Songjie Shen

A Prognostic Model of Triple-Negative Breast Cancer Based on miR-27b-3p and Node Status

Objective Triple-negative breast cancer (TNBC) is an aggressive but heterogeneous subtype of breast cancer. This study aimed to identify and validate a prognostic signature for TNBC patients to improve prognostic capability and to guide individualized treatment. Methods We retrospectively analyzed the prognostic performance of clinicopathological characteristics and miRNAs in a training set of 58 patients with invasive ductal TNBC diagnosed between 2002 and 2012. A prediction model was developed based on independent clinicopathological and miRNA covariates. The prognostic value of the model was further validated in a separate set of 41 TNBC patients diagnosed between 2007 and 2008. Results Only lymph node status was marginally significantly associated with poor prognosis of TNBC (P = 0.054), whereas other clinicopathological factors, including age, tumor size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and type of surgery, were not. The expression levels of miR-27b-3p, miR-107, and miR-103a-3p were significantly elevated in the metastatic group compared with the disease-free group (P value: 0.008, 0.005, and 0.050, respectively). The Cox proportional hazards regression analysis revealed that lymph node status and miR-27b-3p were independent predictors of poor prognosis (P value: 0.012 and 0.027, respectively). A logistic regression model was developed based on these two independent covariates, and the prognostic value of the model was subsequently confirmed in a separate validation set. The two different risk groups, which were stratified according to the model, showed significant differences in the rates of distant metastasis and breast cancer-related death not only in the training set (P value: 0.001 and 0.040, respectively) but also in the validation set (P value: 0.013 and 0.012, respectively). Conclusion This model based on miRNA and node status covariates may be used to stratify TNBC patients into different prognostic subgroups for potentially individualized therapy.

Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse

BackgroundThe specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear.Methods147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated.ResultsALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman’s rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2-△△C T value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001).ConclusionsThe ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.

NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells

Recently, the human gene NOTCH1 has been found to be implicated in cancer cell metastasis and the maintenance of cancer stem cells. However, for breast cancer in particular, an association between NOTCH1 levels and metastasis has not been determined. In this study, we investigated the expression status and correlation of NOTCH1 with clinically important factors related to metastasis and the cancer stem cell marker ALDH1. NOTCH1 and ALDH1 levels in 115 tumor tissues from primary lesions were determined by immunohistochemical staining. Most tissues were stained positive for both NOTCH1 and ALDH1, and NOTCH1 positivity was significantly associated with ALDH1 levels. NOTCH1 levels were significantly associated with TNM stage, metastasis, and triple-negative breast cancer. Moreover, both univariate and multivariate regression analyses revealed that basal-like features and NOTCH1 positivity were associated with disease-free survival as independent predictors. These analyses indicated that breast cancer patients testing positive for NOTCH1 had shorter disease-free survival. Our findings suggest that NOTCH1 may be involved in metastasis and is closely correlated with breast cancer stem cells.

Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized, Controlled, Single-Center Trial.

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

CTCs hemodialysis: Can it be a new therapy for breast cancer?

Circulating tumor cells (CTCs) play an important role in Blood-borne distant metastasis, which is the leading cause of cancer-related death in breast cancer. So far, the impacts of CTCs as a tool for predicting or monitoring the efficacy of systemic therapy and that it is a independent prognostic factor have been confirmed. However, CTCs cannot be generally removed at primary surgery or by systemic therapy. In some EMT (epithelial mesenchymal transition)-related treatment fail, CTCs can be accumulated in the postoperative course of the patient which lead to a bad prognosis. In view of these, considering mature hemodialysis technology, we further propose CTCs hemodialysis (CHD), which filtrate CTCs out of blood, as a new therapy for the breast cancer.

Clinicopathological characteristics and long-term prognosis of screening detected non-palpable breast cancer by ultrasound in hospital-based Chinese population (2001-2014)

