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Background: The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2-) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS., Methods: We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2- BC and eligible 70-GS test. Comparison of 40 parameters including the patients' medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS., Results: Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p < 0.001) and no significant differences in all the imaging parameters of ultrasound and mammogram. The IHC3 risk and the NPI calculated score significantly correlated with both the binary and quartile categorized 70-GS risk classifications (both p < 0.001). The area under curve (AUC) of receiver-operating curve (ROC) of nomogram for binary risk prediction were 0.826 (C-index 0.903, 0.799-1.000) for training and 0.737 (C-index 0.785, 0.700-0.870) for validation dataset respectively. The AUC of ROC of nomogram for quartile risk prediction was 0.870 (C-index 0.854, 0.746-0.962) for training and 0.592 (C-index 0.769, 0.703-0.835) for testing set. The prediction accuracy of the nomogram for quartile categorized risk groups were 55.0% (likelihood ratio tests, p < 0.001) and 53.3% (p = 0.04) for training and validation, which more than double the baseline probability of 25%., Conclusions: To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing., (© 2023. The Author(s).)

Background: Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post-5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction., Methods: Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (<36 months, between 36 and 60 months, and >60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters., Results: In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival <36 months (early recurrence subset), 36-60 months (intermediate recurrence subset) and >60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P < 0 0.001). RS model showed better performance for breast cancer specific survival (BCSS) in late recurrence subsets and worse performance in early and intermediate recurrence subsets than CTS5 (likelihood ratio test P < 0 0.001). For calibration, CTS5 model was superior to RS model for OS, which overestimated the recurrence risk in low-risk subgroup. Both models overestimated the risk for BCSS. In either early/intermediate/late recurrence patient subsets, there was no significant difference in NRI between two models in terms of both BCSS and OS, indicating the two models had comparable prognostic value. The nomogram which combined these two models largely improved the discrimination and calibration power (C-index 0.70-0.72)., Conclusions: Our study proved the CTS5 risk model had comparable prognostic value as RS in HR + breast cancer patients. And the novel nomogram model had better discrimination and calibration than both CTS5 and RS, and future large-scale clinical trials are warranted for further validation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study was conducted to evaluate the prognostic significance of different molecular typing methods and immune status based on RNA sequencing (RNA-seq) in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR + /HER2-) early-stage breast cancer and develop a modified immunohistochemistry (IHC)-based surrogate for intrinsic subtype analysis., Methods: The gene expression profiles of samples from 87 HR + /HER2- early-stage breast cancer patients were evaluated using the RNA-seq of Oncotype Dx recurrence score (RS), PAM50 risk of recurrence (ROR), and immune score. Intrinsic tumor subtypes were determined using both PAM50- and IHC-based detection of estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor, and cytokeratins 14 and 5/6. Prognostic variables were analyzed through Cox regression analysis of disease-free survival (DFS) and distant metastasis-free survival (DMFS)., Results: Survival analysis showed that ROR better predicted recurrence and distant metastasis compared to RS (for DFS: ROR, P = 0.000; RS, P = 0.027; for DMFS, ROR, P = 0.047; RS, P = 0.621). Patients with HR + /HER2- early-stage breast cancer was classified into the luminal A, luminal B, HER2-enriched, and basal-like subtypes by PAM50. Basal-like subgroups showed the shortest DFS and DMFS. A modified IHC-based surrogate for intrinsic subtype analysis improved the concordance with PAM50 from 66.7% to 73.6%, particularly for basal-like subtype identification. High level of TILs and high expression of immune genes predicted poor prognosis. Multi-factor Cox analysis showed that IHC-based basal-like markers were the only independent factors affecting DMFS., Conclusions: Prognosis is better evaluated by PAM50 ROR in early-stage HR + /HER2- breast cancer and significantly differs among intrinsic subtypes. The modified IHC-based subtype can improve the basal-like subtype identification of PAM50. High immunity status and IHC-based basal-like markers are negative prognostic factors., (© 2022. The Author(s).)

Background: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated., Methods: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m 2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea., Discussion: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea., Trial Registration: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020., (© 2022. The Author(s).)

