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Objective To evaluate the safety of immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flaps in the patients after neoadjuvant treatment. Methods From January 2019 to February 2021, the data of patients with breast cancer undergoing total mastectomy and immediate breast reconstruction using DIEP flap in Comprehensive Breast Health Center, Department of General Surgery, Ruijin Hospital were collected. Comparison of clinicopathological features was done between neoadjuvant treatment group and control group. Univariate analysis was used to compare the rate of surgical complications between two groups. Results A total of 110 patients were enrolled with 23 cases (20.9%) in neoadjuvant treatment group and 87 cases (79.1%) in control group. None of carcinoma in situ (0 vs. 19.5%, P=0.003) and higher pTNM stage (P

Objective: To analyze the diagnosis, treatment and prognosis of breast cancer patients in Ruijin Hospital for further clinical management and study. Methods Non-metastatic breast cancer patients with surgical treatment in our hospital were included from January 2009 to December 2018. Clinicopathological features of enrolled patients and chan-ging trend of different surgery including breast conserving surgery and sentinel lymph node biopsy (SLNB) in the period of this study were analyzed. Kaplan-Meier curve analysis was used to compare 5-year and 10-year disease free survival (DFS) and overall survival(OS) of patients with different treatments. Results This study had 8 210 patients. There were 959 (11.7%) patients with in situ disease and 5 379(71.3%) patients with negative lymph node in 7 549 patients without neoadjuvant therapy. There were 949(12.6%) cases and 2964 (39.3%) cases with breast cancer at stage 0 and stage I, respectively. A total of 2377(29.0%) patients underwent breast conserving surgery with increase from 16.5% in 2009 to 34.8% in 2013. The patients with SLNB were 4149 cases (52.5%) from 0.6% in 2009 to 69.3% in 2018. All patients from 2009 to 2018 achieved complete follow-up with a median follow-up of 46 months: 5-year and 10-year DFS were 87.6% and 80.5%; 5-year and 10-year OS were 94.2% and 90.7%, respectively. There were 3800 patients with surgery followed from year 2009 to 2014 with a median-follow-up of 79 months: 5-year DFS rate and OS rate were 86.9% and 93.1%; 10-year DFS rate and OS rate were 79.1% and 88.4%, respectively. Conclusions Both rates of breast conserving surgery and SLNB in Ruijin Hospital increased in last 10 years. Patients had more than 93% of 5-year OS with modern treatment modality of breast cancer, which could indicate clinical management and research in future.

Simple Summary: Anthracycline and taxane-based chemotherapy are the cornerstone of adjuvant therapy for early breast cancer. In recent years, several trials explored the efficacy of the anthracycline-free regimens, especially for HER2-negative breast cancer patients, which turned out to be a feasible alternative. However, there is no comparison between epirubicin and cyclophosphamide versus docetaxel and cyclophosphamide about their safety and efficacy to date. ELEGANT is the first phase III randomized trial comparing the safety and efficacy of EC versus TC, and it reports comprehensive safety profiles of both regimens with a primary endpoint of grade 3 to 4 neutropenia rate. Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group. [ABSTRACT FROM AUTHOR]

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]

Breast cancer (BC) is one of the most common malignant tumors among women worldwide and can be treated using various methods; however, side effects of these treatments cannot be ignored. Increasing evidence indicates that compound kushen injection (CKI) can be used to treat BC. However, traditional Chinese medicine (TCM) is characterized by "multi-components" and "multi-targets", which make it challenging to clarify the potential therapeutic mechanisms of CKI on BC. Herein, we designed a novel system pharmacology strategy using differentially expressed gene analysis, pharmacokinetics synthesis screening, target identification, network analysis, and docking validation to construct the synergy contribution degree (SCD) and therapeutic response index (TRI) model to capture the critical components responding to synergistic mechanisms of CKI in BC. Through our designed mathematical models, we defined 24 components as a high contribution group of synergistic components (HCGSC) from 113 potentially active components of CKI based on ADME parameters. Pathway enrichment analysis of HCGSC targets indicated that Rhizoma Heterosmilacis and Radix Sophorae Flavescentis could synergistically target the PI3K-Akt signaling pathway and the cAMP signaling pathway to treat BC. Additionally, TRI analysis showed that the average affinity of HCGSC and targets involved in the key pathways reached -6.47 kcal/mmol, while in vitro experiments proved that two of the three high TRI-scored components in the HCGSC showed significant inhibitory effects on breast cancer cell proliferation and migration. These results demonstrate the accuracy and reliability of the proposed strategy. [ABSTRACT FROM AUTHOR]

