFS. Approximately one-third of patients achieved axillary pCR, which was associated with improved survival. Further studies are needed to accurately determine axillary response in cN2--3 breast cancer after NST in order to develop de-escalation strategies to reduce morbidity associated with axillary surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: There is paucity of data on the optimal management of brain metastases in older women ≥65 years old with breast cancer. In this single-institutional retrospective study, we assessed the survival outcomes and treatment patterns of breast cancer patients ≥65 years old with brain metastases and compared them to younger patients. A total of 112 patients were included. Treatment-related adverse events were similar in both groups. Although older women had a poorer median overall survival compared to younger women (9.5 vs. 14.5 months), survival was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and leptomeningeal disease in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with brain metastases and personalized decision-making including a comprehensive geriatric assessment should be considered. Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan–Meier estimates and Cox proportional hazard regression method were used for survival analyses. Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65–84) compared to 52 years (31–64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is associated with poor overall survival (OS) in breast cancer patients; however, the most predictive nutritional indicators for the prognosis of patients with breast cancer are not well-established. This study aimed to compare the predictive effects of common nutritional indicators on OS and to refine existing nutritional indicators, thereby identifying a more effective nutritional evaluation indicator for predicting the prognosis in breast cancer patients. Methods: This prospective study analyzed data from 776 breast cancer patients enrolled in the "Investigation on Nutritional Status and its Clinical Outcome of Common Cancers" (INSCOC) project, which was conducted in 40 hospitals in China. We used the time-dependent receiver operating characteristic curve (ROC), Kaplan–Meier survival curve, and Cox regression analysis to evaluate the predictive effects of several nutritional assessments. These assessments included the patient-generated subjective nutrition assessment (PGSGA), the global leadership initiative on malnutrition (GLIM), the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI). Utilizing machine learning, these nutritional indicators were screened through single-factor analysis, and relatively important variables were selected to modify the PNI. The modified PNI, termed the cholesterol-modified prognostic nutritional index (CPNI), was evaluated for its predictive effect on the prognosis of patients. Results: Among the nutritional assessments (including PGSGA, GLIM, CONUT, NRI, and PNI), PNI showed the highest predictive ability for patient prognosis (time-dependent ROC = 0.58). CPNI, which evolved from PNI, emerged as the superior nutritional index for OS in breast cancer patients, with the time-dependent ROC of 0.65. It also acted as an independent risk factor for mortality (p < 0.05). Moreover, the risk of malnutrition and mortality was observed to increase gradually among both premenopausal and postmenopausal age women, as well as among women categorized as non-overweight, overweight, and obese. Conclusions: The CPNI proves to be an effective nutritional assessment tool for predicting the prognosis of patients with breast cancer. [ABSTRACT FROM AUTHOR]

Ribociclib in combination with endocrine therapy (ET) is a globally approved treatment option for patients with hormone receptor‐positive (HR+)/human epidermal growth factor receptor 2‐negative (HER2−) advanced breast cancer (ABC) and has demonstrated significantly improved overall survival (OS) in 3 phase 3 clinical trials. To justify the dose regimen and dose modification scheme for patients with ABC, the pharmacokinetic (PK), safety, and efficacy data of ribociclib were analyzed. The data of several phase 1‐3 clinical studies were pooled and analyzed to characterize the relationship between exposure (dose or PK) and efficacy (progression‐free survival (PFS), time to response, and OS) or safety (neutropenia and QT interval prolongation). The exposure–efficacy analysis showed no apparent relationship between ribociclib exposure and efficacy (PFS and OS), and efficacy analysis by dose reduction showed that patients with ABC continued to benefit from the treatment following dose reduction, supporting the starting dose of 600 mg as well as dose reductions to 400 and 200 mg. The exposure–safety analysis showed that neutropenia and QT prolongation are related to ribociclib exposure that can be effectively managed by individualized dose modification (dose reduction/interruption). Collective evidence from the exposure–response analyses for efficacy and safety support the use of ribociclib in combination with ET partners at the starting dose of 600 mg, and also the effectiveness of individualized dose reductions in managing safety, while maintaining efficacy, in patients with HR+/HER2− ABC. This analysis illustrates the utility of quantitative assessment in justifying dose selection and dose modification for oncology medicines. [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]