Background: The 21-gene recurrence score (RS) assay has been recommended by major guidelines for treatment decision in hormone receptor (HR)-positive early breast cancer (EBC). However, the genomic assay is not accessible and affordable worldwide. Alternatively, an increasing number of studies have shown that traditional immunohistochemistry (IHC) can partially or even completely replace the role of the 21-gene genomic assay. Here, we developed and validated a predictive model (IHC3 model) combining the Ki-67 index, progesterone receptor (PR) expression, histologic grade, and tumor size to predict the recurrence risk of HR-positive EBC., Methods: The data from 389 patients (development set) with HR-positive, human epidermal growth factor receptor 2-negative, lymph node non-metastasized invasive breast cancer were used to construct the IHC3 model based on the Surexam ® 21-gene RS and the TAILORx clinical trial criteria. An additional 146 patients with the same characteristics constituted the validation set. The predictive accuracy of the IHC3 model was compared with that of Orucevic et al.'s nomogram. Invasive disease-free survival (IDFS) was analyzed in the IHC3 predictive low-recurrence risk (pLR) group and the predictive high-recurrence risk (pHR) group. The Pearson chi-square test, Fisher exact test, and log-rank test were used for analysis., Results: The pLR and pHR group could be easily stratified using the decision tree model without network dependence. The accuracies of the IHC3 model were 86.1% in the development set and 87.7% in the validation set. The predictive accuracy of the IHC3 model and Orucevic et al.'s nomogram for the whole cohort was 86.5% and 86.9%, respectively. After a 52-month of median follow-up, a significant difference was found in IDFS between of the IHC3 pLR and the pHR groups (P = 0.001) but not in the IDFS between the low- and high-recurrence risk groups according to the Surexam® 21-gene RS and the TAILORx clinical trial criteria (P = 0.556) or 21-gene binary RS group (P = 0.511)., Conclusions: The proposed IHC3 model could reliably predict low and high recurrence risks in most HR-positive EBC patients. This easy-to-use predictive model may be a reliable replacement for the 21-gene genomic assay in patients with EBC who have no access to or cannot afford the 21-gene genomic assay., (© 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

We aimed to determine whether the detection-to-treatment interval of non-symptomatic breast cancer is associated with factors that can predict survival outcomes. A retrospective review of the Breast Surgery Department Database at Peking Union Medical College Hospital (PUMCH) was performed, and a total of 1084 non-symptomatic invasive breast cancer patients were included. The findings revealed that detection-to-treatment interval was significantly longer for women who were older (p = 0.001), lived in rural areas (p = 0.024), had lower education (p = 0.024), and had detection in other institutions (p = 0.006). Other sociodemographic and clinicopathological characteristics were not associated to longer interval. A median follow-up of 35 months (range: 6-60 months) was carried out and a long delay at more than 90 days did not significantly decrease the DFS (univariate, P = 0.232; multivariate, P = 0.088). For triple negative breast cancer, there was a worse DFS if the interval was longer than 90 days both in multivariate analysis (hazard ratio [HR] = 3.40; 95% CI, 1.12-10.35; P = 0.031) and univariate analysis (HR = 2.86; 95% CI, 1.03-7.91; P = 0.042). Further studies on care before initial treatment of non-symptomatic breast cancers are warranted.

The present study was performed to investigate the biological functions of microRNA‑320a in human breast cancer and the underlying mechanisms. MicroRNA‑320a expression was downregulated in human breast cancer, compared with the normal control. Overexpression of microRNA‑320a induced apoptosis, and inhibited cell viability and invasion in MDA‑MB‑231cells while downregulation of microRNA‑320a reduced apoptosis, and increased cell viability and invasion in MDA‑MB‑231 cells. Then, overexpression of microRNA‑320a suppressed insulin‑like growth factor 1 receptor (IGF‑1R), p‑AKt and cyclin D1 protein expression in MDA‑MB‑231cells. In addition, the downregulation of microRNA‑320a induced IGF‑1R, p‑Akt and cyclin D1 protein expression in MDA‑MB‑231cells. Furthermore, the IGF‑1R inhibitor increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. The p‑Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. These results revealed that microRNA‑320a suppresses tumor cell growth and invasion of human breast cancer by targeting IGF‑1R.

Objectives: The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery., Methods: Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests., Results: Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions., Conclusions: The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery., Trial Registration: ClinicalTrial.gov NCT00418457.