Purpose The mainstay modality of breast cancer screening in China is the hospital-based opportunistic screening among asymptomatic self-referred women. There is little data about the ultrasound (US) detected non-palpable breast cancer (NPBC) in Chinese population. Methods We analyzed 699 consecutive NPBC from 1.8-2.3 million asymptomatic women from 2001 to 2014, including 572 US-detected NPBC from 3,786 US-positive women and 127 mammography (MG) detected NPBC from 788 MG-positive women. The clinicopathological features, disease-free survival (DFS) and overall survival (OS) were compared between the US- and MG-detected NPBC. Prognostic factors of NPBC were identified. Results Compared to MG, US could detect more invasive NPBC (83.6% vs 54.3%, p<0.001), lymph node positive NPBC (19.1% vs 10.2%, p=0.018), lower grade (24.8% vs 16.5%, p<0.001), multifocal (19.2% vs 6.3%, p<0.001), PR positive (71.4% vs 66.9%, p=0.041), Her2 negative (74.3% vs 54.3%, p<0.001), Ki67 high (defined as >14%, 46.3% vs 37.0%, p=0.031) cancers and more NPBC who received chemotherapy (40.7% vs 21.3%, p<0.001). There was no significant difference in 10-year DFS and OS between US-detected vs MG-detected NPBC, DCIS and invasive NPBC. For all NPBC and the US-detected NPBC, the common DFS-predictors included pT, pN, p53 and bilateral cancers. Conclusion US could detect more invasive, node-positive, multifocal NPBC in hospital-based asymptomatic Chinese female, who could achieve comparable 10-year DFS and OS as MG-detected NPBC. US would not delay early detection of NPBC with improved cost-effectiveness, thus could serve as the feasible initial imaging modality in hospital-based opportunistic screening among Chinese women.

Prognosis of subtypes of the mucinous breast carcinoma in Chinese women: a population-based study of 32-year experience (1983-2014)

Purpose The heterogeneous nature of the mucinous breast cancer (MBC), with its pure (PMBC) and mixed subtypes (MMBC), calls for precise prognosis assessment. Methods We analyzed 197 consecutive MBC patients, including 117 PMBC and 80 MMBC, who were treated from 1983 to 2014. The clinicopathological features, treatment choice, disease-free survival (DFS) and overall survival (OS) were compared among PMBC, MMBC and MMBC subgroups. Prognostic factors of PMBC and MMBC were identified. Results Compared to PMBC, MMBC had more lymph node metastasis (p = 0.043), Her2 positivity (p = 0.036), high Ki-67 index (defined as>20%, p = 0.026) and anti-Her2 targeted therapy (p = 0.016). The 5-year DFS of PMBC and MMBC were 90.4% and 86.2%, whereas the 5-year OS were 99.0% and 98.7%. No significant difference was found in DFS or OS among all MBC subtypes. High Ki-67 (p = 0.020) appeared as DFS factor in PMBC, while anti-Her2 targeted therapy (p = 0.047) as the DFS predictors in MMBC. Conclusion MMBC manifested similar 5-year survival to PMBC in Chinese woman, suggesting that intra-tumoral heterogeneity might not interfere with MBC short-term prognosis.

Mammography-detected ultrasound-negative asymptomatic micro-calcifications in Chinese women: Would it be safe to watch and wait?

Although mammography (MG) has been widely used for breast cancer screening in the western world, over-diagnosis remains controversial. Milestone studies showed that ultrasound (US) was an effective primary screening test for breast cancer both in the western world and in China. US improves the sensitivity of screening in Chinese women who have denser breasts and develop breast cancer earlier than Caucasian counterparts, and is used as the primary imaging test in the hospital-based opportunistic screening among asymptomatic self-referred women. Our previous work showed that US result might further differentiate the MG-detected breast cancers into low risk (US+) and ultra-low risk (US-). Indeed, most of the MG+/US- breast cancers would be ultra-low risk cancers and almost always present as MG micro-calcifications. Furthermore, majority of the commonest MG+/US- abnormal finding of micro-calcification is usually benign. Biopsy of benign breast disease increases not only the risk of breast cancer, but the expenses of screening and healthcare. Our hypothesis proposes that mammography-positive ultrasound-negative (MG+/US-) asymptomatic micro-calcifications might not need immediate invasive procedures and be safe to observe until the micro-calcifications increase significantly or become US-positive. If this hypothesis is proved, US would serve as the primary imaging test for breast cancer screening in China, with MG as the selective screening test and diagnostic tool for surgical plan. Unnecessary biopsy or surgery might be avoided with screening expenses considerably decrease.

Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer

There were limited data available for a head‐to‐head comparison of the identification rate and survival between the combined method of indocyanine green fluorescence and blue dye versus the traditional blue dye alone method for sentinel lymph node (SLN) biopsy.

Would 1.0 cm be a more suitable cutoff to subdivide pT1 tumors in hormone receptor-negative and HER2-positive breast cancer?

HER2+ and hormone receptor (HoR)‐negative breast cancer usually associated with poor outcome. However, it remained elusive for the prognosis of small (T1a‐T1c) HER2+/HoR‐ breast cancer. The present study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database to explore the clinicopathological characteristics and prognosis of T1a‐T1c HER2+/HoR‐ breast cancer.