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to develop an innovative non-linear statistical model to predict clinical benefit in women with newly diagnosed breast cancer. A logistic generalized additive model was chosen as an innovative statistical approach, as opposed to conventional techniques. Clinical data, primary tumor (PT) features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and molecular subtype were considered for the purpose of the investigations. In this retrospective study of 70 women, higher primary tumor volume and metabolic parameters significantly compromised clinical benefit. A multivariate model for clinical benefit, incorporating age, body mass index, T, M, PT total lesion glycolysis, and PT volume, demonstrated excellent accuracy across the molecular subtypes. Our results emphasized the pivotal role of baseline FDG-PET/CT in predicting treatment outcomes. However, careful consideration is warranted when choosing the methodological approach for treatment outcome prediction, as non-linear influences of predictive biomarkers on clinical benefit were unveiled. Objectives: We aimed to develop a novel non-linear statistical model integrating primary tumor features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), molecular subtype, and clinical data for treatment benefit prediction in women with newly diagnosed breast cancer using innovative statistical techniques, as opposed to conventional methodological approaches. Methods: In this single-center retrospective study, we conducted a comprehensive assessment of women newly diagnosed with breast cancer who had undergone a FDG-PET/CT scan for staging prior to treatment. Primary tumor (PT) volume, maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on PET/CT. Clinical data including clinical staging (TNM) but also PT anatomical site, histology, receptor status, proliferation index, and molecular subtype were obtained from the medical records. Overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) were assessed as endpoints. A logistic generalized additive model was chosen as the statistical approach to assess the impact of all listed variables on CB. Results: 70 women with newly diagnosed breast cancer (mean age 63.3 ± 15.4 years) were included. The most common location of breast cancer was the upper outer quadrant (40.0%) in the left breast (52.9%). An invasive ductal adenocarcinoma (88.6%) with a high tumor proliferation index (mean ki-67 expression 35.1 ± 24.5%) and molecular subtype B (51.4%) was by far the most detected breast tumor. Most PTs displayed on hybrid imaging a greater volume (12.8 ± 30.4 cm3) with hypermetabolism (mean ± SD of PT maximum SUVmax, SUVmean, MTV, and TLG, respectively: 8.1 ± 7.2, 4.9 ± 4.4, 12.7 ± 30.4, and 47.4 ± 80.2). Higher PT volume (p < 0.01), SUVmax (p = 0.04), SUVmean (p = 0.03), and MTV (<0.01) significantly compromised CB. A considerable majority of patients survived throughout this period (92.8%), while five women died (7.2%). In fact, the OS was 31.7 ± 14.2 months and PFS was 30.2 ± 14.1 months. A multivariate prediction model for CB with excellent accuracy could be developed using age, body mass index (BMI), T, M, PT TLG, and PT volume as predictive parameters. PT volume and PT TLG demonstrated a significant influence on CB in lower ranges; however, beyond a specific cutoff value (respectively, 29.52 cm3 for PT volume and 161.95 cm3 for PT TLG), their impact on CB only reached negligible levels. Ultimately, the absence of distant metastasis M displayed a strong positive impact on CB far ahead of the tumor size T (standardized average estimate 0.88 vs. 0.4). Conclusions: Our results emphasized the pivotal role played by FDG-PET/CT prior to treatment in forecasting treatment outcomes in women newly diagnosed with breast cancer. Nevertheless, careful consideration is required when selecting the methodological approach, as our innovative statistical techniques unveiled non-linear influences of predictive biomarkers on treatment benefit, highlighting also the importance of early breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: Tumor proliferation is a key prognostic factor in breast cancer, but the relationship between tumor proliferation and prognosis remains unclear. Aims and Objectives: To investigate the association between tumor proliferation and prognosis in breast cancer patients using a pathological analysis. Materials and Methods: A retrospective cohort study was conducted, including 100 breast cancer patients who underwent surgical resection between January 2021 and December 2022.Tumor proliferation was assessed using Ki-67 immunostaining and evaluated patient prognosis based on disease-free survival (DFS) and overall survival (OS). We performed statistical analyses to examine the association between tumor proliferation and prognosis. Results: Our results showed a significant correlation between tumor proliferation and prognosis in breast cancer patients. High Ki-67 expression was associated with shorter DFS and OS, while low Ki-67 expression was associated with longer DFS and OS. The difference in DFS and OS between high and low Ki-67 expression groups was statistically significant. Conclusion: Tumor proliferation is a valuable prognostic marker in breast cancer and could be used to guide treatment decisions. Our findings suggest that patients with high Ki-67 expression may benefit from more aggressive treatment options, while patients with low Ki-67 expression may be able to avoid unnecessary treatment and its associated side effects. The accurate assessment of tumor proliferation using Ki-67 immunostaining could potentially improve patient outcomes and reduce the burden of breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population. Methods: In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rsl0995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. Conclusion: ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results. [ABSTRACT FROM AUTHOR]

The benefit of stereotactic body radiotherapy (SBRT) in metachronous oligometastatic breast cancer (OMBC) has previously been described and its use in current clinical practice is established. The role of SBRT in the management of synchronous OMBC remains uncertain. The aim of this study was to compare outcomes of SBRT-treated synchronous OMBC with those of SBRT-treated metachronous OMBC. This was a retrospective analysis of consecutive extracranial OMBC patients treated with SBRT at a single institution between 2011 and 2022. Kaplan–Meier methods were used to calculate progression-free survival (PFS), overall survival, local control and distant control. Log-rank tests were used to test any differences. Cox regression was used for univariate and multivariate analyses to identify predictive factors. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. In total, 74 OMBC patients with 113 lesions were analysed. The median follow-up was 20 months (range 0–98). Seventy per cent of patients presented metachronously and 30% synchronously. 30 Gy in three fractions was most commonly prescribed, resulting in a median biologically effective dose (BED at α/β = 10) of 60 Gy (range 35.7–112.5 Gy). Forty-nine per cent of patients switched systemic therapy post-SBRT (median time to switch: 14 months, range 0–79). Two patients (2%) experienced grade 3 acute toxicities with no grade ≥4 toxicities. At 2 years overall survival was 92.4% and PFS 39.0%, local control 85.9% and distant control 37.0%. For metachronous and synchronous disease, respectively, 2-year local control rates were 86.5% and 85.8% and PFS rates were 35.3% and 48.3%. The median PFS of metachronous and synchronous disease were 18 months and 17 months, respectively (P = 0.86). Predictive factors on multivariate analysis were treated site for overall survival, change in systemic therapy post-SBRT for PFS and BED for local control. Our data confirm SBRT as a well-tolerated treatment for OMBC with excellent local control rates regardless of metachronous or synchronous presentation. There is no suggestion that survival outcomes are inferior for synchronous disease. Further prospective studies are required to validate this finding. • SBRT is a well tolerated treatment for OMBC. • SBRT outcomes in synchronous OMBC are comparable with those of metachronous OMBC. • SBRT achieves excellent local control in synchronous and metachronous OMBC. [ABSTRACT FROM AUTHOR]

