Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2's protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values < 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p < 0.0001), and a high proliferation index (p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.

Post-surgery statin use contributes to favorable outcomes in patients with early breast cancer.

BACKGROUND: Statins are a group of lipid-lowering drugs with pleiotropic effects that include, but are not limited to the inhibition of cholesterol synthesis resulting in a wide range of anti-inflammatory, anti-tumor, immunomodulatory, and anti-thrombotic properties. This study aimed to determine the impact of the prior to- or after- breast surgery usage of statins on the tumor prognosis in breast cancer (BC) patients. METHODS: A cohort of patients diagnosed with early invasive ductal BC (n=301) at the Hospital Italiano de Buenos Aires, Argentina, with a minimum follow-up period of 10 years after the surgical procedure were included and stratified according to the time of use of statins and type of statin used. Then, local relapse-free survival (RFS), metastasis-free survival (MFS), bone metastasis-free survival (BMFS), visceral metastasis-free (VMFS), mixed metastasis (bone and visceral)-free survival (mix-MFS) and overall survival (OS) were analyzed. RESULTS: Statins usage after breast surgery was related with lesser metastatic occurrence (p=0.017), lower number of metastatic foci (p=0.034) and fewer dead events (p=0.041), as well as longer MFS (p=0.013) and OS (p=0.027). When stratified by the nature of statins (hydrophilic or lipophilic), only the relatively hydrophilic statin rosuvastatin (ROSU) had an impact on the increase of MFS and OS (p=0.018 and p=0.030, respectively). CONCLUSION: Post-surgery statins usage was associated with increased MFS and OS, with increased benefits of ROSU over simvastatin (SIM) or atorvastatin (ATOR). These results set the rationale for additional studies addressing the use of statins, and particularly, rosuvastatin, to improve the outcome of BC patients.

STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.

PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data. METHODS: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis. RESULTS: Increased STK3 expression in breast cancer was significantly associated with higher pathological cancer stages, and a different expression level was observed in the intrinsic subtypes of breast cancer. Kaplan-Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p < 0.05). The multivariate analysis unveiled a strong correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34-0.94, p = 0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42-0.92, p = 0.017) for all deceased patients. Additionally, in the METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64-0.91, p = 0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical significance (FDR < 0.25 and p < 0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3. CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.

Effects of hormone receptor status on patient clinic and survival in HER2 positive breast cancer.

BACKGROUND: In the current study, the effect of hormone receptor (HR) status on clinical and survival in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer was investigated. METHODS: Two hundred ninety-one patients with HER2- positive were examined in two categories as HR-positive and HR-negative. RESULTS: Of these, 197 (68%) were HR-positive and 94 (32%) were HR-negative with a mean follow-up period of 68 ± 2.7 months. The groups were found to be similar in terms of age, menopausal status, comorbidity, pathologic type, stage, T stage, N stage, lymphovascular invasion, presence and percentage of intraductal component, multicentricity/focality and extracapsular invasion. Family history (P = 0.038), stage 2 tumor rate (P < 0.001), and perineural invasion (P = 0.005) were significantly higher in the HR-positive group. In the HR-negative group, mean Ki-67 value (P = 0.014), stage 3 tumor rate (P < 0.001), tumor necrosis (P = 0.004) and strong (3+) HER2 staining on immunohistochemical staining (P = 0.003) were higher. The incidence of relapse and metastasis, and the localization of metastasis were similar in both patient groups. The rate of locoregional relapse during the first 2 years was higher in the HR-negative patients than in the HR-positive patients (P = 0.023). Overall survival (OS) and disease-free survival (DFS) did not differ between the groups in univariate analysis. However, HR status was determined as an independent prognostic factor (HR: 2.11, 95% CI: 1.17-3.79; P = 0.012) for OS was not found to be significant for DFS in multivariate analysis. CONCLUSION: Both clinicopathologic features and OS outcomes of HR-negative patients were worse than those of HR-positive patients.

Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.

BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast. MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software. RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV. CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.

Deep learning of quantitative ultrasound multi-parametric images at pre-treatment to predict breast cancer response to chemotherapy.

In this study, a novel deep learning-based methodology was investigated to predict breast cancer response to neo-adjuvant chemotherapy (NAC) using the quantitative ultrasound (QUS) multi-parametric imaging at pre-treatment. QUS multi-parametric images of breast tumors were generated using the data acquired from 181 patients diagnosed with locally advanced breast cancer and planned for NAC followed by surgery. The ground truth response to NAC was identified for each patient after the surgery using the standard clinical and pathological criteria. Two deep convolutional neural network (DCNN) architectures including the residual network and residual attention network (RAN) were explored for extracting optimal feature maps from the parametric images, with a fully connected network for response prediction. In different experiments, the features maps were derived from the tumor core only, as well as the core and its margin. Evaluation results on an independent test set demonstrate that the developed model with the RAN architecture to extract feature maps from the expanded parametric images of the tumor core and margin had the best performance in response prediction with an accuracy of 88% and an area under the receiver operating characteristic curve of 0.86. Ten-year survival analyses indicate statistically significant differences between the survival of the responders and non-responders identified based on the model prediction at pre-treatment and the standard criteria at post-treatment. The results of this study demonstrate the promising capability of DCNNs with attention mechanisms in predicting breast cancer response to NAC prior to the start of treatment using QUS multi-parametric images.

