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Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab. Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab. We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis. Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10, P=0.003), pN2-3(HR=2.81, P

Purpose: This study aimed to evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes. Methods: MMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed using Kappa test and categorized into the homogeneous group (Homo group) and the heterogeneous group (Hetero group). Chi-square tests were performed to compare the clinical features and treatment options between the groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan–Meier curves and compared between two groups. Results: A total of 387 patients were included, and 93 (24.0%) were classified into the Hetero group. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, p = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, p = 0.196) and chemotherapy (69.9% vs. 69.8%, p = 0.987) usage between the two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (p = 0.041; adjusted HR , 2.95; 95% CI, 1.04–8.37). The estimated 3-year OS rates for the groups were 95.8% and 99.5%, respectively (p = 0.059; adjusted HR , 5.36; 95% CI, 0.97–29.69). Conclusion: Heterogeneity of ER, PR, HER2, or Ki67 was present in 24.0% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of obesity on clinicopathological characteristics of breast cancer; to explore the effect of obesity on the prognosis and performance of endocrine therapy in breast cancer patients. Methods: Patients with luminal/HER2-negative early breast cancer were included and categorized into the non-obese (BMI<28kg/m2) and obese (BMI≥28kg/m2) groups according to body mass index (BMI). Clinicopathological characteristics and treatment modalities were compared between groups. Interaction of adjuvant endocrine therapy with obesity was analyzed. Results: A total of 2,875 patients were included: 2,598 non-obese and 277 obese. A higher rate of patients with comorbidities (OR: 2.83, 95%CI 2.13-3.74, P <0.001) or PR-positive tumor (OR: 1.63, 95%CI 1.03-2.58, P =0.037) were identified in the obese group. Obesity was not associated with disease recurrence (P =0.839) or overall survival (P =0.140) in the whole population. Subgroup analysis did show an association with worse relapse-free survival (RFS, HR 3.48, 95%CI 1.31-9.22, P =0.012) and overall survival (OS, HR 4.67, 95%CI 1.28-16.95, P =0.019) in luminal A breast cancer. These results could not be reproduced in the luminal B subtype with a RFS (HR 0.78, 95%CI 0.41-1.49, P =0.454) or OS (HR 1.17, 95%CI 0.50-2.74, P =0.727). Furthermore, obesity did not impact endocrine therapy effectiveness in Tamoxifen or the aromatase inhibitor group (RFS: interact P =0.381; OS: interact P =0.888). Conclusions: The impact of obesity on prognosis interacted with luminal subtype status in Chinese breast cancer patients which was not related with endocrine treatment modality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the mammographic features, clinicopathological characteristics, treatments, and prognosis of pure and mixed tubular carcinomas of the breast. Materials and methods: Twenty-five tubular carcinomas were pathologically confirmed at our hospital from January 2011 to May 2019. Twenty-one patients underwent preoperative mammography. A retrospective analysis of mammographic features, clinicopathological characteristics, treatment, and outcomes was performed. Results: Altogether, 95% of the pure tubular carcinomas (PTCs) and mixed tubular carcinomas (MTCs) showed the presence of a mass or structural distortions on mammography and the difference was not statistically significant (P =.373). MTCs exhibited a larger tumor size than PTCs (P =.033). Lymph node metastasis was more common (P =.005) in MTCs. Patients in our study showed high estrogen receptor and progesterone receptor positivity rates, but low human epidermal growth factor receptor 2 positivity rate. The overall survival rate was 100% in both PTC and MTC groups and the 5-year disease-free survival rates were 100% and 75%, respectively with no significant difference between the groups (P =.264). Conclusion: Tubular carcinoma of the breast is potentially malignant and has a favorable prognosis. Digital breast tomosynthesis may improve its detection. For patients with PTC, breast-conserving surgery and sentinel lymph node biopsy are recommended based on the low rate of lymph node metastasis and good prognosis. MTC has a relatively high rate of lymph node metastasis and a particular risk of metastasis. Axillary lymph node dissection should be performed for MTC even if the tumor is smaller than 2 cm. [ABSTRACT FROM AUTHOR]