We examined the role of receptor profiles and other prognostic factors in survival outcomes after stereotactic radiosurgery (SRS) for brain metastases in breast cancer patients, to help improve selection of candidates for SRS. We included 149 consecutive patients who received SRS between 2012 and 2019 at the University Hospital of Copenhagen, Rigshospitalet, Denmark. Overall survival (OS) following SRS was determined through the Kaplan–Meier method, while CNS progression-free survival (CNS-PFS) was determined through competing risk analysis. Prognostic factors for both OS and CNS-PFS were evaluated through uni- and multivariate Cox regression and Fine-Gray models, respectively. The proportional hazards assumptions were tested through Schoenfeld residuals, and non-proportionality was accounted for by the inclusion of time-dependent variables. Median OS was 14.8 months for the entire cohort and was as follows for the four receptor profiles: 33.3 months for ER+/HER2+ (ER: estrogen receptor, HER2: human epidermal growth factor receptor 2), 11.0 months for ER+/HER2−, 17.7 months for ER−/HER2+, and 5.3 months for ER−/HER2−. In the multivariate model, the ER−/HER2− receptor profile (hazard ratio (HR): 2.00, 95% confidence interval (CI): 1.09–3.67) and the presence of extracranial visceral metastases (HR: 2.90, 95% CI: 1.53–5.50) were associated with worse OS. The ER+/HER2+ receptor profile (HR: 0.43, 95% CI: 0.19–0.96) and 5+ lines of treatment (HR: 0.40, 95% CI: 0.20–0.82) were both associated with improved OS. For CNS-PFS, 5+ lines of treatment (sub-distributional hazard ratio (SHR): 2.88, 95% CI: 1.06–7.81) was associated with worse CNS-PFS, while extracranial visceral metastases (SHR: 0.54, 95% CI: 0.30–0.97) was associated with reduced risk of CNS progression – which is primarily due to patients with extracranial metastases dying before developing new CNS progression. Extracranial visceral disease and the ER−/HER2− receptor profile were associated with poor survival outcomes following SRS. [ABSTRACT FROM AUTHOR]

Background: Cyclin‐dependent kinases 4 and 6 inhibitors (CDK4/6i) have been shown to improve progression‐free survival (PFS) in patients with metastatic breast cancer (MBC) in randomized control trials. This study aimed to evaluate the efficacy and safety of CDK4/6i in patients with advanced breast cancer (ABC) in a clinical setting. Methods: Consecutive patients with ABC were treated between October 2019 and March 2023 at Taipei Tzu Chi Hospital, Taiwan. Patients who had received at least one dose of CDK4/6i were included in this retrospective study. The main outcome of this study was efficacy based on the treating physicians' assessments in terms of PFS, and overall survival (OS), as well as the factors associated with patient outcome. The secondary outcome was safety. Results: A total of 85 patients were included in the analysis, with a mean age of 66.8 years. After a median follow‐up of 16.1 months, the median PFS was 28.4 months (95% CI: 22.5–33.6) and the median OS could not yet be estimated. The most common adverse events (AE) were fatigue (50.8%), anorexia (45.9%), and leukopenia (44.7%). In multivariable analysis, treatment with CDK4/6i with any grade AE or response to treatment effect (CR/PR) was an independent predictor for longer PFS (hazard ratio [HR] = 0.27, 95% CI: 0.11–0.68; HR = 0.21, 95% CI: 0.06–0.67; p < 0.05). Conclusion: CDK4/6i administered in a real‐world setting exhibits a similar survival benefit with the clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with breast cancer, that has spread and does not respond to hormone treatment, are usually treated with chemotherapy. If one kind of chemotherapy fails, another kind is started. There are various options and different chemotherapies to choose, but currently there is no standard, which kind to use first. Our aim was to find out, whether starting with one chemotherapy is better than with the other. We have investigated all patients with metastatic breast cancer who have been treated with the two most frequently used kinds of chemotherapy ("taxanes" and "PLD") at the University Hospital Basel, Switzerland. We found that patients who have received taxanes first survived longer than patients who received PLD first. These results are astonishing and highly relevant to patients with breast cancer and their treating physicians. Because our study was backward-looking, we cannot rule out that our results are confounded by any unknown factors other than the kind of chemotherapy. This important question should be investigated in a prospective clinical trial. Background: Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited. Methods: We analyzed electronic records of all patients with Her2-negative MBC treated with either first-line PLD or first-line taxane and subsequent crossover at the University Hospital Basel between 2003 and 2021. The primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). We used the Kaplan–Meyer method and logrank test to compare time-to-event endpoints and the Fisher exact test to compare discrete variables. Results: We retrospectively identified 42 patients with Her2-negative MBC who have received either single-agent