Analysis of breast cancer survival in a northeastern Brazilian state based on prognostic factors: A retrospective cohort study.

Breast cancer is a major health problem worldwide. Analysis of breast cancer epidemiology in emerging countries enables assessment of prognostic factors, cancer care quality, and the equity of resource distribution. We aimed to estimate the overall (OS) and cancer-specific survival (SS) of breast cancer patients in the northeastern Brazilian state of Sergipe to identify independent prognostic factors. We analyzed a cohort for the factors age at diagnosis, place of residence, time to treatment, staging, and molecular classification, using the Kaplan-Meier method, log-rank test, Pearson's chi-squared test and Cox regression model. The outcome was the vital status at the end of the study. Our analysis showed an OS probability of 0.72 and an SS probability of 0.75. In multivariate analysis, time to treatment within 60 days, stage IV, and triple-negative classification remained independent prognostic factors for both OS [unadjusted hazard ratio (HRp) 1.50 (1.21; 1.86), HRp 16.56 (8.35; 32.85), and HRp 2.73 (1.73; 4.29), respectively] and SS [HRp 1.43 (1.13; 1.81), HRp 20.53 (9.45; 44.56), and HRp 3.14 (1.88; 5.26), respectively]. Better survival was demonstrated for the following patients: those receiving their first treatment after 60 days, with an OS of 52.5 months (51.2; 53.8) and SS of 53.5 months (52.3; 54.7); stage I patients, with an OS of 58.8 months (57.7; 60.0) and SS of 59.2 months (58.1; 60.3); patients without nodal metastasis, with an OS of 54.2 months (53.0; 55.4) and SS of 55.6 months (54.5; 56.7); and patients with luminal A classification, with an OS of 56.8 months (55.0; 58.5) and SS of 57.8 months (56.2; 59.4). This study identified independent prognostic factors and that OS and SS were lower for patients from Sergipe than for patients in high-income areas. Therefore, determining the profiles of breast cancer patients in this population will inform specific cancer care.

Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.

BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041). CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.

Investigating the effectiveness of adjuvant therapy for patients with hormone receptor-positive ductal carcinoma in situ.

BACKGROUND: This study compared the recurrence risk of single versus dual adjuvant radiotherapy (RT) and hormonal therapy (HT) following breast-conserving surgery (BCS) in patients with hormone receptor-positive ductal carcinoma in situ (DCIS). METHODS: This retrospective cohort study used the Taiwan Cancer Registry database linking to the Taiwan National Health Insurance data from 2011 to 2016. We compared the recurrence risk between BCS-based regimens in Cox regressions and presented as adjusted hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: The 1,836 study cohort with a low-to-intermediate risk of recurrence was grouped into BCS alone (6.1%), BCS+RT (6.2%), BCS+HT (23.4%) and BCS+HT+RT (64.3%) according to the initial treatments. During the follow-up (median: 3.3 years), the highest 5-year recurrence-free survival rate was in BCS+RT (94.1%) group and followed by BCS+HT+RT (92.8%), BCS+HT (87.4%) and BCS alone (84.9%). Of the single adjuvant therapies, RT was more effective than HT. Both BCS+HT (HR: 1.52, 95%CI: 0.99-2.35) and BCS+RT (HR: 1.10, 95%CI: 0.50-2.41) did not significantly increase recurrence risk comparing against the BCS+HT+RT group. CONCLUSION: Single adjuvant demonstrated a similar subsequent recurrence risk with dual adjuvant. This study supports the proposition to de-escalate adjuvant treatments in patients with low-to-intermediate risk of DCIS recurrence.

Features from MRI texture analysis associated with survival outcomes in triple-negative breast cancer patients.

