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BackgroundThe latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction (BR) in China. We conducted this study to explore the current status of BR using LDF with/without implants.MethodsThis study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) between 2000 and 2021.ResultsWe analyzed 4918 patients who underwent postmastectomy BR, including 1730 patients (35.2%) with autologous flaps. LDF was used for BR in 1093 (22.2%) patients, and an abdominal flap was used in 637 (13.0%) patients. The proportion of LDFs used in autologous BR patients decreased each year and dropped to approximately 65.0% after 2013 due to the increased use of abdominal flaps. Among these patients, 609 underwent extended LDF (ELDF) BR, 455 underwent LDF BR with implants, and 30 received a LDF as a salvage flap due to previous flap or implant failure. Patients who underwent ELDF reconstruction were older and had a higher BMI than those who received a LDF with implants. There was no significant difference in the mean postoperative hospital stay, neoadjuvant chemotherapy rates, or adjuvant radiotherapy rates between the two groups. Major complications requiring surgical intervention occurred in 25 patients (2.29%). There was no significant difference in the incidence of major complications between the two groups (P=0.542).ConclusionsLDF breast reconstruction is a well-developed and safe procedure. The duration of postoperative hospitalization nor the incidence of major complications was affected by implant use.

BackgroundNeoadjuvant chemotherapy (NAC) has evolved significantly and has been widely accepted for downstaging disease in early-stage and locally advanced breast cancer patients. Since the optimal surgical intervention for patients receiving NAC remains controversial, we aim to investigate the survival outcome of patients treated with different surgical management.MethodsA retrospective, nested case-control study was conducted in patients with invasive breast cancer that underwent NAC at Fudan University Shanghai Cancer Center from January 2010 to June 2019. Based on surgical intervention, patients were divided into mastectomy and breast conservation groups. Patients were matched on age at diagnosis, menopausal status, the year of the surgery, post neoadjuvant therapy pathological tumor (ypT) stage, post neoadjuvant therapy pathological node (ypN) stage, molecular subtypes, and axillary surgery by propensity score matching.ResultsA total of 2080 patients were enrolled in this study. Among them, 1819 (87.5%) patients were categorized as mastectomy group, and 261 (12.5%) patients were classed as breast conservation group. Over 9-years of research, the proportion of breast conservation steadily increased in patients after NAC. Data showed that younger (P

BackgroundBreast cancer is one of the leading causes of cancer-related death among women, and the pathological status of axillary lymph nodes is an important predictor of prognosis. However, the mechanism involved in this early stage of metastasis remains largely unknown.MethodsMicroarray analysis was used to carry out differential genomics analyses between matched pairs of metastatic sentinel lymph node tissues and breast primary tumors. The CRISPR/Cas9 gene editing system was used for in vivo screening by transplanting a loss-of-function cell pool into immunocompromised mice. MAGeCK was used to analyze the screening results. Survival analysis was performed via the Kaplan–Meier method. Cell proliferation, wound healing, migration and invasion assays were performed to confirm the phenotype. A tail vein model and subcutaneous xenotransplanted tumor model were used for the in vivo study. The relationship between coiled-coil domain containing 102B (CCDC102B) and receptor for activated C kinase 1 (RACK1) was examined using coimmunoprecipitation, mass spectrometry, nuclear protein extraction and immunofluorescence assays. The primary biological functions and pathways related to CCDC102B were enriched by RNA sequencing.ResultsWe identified CCDC102B through screening and found that it was significantly upregulated in metastatic lesions in lymph nodes compared to matched primary tumors. Increased expression of CCDC102B promoted breast cancer metastasis in vitro and in vivo. Additionally, high expression of CCDC102B was correlated with poor clinical outcomes in breast cancer patients. We further identified that CCDC102B was stabilized by the loss of RACK1, a protein negatively correlated with breast cancer metastasis. Mechanistically, we found that RACK1 promoted CCDC102B lysosomal degradation by mediating chaperone-mediated autophagy (CMA). The aggressive behavior of CCDC102B in breast cancer cells could be reversed by the expression of RACK1. Moreover, CCDC102B was correlated with the significant enrichment of NF-κB pathway components. Overexpressing CCDC102B led to less interaction between RACK1 and IKKa. Thus, CCDC102B positively regulates the NF−κB pathway by interacting with RACK1.ConclusionTaken together, our findings uncover a novel role of CCDC102B in breast cancer metastasis. CCDC102B serves as a potential metastasis promoter by regulating the activation of the NF-κB pathway and can be degraded by RACK1 via CMA.

BackgroundMitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI’s efficacy and safety in sentinel lymph node biopsy (SLNB).MethodsThe trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥−5%.ResultsSLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up.ConclusionsMHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, CTR20192435.