PLD or single-agent taxane as first-line chemotherapy with subsequent crossover, including 23 patients who received first-line PLD and 19 patients who received first-line taxane. Baseline characteristics were similar between treatment groups. Treatment sequence PLD–taxane was significantly inferior to taxane–PLD regarding all endpoints: median TTNC 4.9 vs. 9.9 months (p = 0.006), median OS 17.8 vs. 24.6 months (p = 0.05), median PFS 4.4 vs. 9.0 months (p = 0.005), and ORR 13% vs. 53% (p = 0.01). Conclusions: Here, we report a first retrospective head-to-head comparison of the treatment sequence PLD–taxane versus taxane–PLD in patients with MBC, showing a substantial advantage of using taxanes first, followed by PLD. An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation. [ABSTRACT FROM AUTHOR]

Background: Metastatic triple-negative breast cancer (mTNBC) is an aggressive subtype of breast cancer with poor survival. Currently, the literature lacks comprehensive real-world evidence on locally recurrent and mTNBC patients. To validate the optimal treatment for patients with mTNBC, real-world evidence in combination with data from clinical trials must be evaluated as complementary. Objectives: The objective of the study is to examine outcomes and treatment patterns of patients with advanced triple-negative breast cancer (TNBC) utilizing real-world data of patients from all oncology sites across Denmark. Design: This is a retrospective, non-interventional, multi-site, population-based observational study conducted across all oncology departments in Denmark. Methods: We included all women diagnosed with metastatic or locally recurrent TNBC from January 1, 2017, to December 31, 2019, using the national Danish Breast Cancer Group database. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in the first to third treatment line. Results: The study included 243 women diagnosed with metastatic or recurrent TNBC. The median OS (mOS) was 11.6 months after the first line of treatment, 6.5 months after the second line, and 6.5 months after the third line. De novo mTNBC was associated with shorter OS (mOS: 8.3 vs 14.2 months), and those with a relapse within 18 months of primary diagnosis had shorter OS than those with a relapse after 18 months (mOS: 10.0 vs 18.2). In the first line, taxane was the preferred choice of treatment for patients with de novo mTNBC, whereas capecitabine was preferred for patients with recurrent TNBC. Conclusions: This real-world, nationwide study demonstrated poor OS among patients with metastatic or recurrent TNBC, with a mOS of 11.6 months (95% CI, 9.9-17.3). Patients who presented with de novo mTNBC or who had a relapse of their breast cancer within 18 months of primary diagnosis had shorter OS. Registration: The study was registered and approved by the Danish Capital Regions research overview (P-2021-605). [ABSTRACT FROM AUTHOR]

Background: Breast neuroendocrine neoplasms represent a rare subtype of breast cancer which have not been well studied or characterised, particularly in the metastatic setting. Aim: To present clinicopathological characteristics, treatment and outcomes of a series of patients with metastatic neuroendocrine carcinoma of the breast and review the current literature. Methods: We performed a retrospective review to identify and describe patients with metastatic neuroendocrine carcinoma of the breast at our centre between 2011 and 2021. Medical records, pathology and imaging results were examined to evaluate the clinical and histopathological features as well as the treatment pathways and prognosis of these patients. Results: We present a series of seven female patients with metastatic neuroendocrine carcinoma of the breast, as defined by the World Health Organization classification, over a period of 10 years (2011–2021) from a single centre. Median age at diagnosis was 48 years (range 39–63). Six of seven tissue samples expressed synaptophysin and chromogranin and were also oestrogen and progesterone receptor positive; median Ki‐67 index was 50% (range 20–90%). All seven patients had demonstrated avidity on 18F‐FDG PET imaging, and the six who underwent 68Ga‐DOTATATE PET all had significant avidity. Treatment modalities and sequencing varied, but all patients received chemotherapy during their disease course. Six patients received three or more lines of treatment. Median overall survival was 31.8 months (range 3.7–108.6). Median progression‐free survival (PFS) with first‐line therapy for metastatic disease was 5.8 months (range 1.8–37.8). Conclusions: This series shows the use of multiple modalities in treating this disease, with different sequencing in different patients. Despite multiple modalities used in the first‐line setting, first‐line PFS remains short. Larger series and further molecular characterisation are required to aid clinicians in managing this condition and to guide optimal treatment sequencing to improve outcomes in this rare patient group. [ABSTRACT FROM AUTHOR]