Purpose: A center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients. Patients and methods: Luminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status. Results: Among 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P =0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P =0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P <0.05). Compared to non-overweight patients, obese ones presented significantly higher ER , PR , CEGP1 , Ki67 , CCNB1 and GSTM1 (all P <0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P =0.001). RS was associated with DFS in non-overweight (P =0.046), but not in overweight (P =0.558) or obese (P =0.114) population. Conclusions: RS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments. Patients and Methods: T1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)−; 2) HER2+; and 3) triple negative (TN) (HR−/HER2−). Patients' characteristics and relapse events were reviewed. Kaplan–Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models. Results: In total, 2,168 patients (1,435 HR+/HER2−, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2−, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11–2.84, P = 0.018] had a higher recurrence risk than HR+/HER2− patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68–7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95–5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005). Conclusion: Molecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC. [ABSTRACT FROM AUTHOR]

Background: Enhancer RNA (eRNA) is a non-coding RNA transcribed by enhancers and has a crucial role in controlling gene transcription. However, the potential functions of eRNA in prostate cancer (PCa) are still not fully understood. Methods: Clinical information and expression data of eRNAs and their target genes for PCa were downloaded from TCGA. Each eRNA in PCa samples was divided into high- and low-expression groups. The Kaplan–Meier method was used to identify the eRNAs significantly associated with the overall survival of PCa. Their correlations with age, prostate-specific antigen (PSA), and tumor stage were analyzed using Spearman coefficients. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) analyzes were used to predict the possible biological functions and pathways associated with eRNAs. Results: We identified 12 eRNAs associated with PCa survival, of which PARGP1 was the most clinically significant. It was associated with biochemical recurrence in PCa patients and was also a valuable complement to distinguish between PSA 0–4 ng/ml and 4–10 ng/ml. GO, and KEEG analysis showed that herpes simplex virus-1 infection was the most biologically significant enriched process. Conclusions: PARGP1 is associated with biochemical recurrence in prostate cancer and contributes to assessing the outcome. [ABSTRACT FROM AUTHOR]

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab. • ER+/HER2+ early breast cancer patients treated with trastuzumab-based chemotherapy had superior prognosis. • ER+/HER2+ early breast cancer patients had distinct patterns of relapse or death from those of ER+/HER2-patients. • HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab. [ABSTRACT FROM AUTHOR]

Background: Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Methods: Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). Results: The F2P Score was established by integrating the clinical (age and tumor size) and genomic (ESR1, PGR, BCL2, CD68, GSTM1 , and BAG1) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62–0.81) and BIC was 396.75 (95% CI, 252.37–541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87–4.61) or categorical (HR, 3.68; 95% CI, 1.70–8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. Conclusion: The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown. Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups. Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS. Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC. Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients' clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan–Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC. A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661–6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199–15.436; P < 0.001). TNBC with vertical orientation in ultrasound imaging had higher ALN metastasis burden than those with sonographic parallel features (2.7 ± 1.0 vs 1.5 ± 0.2, P = 0.003). TNBC presenting with vertical orientation in ultrasound imaging was associated with worse disease outcome and a greater number of ALN metastasis. • In TNBC, vertical orientation in US was associated with inferior RFS. • Vertical orientation in US independently predicted worse BCSS in TNBC. • Vertical orientation in US was related with more ALN metastasis in TNBC patients. [ABSTRACT FROM AUTHOR]

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Background: To compare the efficacy of concurrent and sequential administration of radiotherapy and chemotherapy on patients with operable breast cancer after breast.conserving surgery. (BCS).Materials and Methods: We searched MEDLINE (National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier, Amsterdam, Netherlands) databases for eligible studies. Clinical outcomes (such as overall and locoregional recurrence-free survival, toxicity related complications) used as evaluation indexes of efficacy. Odds ratios (ORs) with 95% confidence intervals (CI) of each index was calculated and analyzed with the RevMan Version 5.2 software.Results: Three articles (two trials), which compared the clinical efficacy of concurrent and sequential administration of radiotherapy and chemotherapy for operable breast cancer patients, were eligible in this meta-analysis. There were significant differences between concurrent and sequential treatments in 5-year loco-regional recurrence free survival (OR: 0.39, 95% CI: 0.20-0.75, P = 0.005) and late skin toxicity of telangiectasia (OR: 2.00, 95% CI: 1.39-2.87, P = 0.0002). However, no significant difference was discovered in five-year overall survival (OR: 0.62, 95% CI: 0.35-1.11, P > 0.05), acute skin toxicity (OR: 1.73, 95% CI: 0.98-3.04, P > 0.05) and late skin toxicity of lymphedema (OR: 1.27, 95% CI: 0.88-1.83, P > 0.05).Conclusion: Our study demonstrated that the concurrent administration of chemotherapy (anthracycline-based) and radiotherapy was superior to the sequential administration in locoregional recurrence-free survival for the operable node positive breast cancer patients. However, choose of treatment for operable breast cancer patients must be cautious due to high risk of lymphedema. [ABSTRACT FROM AUTHOR]