PURPOSE: The purpose of the study is to evaluate the associations between intratumoral or peritumoral textural features derived from pretreatment magnetic resonance imaging (MRI) and recurrence-free survival (RFS) in triple-negative breast cancer (TNBC) patients. METHODS: Forty-three patients with TNBC who underwent preoperative MRI between February 2008 and March 2014 were included. We performed two-dimensional texture analysis on the intratumoral or peritumoral region of interest (ROI) on axial of T2-weighted image (T2WI), dynamic contrast-enhanced (DCE)-MRI and DCE-MRI subtraction images. We also analyzed histopathological data. Cox proportional hazards models were used to investigate associations with survival outcomes. RESULTS: Twelve of the 43 patients (27.9%) had recurrence disease, at a median of 32.5 months follow-up (1.4-61.5 months). In univariate analysis, nine texture features in T2WI and DCE-MRI subtraction images were significantly associated with RFS. In multivariate analysis, intratumoral difference entropy in DCE-MRI subtraction images in the initial phase (hazard ratio 11.71; 95% confidence interval (CI) [1.41, 97.00]; p value 0.023) and, peritumoral difference variance in DCE-MRI subtraction images in the delayed phase (hazard ratio 9.60; 95% CI [1.98, 46.51]; p value 0.005), were both independently associated with RFS. Moreover, multivariate analysis revealed the presence of lymphovascular invasion as independently associated with RFS (hazard ratio 8.13; 95% CI [2.16, 30.30]; p value 0.002). CONCLUSIONS: At pretreatment MRI, an intratumoral and peritumoral quantitative approach using texture analysis has the potential to serve as a prognostic marker in patients with TNBC.

Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.

OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis. METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry. RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2  = 18784, p < 0.001; χ2  = 47.1, p < 0.001; χ2  = 20, p < 0.001). CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.

Comparative analysis of clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast and invasive ductal carcinoma: results from SEER database.

PURPOSE: To investigate the difference of clinicopathologic characteristics and prognosis between invasive papillary carcinoma (IPC) and invasive ductal carcinoma (IDC) in breast cancer patients, and to further confirm the influence of molecular subtype on prognosis of IPC. METHODS: A total of 158,132 eligible patients from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, of which 348 patients were IPC and 157,784 patients were IDC. We assessed the clinicopathologic characteristics, molecular subtypes and prognostic value of IPC and compared them with those of IDC. RESULTS: IPC was more frequently presented with older age at diagnosis, less proportion of married and white race, lower grade, smaller tumor size, higher rates of negative nodal status, more AJCC stage I disease and HR+/Her2- breast cancer, and was less likely to be treated with mastectomy, chemotherapy, and radiation therapy than IDC (p<0.05). IPC had a better 5-year breast cancer-specific survival (BCSS) and overall survival (OS) rates than IDC. After adjusting confounding and matching the confounding factors, IPC patients were still associated with better BCSS. Regarding patients with specific subtypes, patients with IPC had more HR+/Her2- subtypes. In addition, HR+/Her2--IPC patients had a better BCSS than HR+/Her2--IDC patients, but OS was similar between the two groups. However, BCSS and OS did not differ in the two groups after matching the confounding factors. Subgroup analysis indicated that molecular subtype may be the main confounding factor in IPC prognosis. CONCLUSIONS: IPC showed more favorable behavior than IDC, but prognosis was not as favorable as people once thought. The determination of the appropriate therapeutic regimen for IPC still needs to be made according to risk factors such as histological grade, pathological stage and molecular subtype.

Clinicopathological Characteristics and Prognosis of Squamous Cell Carcinoma of the Breast: A Population-Based Analysis.

BACKGROUND: To better understand the clinicopathological features and prognostic profiles of squamous cell carcinoma (SCC) of the breast. METHODS: Information on breast cancer was obtained from the Surveillance, Epidemiology, and End Results database (2004-2016). Comparative analyses were carried out to investigate the heterogeneity in the clinicopathological characteristics and survival outcomes between SCC and invasive ductal carcinoma (IDC), while propensity score matching was conducted to analyze the variations among baseline characteristics. Prognostic factors for SCC of the breast were successively identified using Cox regression analysis. RESULTS: A total of 382 SCC patients and 561477 IDC patients were identified in this study. Comparatively, the SCC cohort exhibited a higher proportion of male individuals, poor differentiation, an advanced TNM stage, an increasing percentage of triple-negative (TN) subtype, an increasing rate of organ involvement, and less access to therapeutics. The aggressive profile was consistent in the TN subgroup, with a significantly higher proportion in SCC than in IDC (25.7% vs 6.8%). Prognosis of SCC was profoundly poorer than that of IDC (mOS, 78.6 months and 121.6 months, P < .0001; mBCSS 91.9 months vs 135.6 months, P < .0001), of which the inferior tendency remained stable among disease stage and therapeutic options, while no difference was detected in the 2 subgroups with the TN subtype. The 2-year survival rate was 66.9% and the 5-year survival rate was 51.4%, with the risk factors being older age, bilateral disease, advanced TNM stage, bone and visceral involvement, surgical intervention, radiation treatment, and chemotherapy. CONCLUSIONS: This study systematically analyzed the heterogeneous characteristics of SCC of the breast in comparison with IDC. Squamous cell breast cancer presented with increasing aggressive behavior and inferior prognosis. Prospective studies should focus on this subgroup and introduce individualized therapeutic protocols in clinical practice.