Purpose: Outcomes of females with triple-negative breast cancer (TNBC) are rarely explored in adolescents and young adults (AYAs). We compared clinical and survival outcomes of Latin American AYAs (≤39 years) with middle-aged (40–59 years) and older (≥60 years) females with TNBC by cancer stage. Methods: We performed a single-center retrospective cohort study among treated females with cancer stages I–III diagnosed from 2000 to 2014 in Peru. We evaluated overall survival (OS) and event-free survival (EFS). Time-to-event methods were used for analyses. Results: Of 1582 females with TNBC, 350 (22%) were AYAs, 887 (56%) were middle-aged, and 345 (22%) were older women. Tumor size >5 cm, histological grade III, and brain metastasis were more common features in AYAs. AYAs were treated more frequently with neoadjuvant chemotherapy. With a median follow-up of 102 months, the 5-year OS/EFS for AYAs was 55%/53%, similar to middle-aged (54%/49%) and older females (56%/51%). AYAs were not at higher risk for decreased OS or EFS in the multivariable Cox analysis. Our findings remained consistent by cancer stage. Conclusion: Although Latin American AYAs with TNBC have more aggressive clinical features at diagnosis, survival outcomes were comparable with middle-aged and older women with TNBC, suggesting that age is not a risk factor for worse survival outcomes if treatment is given according to cancer stage. Our findings should be interpreted with caution given the lack of information on certain covariates such as comorbidities. Strategies for early detection in primary care and prompt referral for treatment initiation should be developed. [ABSTRACT FROM AUTHOR]

Simple Summary: A new subgroup of breast cancer patients with different survival outcomes, even before new treatment options have been approved, which can be easily differentiated immunohistochemically, has recently received great attention. The approval of trastuzumab deruxtecan in August 2022 by the Food and Drug Administration (FDA) for patients with HER2-low-positive metastatic pretreated breast cancer suggested a new breast cancer subtype; this implied new cohorts of patients with different overall survival outcomes and therefore different treatment needs and chances. Therefore, in our study, we examined whether we could retrospectively differentiate HER-0 and HER2-low-positive breast cancer patients treated with neoadjuvant chemotherapy in a long-term follow-up over 20 years. We observed the overall survival, disease-free survival, and pathological complete response rate. In our study, we observed the long-term survival outcomes investigated for HER2-0 and HER2-low-positive breast cancer patients who received neoadjuvant chemotherapy. Between 1998 and 2020, 10,333 patients with primary breast cancer were treated, including 1373 patients with HER2-0 or HER2-low-positive disease with neoadjuvant chemotherapy. Descriptive analyses were performed, and logistic regression models and survival analyses were calculated for disease-free survival (DFS) and overall survival (OS). Among the 1373 patients, 930 (67.73%) had HER2-low-positive and 443 (32.27%) had HER2-0 tumors. Patients with HER2-0 tumors had a significantly better pathological complete response, 29.25% vs. 20.09%, and pathological complete response/in situ, 31.97% vs. 24.08%, than patients with HER2-low-positive tumors (p < 0.001; p = 0.003), regardless of the hormone receptor (HR) status. No statistically significant differences were observed for the HR-positive (p = 0.315; p = 0.43) or HR-negative subgroups (p = 0.573; p = 0.931). DFS and OS were significantly longer for HR-positive, HER2-low-positive patients (log-rank p = 0.02; p = 0.012). OS was significantly longer for HR-negative, HER2-0 patients (log-rank p = 0.032). No significant DFS differences were found for the HR-negative cohort (log-rank p = 0.232). For the overall cohort, no significant differences were noted between HER2-low-positive and HER2-0 patients, either for DFS (log-rank p = 0.220) or OS (log-rank p = 0.403). These results show different survival outcomes for HER2-0 and HER2-low-positive tumors relative to HR status. These different cohorts can be identified using standardized immunohistochemistry, even retrospectively. [ABSTRACT FROM AUTHOR]