Background: The 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages. Methods: A total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules. Results: In patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients. Conclusions: RS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks. [ABSTRACT FROM AUTHOR]

Synthetic digital mammography (SDM), a 2D image generated from digital breast tomosynthesis (DBT), is used as a potential substitute for full-field digital mammography (FFDM) in clinic to reduce the radiation dose for breast cancer screening. Previous studies exploited projection geometry and fused projection data and DBT volume, with different post-processing techniques applied on re-projection data which may generate different image appearance compared to FFDM. To alleviate this issue, one possible solution to generate an SDM image is using a learning-based method to model the transformation from the DBT volume to the FFDM image using current DBT/FFDM combo images. In this study, we proposed to use a deep convolutional neural network (DCNN) to learn the transformation to generate SDM using current DBT/FFDM combo images. Gradient guided conditional generative adversarial networks (GGGAN) objective function was designed to preserve subtle MCs and the perceptual loss was exploited to improve the performance of the proposed DCNN on perceptual quality. We used various image quality criteria for evaluation, including preserving masses and MCs which are important in mammogram. Experiment results demonstrated progressive performance improvement of network using different objective functions in terms of those image quality criteria. The methodology we exploited in the SDM generation task to analyze and progressively improve image quality by designing objective functions may be helpful to other image generation tasks. [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: The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS.Methods: We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models.Results: A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772-0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781-0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685-0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804-0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. CONCLUSIONS: We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing. [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: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear. Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment. Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29–0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27–1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18–0.89), were premenopausal (HR, 0.34; 95% CI, 0.12–0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17–0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25–0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26–0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence. Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors. [ABSTRACT FROM AUTHOR]

Recurrence score (RS) could be used to predict clinical outcomes and chemotherapy efficacy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. However, the clinical features and management of patients with an RS of 26–30 are not completely understood. In the present study, 783 patients with HR+/HER2−, lymph node-negative early breast cancer and RS ≥18 were included and categorized into RS=18−25 (47.8%), 26–30 (25.5%) or ≥31 (26.7%) groups. Clinicopathological characteristics, adjuvant chemotherapy usage and disease outcomes were compared. Alterations in the adjuvant chemotherapy recommendation after 21-gene RS testing were also analyzed. The results indicated that patients with RS=26−30 had higher progesterone receptor (PR) expression [odds ratio (OR)=2.84; P<0.001] and lower Ki-67 index (OR, 1.88; P=0.032) compared with patients with RS ≥31. Multivariate analysis demonstrated that age ≤50 years (OR, 5.75; P=0.001) and luminal-B subtype (OR, 7.75; P<0.001) were factors that were independently associated with chemotherapy usage in the RS=26−30 group. Among 104 patients who were not recommended chemotherapy before 21-gene RS testing, the treatment decision for 52 patients was changed to recommend chemotherapy once an RS of 26–30 was identified. The patient adherence rate to the treatment recommendation was 95.0% (190/200). After a median follow-up of 21.5 months, 6 patients displayed disease recurrence in the RS=26−30 group, and there was no significant difference between patients receiving chemotherapy and patients not receiving chemotherapy. In conclusion, patients with RS=26−30 had tumors with higher PR expression and lower Ki-67 index compared with those of patients with RS ≥31. Age, luminal subtype and RS testing influenced chemotherapy usage in patients with RS=26−30; however, no significant benefit from adjuvant chemotherapy was observed in a short term of 2 years. [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]

Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ≤1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging. Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18–30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated. Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%. Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients. [ABSTRACT FROM AUTHOR]

Purpose: Dysmetabolism and high circulating insulin-like growth factor 1 (IGF-1) would increase breast cancer risk, but its association with survival in HER2+ breast cancer patients has not been well-studied. Herein, we aim to evaluate the prognostic value of IGF-1 and metabolic abnormalities in HER2+ population. Patients and Methods: HER2+ breast cancer patients treated in Ruijin Hospital between November 2012 and June 2017 were retrospectively analyzed. Median value of circulating IGF-1 was adopted to classify low or high IGF-1 group. Metabolic syndrome (MetS) was defined using AHA/NHLBI criteria. Overweight was defined by body mass index (BMI) ≥ 24.0 kg/m2 in Chinese population. Results: Overall, 679 patients were included and 209 had synchronous MetS. High IGF-1 level was more common in pre/peri-menopausal women (P < 0.001) and high IGFBP-3 patients (P < 0.001). After a median follow-up of 36 months, 52 patients had disease recurrences. IGF-1 level was not associated with recurrence-free survival (RFS, P = 0.620) in the whole population. However, exploratory subgroup analysis found that BMI and IGF-1 interacted in predicting RFS (P = 0.009). For non-overweight patients, high IGF-1 showed a superior 4-years RFS (91.1 vs. 85.0%; HR 0.53, 95% CI 0.27–1.00, P = 0.049) compared with patients with low IGF-1 level. In contrast, for overweight patients, high IGF-1 was associated with an impaired 4-years RFS (88.3 vs. 95.7%, HR 3.20, 95% CI 1.00–10.21, P = 0.038). Furthermore, high IGF-1 level was independently associated with better OS in the whole (HR 0.26, 95% CI 0.08–0.82, P = 0.044) as well as non-overweight population (HR 0.15, 95% CI 0.03–0.68, P = 0.005). Conclusions: IGF-1 level was not associated with RFS in HER2+ breast cancer patients. However, IGF-1 and BMI had significant interaction in disease outcome prediction in HER2+ patients. High IGF-1 was protective in non-overweight patients, but risk factor for those overweight, which deserves further evaluation. [ABSTRACT FROM AUTHOR]

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR+/HER2− patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58–152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90–6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42–145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39–1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR+/HER2− patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

Danggui Buxue Decoction (DBD), a classical formula of traditional Chinese medicine (TCM), has an impact on promoting hematopoiesis. The aim of our study was to determine whether DBD can prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. We conducted a phase II randomized prospective controlled clinical study. From December 2013 to February 2015, 106 patients were enrolled and randomly assigned (1:1) to the TCM group and control group. The primary end point was incidence of grade 3-4 neutropenia. The secondary end points included incidence of grade 3-4 neutropenia in each cycle, incidence of anemia, and incidence of thrombopenia during 4 cycles. Seventeen patients withdrew from this study, and 89 patients were included in the final analysis. Incidences of grade 3-4 neutropenia during 4 cycles were 57.1% in the TCM group and 59.6% in the control group, and there was no significant difference (P = .816). Similarly, no significant differences were observed between the 2 groups for incidence of grade 3-4 neutropenia in each cycle. While incidences of anemia were 54.8% and 66.6% for the TCM group and control group, respectively (P = .280), incidences of thrombopenia were 11.9% for the TCM group and 4.3% for the control group (P = .248). No significant differences were observed for the incidence of other nonhematological toxicities between the 2 groups. DBD failed to prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. Further studies are warranted to validate the efficacy of DBD in selected patients. [ABSTRACT FROM AUTHOR]

Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR. The optimal cutoff value was determined as 1.93 for NLR and the median follow-up time was 55.0 months. On univariate analysis, patients with high NLR (>1.93) had worse 5-year disease-free survival (DFS) compared to those with low NLR (77.9 vs 88.0 %, p = 0.002). Regarding overall survival, there was no significant difference between patients with high NLR and low NLR, with 5-year overall survival of 90.8 and 91.7 % ( p = 0.707). In triple-negative breast cancer, patients with high NLR was associated with worse 5-year DFS compared with patients with low NLR (63.4 vs 84.9 %, p = 0.040). Mutivariate analysis revealed that NLR was an independent prognostic factor for DFS in breast cancer (HR = 1.867, 95 % confidence interval; (95%CI) = 1.155-3.017, p = 0.011). Preoperative NLR is an independent predictor of DFS in breast cancer patients, especially in triple-negative subtype. Further studies are required to validate the prognostic value of NLR before clinical application. [ABSTRACT FROM AUTHOR]

Background: The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure. Material and Methods: In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines. Results: Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line. Conclusions: Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer. [ABSTRACT FROM AUTHOR]

The 21-gene recurrence score (RS) assay is prognostic and predictive for hormone receptor (HR)+/HER2-/node- breast cancer (BC) patients. However, its clinical value in node + patients hasn't been elucidated. HR+/HER2-/pN1 patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital from January 2014 to December 2018, with available RS results were retrospectively included. Clinico-pathological characteristics were compared. Adjuvant chemotherapy recommendations pre-/post- RS assay and actual usage were analyzed. A total of 303 patients were included, with 59, 178, 66 RS < 18, 18–30 and ≥ 31. Age (P < 0.001), comorbidity (P = 0.013), and RS category (P < 0.001) were independently associated with chemotherapy recommendation. Compared with low RS patients, those with intermediate (OR 6.58, 95% CI 2.37–18.31, P < 0.001) or high (OR 54.14, 95% CI 3.77–776.54, P = 0.003) RS were more likely to be recommended with chemotherapy. RS independently influence chemotherapy decision in postmenopausal population as well. Chemotherapy recommendation changed for 9.57% patients after RS assay. Patient adherence rate to chemotherapy recommendation was 94.72% (287/303). The 21-gene RS independently influenced chemotherapy recommendation in pN1 BC patients, which could provide additional information to guide chemotherapy decision with relatively good treatment adherence rate. [ABSTRACT FROM AUTHOR]

Background Increasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours. Patients and methods Patients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level. Results Among 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours ( P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups ( P = 0.43). Conclusion HER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation. [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]

Multifaceted features decoded from mammographic images may describe various perspectives of the breast mass heterogeneity, in this study, we aimed to explore a methodology to effectively integrate multifaceted mass representations extracted from the digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) to enhance breast cancer discrimination. A novel multi-criterion decision making-based multi-channel fusion (MDMF) framework was proposed to fuse different breast mass representations processed in multi-channels built on the deep convolutional neural network (DCNN) and the multilayer perceptron (MLP) at the decision level. A hierarchical framework (HFMM) was also developed for multi-modality images and multi-channel fusion to integrate multimodality information from DBT and FFDM. We retrospectively collected 441 patients with both DBT and FFDM, and the regions of interest (ROIs) covering the malignant, benign, and normal tissues were extracted for validation. The MDMF achieved the area under the receiver operating characteristic curve (AUC) of 93.14%, 91.30%, 97.35% (FFDM) and 93.79%, 95.16%, 99.31% (DBT) respectively for the malignant, benign and normal mass. While the HFMM further boosted the performance to AUC of malignant 94.14%, benign 95.42% and normal mass 99.56% The matthews correlation coefficient (MCC) were 73.15% and 81.02% for FFDM and DBT accomplished by MDMF, and enhanced to 81.72% when integrating the multimodality information from DBT and FFDM via the proposed HFMM. The experimental results suggested that the proposed HFMM achieved superior discriminative performance when compared with the benchmark classification algorithms and fusion architectures, rendering it a practical tool for breast mass discrimination in breast cancer screening. • A decision making-based multi-channel fusion (MDMF) framework is proposed. • Proposed framework is based on deep convolutional network and multilayer perception. • Hierarchical fusion framework (HFMM) is designed to integrate multimodality DBT and FFDM images. • The proposed methods will aid in computer aided breast cancer screening. [ABSTRACT FROM AUTHOR]