The Real-world Outcomes of Patients With Advanced Invasive Lobular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma: A Review at a Single Institution.

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity. PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively. RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow. CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.

Predicting the immune landscape of invasive breast carcinoma based on the novel signature of immune-related lncRNA.

BACKGROUND: The composition of the population of immune-related long non-coding ribonucleic acid (irlncRNA) generates a signature, irrespective of expression level, with potential value in predicting the survival status of patients with invasive breast carcinoma. METHODS: The current study uses univariate analysis to identify differentially expressed irlncRNA (DEirlncRNA) pairs from RNA-Seq data from The Cancer Genome Atlas (TCGA). 36 pairs of DEirlncRNA pairs were identified. Using various algorithms to construct a model, we have compared the area under the curve and calculated the 5-year curve of Akaike information criterion (AIC) values, which allows determination of the threshold indicating the maximum value for differentiation. Through cut-off point to establish the optimal model for distinguishing high-risk or low-risk groups among breast cancer patients. We assigned individual patients with invasive breast cancer to either high risk or low risk groups depending on the cut-off point, re-evaluated the tumor immune cell infiltration, the effectiveness of chemotherapy, immunosuppressive biomarkers, and immunotherapy. RESULTS: After re-assessing patients according to the threshold, we demonstrated an effective means of distinguish the severity of the disease, and identified patients with different clinicopathological characteristics, specific tumor immune infiltration states, high sensitivity to chemotherapy,wellpredicted response to immunotherapy and thus a more favorable survival outcome. CONCLUSIONS: The current study presents novel findings regarding the use of irlncRNA without the need to predict precise expression levels in the prognosis of breast cancer patients and to indicate their suitability for anti-tumor immunotherapy.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer.

BACKGROUND: To develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer. METHODS: Thirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group. RESULTS: Following independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination. CONCLUSIONS: The nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2).

BACKGROUND: The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed. PATIENTS AND METHODS: GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m2, nab-paclitaxel (nP) 330 mg/m2 and cyclophosphamide (C) 2000 mg/m2 (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD). RESULTS: The duration of median follow-up was 45.8 (range 0.0-88.3) months. Trial objectives included invasive disease-free survival (iDFS) as the primary end-point. A total of 593 patients received the treatment as neoadjuvant chemotherapy. At the time of futility interim analysis, 414 events for iDFS were reported. Overall, there was no difference in iDFS between iddEnPC and dtEC-dtD with 4-year iDFS rates of 84.3% (95% confidence interval (CI) 82.0-86.4%). Among all predefined subgroups, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-), lobular cancer and ≤50 years subgroups predicted for better iDFS in the dtEC-dtD arm. Overall, 88.1% of patients completed all treatment in both arms. Haematological toxicity grade 3/4 and grade 3/4 non-haematological adverse events were significantly higher with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, P = 0.002), especially arthralgia and peripheral sensory neuropathy. Two treatment-related deaths occurred during dtEC-dtD, corresponding to a low mortality rate of 0.07%. CONCLUSIONS: iDFS is equal in both regimens, but tailoring dose-dense chemotherapy improved outcomes in HR+/HER2-, lobular cancer and patients ≤50 years.

Neuroglobin: A New Possible Marker of Estrogen-Responsive Breast Cancer.

The expression of the α-subtype of Estrogen Receptor (ERα) characterizes most breast cancers (more than 75%), for which endocrine therapy is the mainstay for their treatment. However, a high percentage of ERα+ breast cancers are de novo or acquired resistance to endocrine therapy, and the definition of new targets for improving therapeutic interventions and the prediction of treatment response is demanding. Our previous data identified the ERα/AKT/neuroglobin (NGB) pathway as a common pro-survival process activated in different ERα breast cancer cell lines. However, no in vivo association between the globin and the malignity of breast cancer has yet been done. Here, we evaluated the levels and localization of NGB in ERα+ breast ductal carcinoma tissue of different grades derived from pre-and post-menopausal patients. The results indicate a strong association between NGB accumulation, ERα, AKT activation, and the G3 grade, while no association with the menopausal state has been evidenced. Analyses of the data set (e.g., GOBO) strengthen the idea that NGB accumulation could be linked to tumor cell aggressiveness (high grade) and resistance to treatment. These data support the view that NGB accumulation, mainly related to ER expression and tumor grade, represents a compensatory process, which allows cancer cells to survive in an unfavorable environment.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation

Purpose The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. Material and methods Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10–12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. Results The median age was 64.5 years (40–90). The median follow-up was 62 months (4–86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6–52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3–4 chronic toxicity was observed. Grade 1–2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. Conclusions IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment (AU)