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P =.246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P =.357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P =.157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P =.013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Cortactin is overexpressed in several types of invasive cancers. However, the role of cortactin expression in breast cancer prognosis has not been sufficiently elucidated. Therefore, we investigated the clinicopathological significance of cortactin in breast cancer. Methods: Tissue microarrays were prepared from a cohort of 506 patients with breast cancer, and cortactin expression was evaluated using immunohistochemistry. The cortactin immunoreactivity score (IRS) was quantified as the product of the intensity score and the percentage of immunoreactive cells. Cortactin expression was classified as low or high using the IRS (IRS ≤ 4 as a cortactin-low value and IRS > 4 as a cortactin-high value). We compared cortactin expression and clinicopathological factors according to the molecular subtypes of breast cancer. Results: Of 506 breast cancer cases, 333 and 173 showed high and low cortactin expression, respectively. Of the 333 patients with high cortactin expression, 204, 58, and 71 had luminal, HER2, and triple-negative breast cancer (TNBC), respectively. In the univariate and multivariate analyses of patients with TNBC, cortactin expression was found to be a significant prognostic factor for overall survival (OS). However, in all patients with non-TNBC, cortactin expression had no significant association with prognosis or overall survival. Survival curves revealed that among patients with TNBC, the high-cortactin group had a better prognosis in disease-free survival and OS. Conclusions: Cortactin expression may be a good biomarker for predicting the prognosis of patients with TNBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Core needle biopsy (CNB) and fine needle aspiration (FNA) are the most commonly used non-surgical tissue sampling methods for breast cancer diagnosis. CNB has higher diagnostic accuracy and enables molecular subtype determination for neoadjuvant chemotherapy, and is more widely used than FNA. However, FNA is less invasive and provides faster results, and is still performed by many clinicians. This study was conducted to investigate the prognosis and application criteria of the two methods in real clinical practice. We found that patients who were diagnosed with breast cancer using FNA had significantly worse survival rates than those diagnosed using CNB. In the subgroup analysis, FNA showed worse survival rates in cases of highly suspicious lesions, nonpalpable tumors, or centrally located tumors. Our study may help in choosing the appropriate tissue sampling method for suspected breast cancer cases. (1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA (n = 8027) and CNB (n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors. [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]

Simple Summary: Breast reirradiation could represent a valuable option for local recurrence of breast cancer in previously irradiated sites. We aimed to report on the efficacy and tolerability of this treatment in our institution. The results of this series combined with those available in the literature indicate that breast/chest wall reirradiation is feasible with good oncological results and low toxicity rates. Background: The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue. The aim of this work was to report our experience with breast reirradiation for locoregionally recurrent breast cancer. Methods: All patients who underwent breast or chest wall in-field reirradiation at the Institut Curie, Paris, France, between 2003 and 2019, were identified. Efficacy outcomes and physician-reported toxicities were retrospectively assessed. Results: A total of 21,372 patients underwent breast irradiation in our institution. Of these, 28 received a second course of radiotherapy to the homolateral breast/chest wall. A total of 18 (64%) patients were treated with a curative intent, and 10 (36%) were treated for palliative purposes. Only one acute and one late grade 3 adverse events were reported. One patient with major cardiovascular risk factors died of myocardial infarction 13 months after left breast reirradiation. The 2-year LRFS, OS, DSS, PFS and MFS were 59%, 79%, 82%, 46% and 75%, respectively, in the whole cohort. The 2-year LRFS (72% vs. 31%, p = 0.02), OS (94% vs. 50%, p < 0.01), DSS (94% vs. 56%, p < 0.01) and PFS (61% vs. 20%, p = 0.02) differed significantly between patients treated with curative or palliative intent but not the MFS (78% vs. 69%, p = 0.77). Among the patients, eight (29%) remained relapse-free 5 years after reirradiation. Conclusion: Breast/chest wall reirradiation appears to be feasible with good disease control, especially in patients treated with a curative intent, and presents acceptable toxicity rates. [ABSTRACT FROM AUTHOR]