Background and Objective: In recent years, an increasing number of clinical prediction models have been developed to serve clinical care. Establishing a data-driven prediction model based on large-scale electronic health record (EHR) data can provide a more empirical basis for clinical decision making. However, research on model generalization and continuous improvement is insufficiently focused, which also hinders the application and evaluation of prediction models in real clinical environments. Therefore, this study proposes a multicenter collaborative prediction model construction framework to build a prediction model with greater generalizability and continuous improvement capabilities while preserving patient data security and privacy.Materials and Methods: Based on a multicenter collaborative research network, such as the Observational Health Data Sciences and Informatics (OHDSI), a multicenter collaborative prediction model construction framework is proposed. Based on the idea of multi-source transfer learning, in each source hospital, a base classifier was trained according to the model research setting. Then, in the target hospital with missing calibration data, a prediction model was established through weighted integration of base classifiers from source hospitals based on the smoothness assumption. Moreover, a passive-aggressive online learning algorithm was used for continuous improvement of the prediction model, which can help to maintain a high predictive performance to provide reliable clinical decision-making abilities. To evaluate the proposed prediction model construction framework, a prototype system for colorectal cancer prognosis prediction was developed. To evaluate the performance of models, 70,906 patients were screened, including 70,090 from 5 US hospital-specific datasets and 816 from a Chinese hospital-specific dataset. The area under the receiver operating characteristic curve (AUC) and the estimated calibration index (ECI) were used to evaluate the discrimination and calibration of models.Results: Regarding the colorectal cancer prognosis prediction in our prototype system, compared with the reference models, our model achieved a better performance in model calibration (ECI = 9.294 [9.146, 9.441]) and a similar ability in model discrimination (AUC = 0.783 [0.780, 0.786]). Furthermore, the online learning process provided in this study can continuously improve the performance of the prediction model when patient data with specified labels arrive (the AUC value increased from 0.709 to 0.715 and the ECI value decreased from 13.013 to 9.634 after 650 patient instances with specified labels from the Chinese hospital arrived), enabling the prediction model to maintain a good predictive performance during clinical application.Conclusions: This study proposes and evaluates a multicenter collaborative prediction model construction framework that can support the construction of prediction models with better generalizability and continuous improvement capabilities without the need to aggregate multicenter patient-level data. [ABSTRACT FROM AUTHOR]

• A novel immune-related prognostic signature was constructed for breast cancer. • The immune-related prognostic signature was an independent predictor for OS. • The nomogram integrating clinical factors and the IRPS was constructed. In the view that immune-related genes play a crucial role in breast cancer progression and long-term patient outcomes, we aimed to identify a novel gene signature based on immune-related genes to improve the prognostic prediction of breast cancer. RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression analyses were conducted to establish the immune-related prognostic signature (IRPS). Then, the IRPS was validated by Kaplan–Meier analyses, time-dependent ROC curve analyses and multivariate Cox regression analyses. External validation was conducted in GSE96058. Nomogram combining IRPS with clinical factors was developed and then validated by time-dependent ROC curve analyses and calibration plots. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression level of immune-related genes in tumor and normal tissues. The IRPS based on 4 immune-related genes (CCL1, VGF, TSLP, FABP9) were constructed. Patients in the low-risk group had significantly better overall survival than those in the high-risk group (p = 0.0011 in the training set, p = 0.0043 in the validation set, p < 0.0001 in the entire set, p < 0.001 in the external validation set). Multivariate analyses indicated that IRPS could independently predict OS in the training set (HR, 0.48; 95% CI, 0.24–0.83; p = 0.009), validation set (HR, 0.55; 95% CI, 0.34–0.90; p = 0.018), entire set (HR, 0.52; 95% CI, 0.36–0.75; p < 0.001) and external validation set (HR: 0.74, 95% CI: 0.59–0.92, p = 0.007). Sequentially, we establish a nomogram by integrating IRPS and clinical factors, which showed satisfactory predictive performance with 3-year, 5-year, 10-year AUC of 0.701, 0.706 and 0.694. Results of qRT-PCR validated that higher expression level of FABP9, CCL1 and VGF and lower expression level of TSLP in tumor samples compared to normal tissues. Collectively, a four-gene based IRPS was developed and validated for patients with breast cancer. As an independent and robust predictor, the IRPS was constructive to risk stratification of breast cancer. [ABSTRACT FROM AUTHOR]