BackgroundCompared with older patients, young women with breast cancer (YWBCs) have a poorer prognosis and a higher risk of recurrence. Ages ≤35 years are independent risk factors for local recurrence of breast cancer. Surgery is the most important local treatment for YWBC, and there is still a lack of prospective studies comparing surgical options for recurrence and survival. We retrospectively compared the effects of surgical options on disease-free survival (DFS) and overall survival (OS) of YWBC at Fudan University Shanghai Cancer Center (FUSCC).MethodsYWBCs (age ≤35 years) who underwent surgery at FUSCC between 2008 and 2016 were retrospectively analyzed and divided into three groups according to surgical options: 1) breast-conserving surgery (BCS), 2) mastectomy alone (M), and 3) mastectomy with reconstruction (RECON). The DFS and OS outcome rates from the three surgical options were compared using the Kaplan–Meier method and Cox regression model. Propensity score matching (PSM) was also used to balance the baseline characteristics to eliminate selection bias.ResultsA total of 1,520 YWBCs were enrolled with a median follow-up of 5.1 years, including 524 patients (34.5%) who underwent BCS, 676 patients (44.5%) who underwent M, and 320 patients (21.1%) who underwent RECON. The 5-year DFS rates were 96%, 87%, and 93%, respectively (P < 0.001); the 5-year OS rates were 98%, 94%, and 97%, respectively (P = 0.002). Multivariate Cox analysis showed that DFS and OS were significantly improved in patients undergoing BCS compared with those undergoing M, with hazard ratios (HR) of 0.448 (95% CI 0.276–0.728; P = 0.001) and 0.405 (95% CI 0.206–0.797, P = 0.009), respectively. After PSM, DFS and OS rates were significantly improved in patients undergoing BCS compared to patients undergoing M (DFS, P = 0.001; OS, P = 0.009); RECON was also improved compared to patients undergoing M in terms of DFS and OS, but the difference was not statistically significant (DFS, P = 0.164; OS, P = 0.130).ConclusionsThe surgical options were independent factors affecting DFS and OS in YWBC, and the DFS and OS rates were significantly improved in the BCS group compared to those in the M group. BCS is preferred for early YWBC, and RECON is the best option for remodeling the body images of YWBC who do not have breast-conserving conditions.

BackgroundLncRNAs have been shown to play critical roles in regulating tumorigenesis and tumor progression. Using LncRNAs to predict prognosis and therapeutic response to cancer treatment has been caused for concern, but the predictive value of lncRNAs remains to be explored and underlying mechanisms have not been completely understood.MethodsThe Linc01315 expression level was detected in 282 breast cancer tissues by using quantitative RT-PCR. The association between Linc01315 expression level and clinicopathological features of these breast cancer patients was further analyzed. Multiple regression analysis was used to evaluate Linc01315 predictive value of patients’ prognosis.ResultsOur study revealed that Linc01315 expression level was significantly correlated with vessel invasion (P = 0.028) and tumor subtype (P = 0.039). The Kaplan–Meier survival curves demonstrated that patients with lower Linc01315 expression level had significantly longer disease free survival (DFS) (P = 0.002) and overall survival (OS) (P=0.019). Multiple regression analysis showed that Linc01315 level could be an independent predictive factor for DFS (hazards ratio = 0.613, 95% confidence interval = 0.375-1.003; P = 0.049) and OS (hazards ratio = 0.439, 95% confidence interval = 0.228-0.845; P = 0.014). Further analysis showed that low Linc01315 level patients with endocrine therapy could benefit patients DFS (P=0.037) and OS (P=0.025).ConclusionOur results demonstrate that Linc01315 expression level is significantly correlated with breast cancer patients’ prognosis. Linc01315 may represent an independent prognostic marker and therapeutic target in breast cancer.

BackgroundThe genomic tests such as the MammaPrint and Oncotype DX test are being gradually applied for hormone receptor positive/HER-2 negative (HR+/HER2-) breast cancer patients with up to three positive axillary lymph nodes (ALNs). The first results from RxPONDER trial suggested that Oncotype DX could be applied to patients with 1-2 positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND), which constituted 37.4% of the intent-to-treat population. However, there was no distinctive research on how to apply genomic tests precisely to HR+/HER2- patients with 1-2 positive SLNs without ALND. The purpose was to construct a nomogram using the multi-center retrospective data to predict precisely which HR+/HER2- candidates with 1-2 positive SLNs could be subjected to genomic tests (≤ 3 positive lymph nodes).MethodsWe conducted a retrospective analysis of 18,600 patients with stage I-III breast cancer patients treated with sentinel lymph node biopsy (SLNB) in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. The univariate and multivariate logistic regression analysis was conducted to identify the independent predictive factors of having ≤ 3 positive nodes among patients with 1-2 positive SLNs. A nomogram was developed based on variables in the final model with p

BackgroundLoco-regional recurrences (LRR) following breast-conserving surgery (BCS) remain a heterogeneous class of disease that has significant variation in its biological behavior and prognosis.MethodsTo delineate the spatiotemporal patterns of LRR after BCS, we analyzed the data of 4325 patients treated with BCS from 2006 to 2016. Clinico-pathological and treatment specific factors were analyzed using the Cox proportional hazards model to identify factors predictive for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype.ResultsWith a median follow-up of 66 months, 120 (2.8%) LRRs were recorded as the first site of failure. Age, pathologic stage, and molecular subtype were identified as predictors of LRR. The major recurrence type was ipsilateral breast tumor recurrence, which mainly (83.6%) occurred ≤5y post surgery. In the overall population, ARR curves showed that relapse peaked in the first 2.5 years. Patients with regional nodal recurrence, shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2-positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery.ConclusionsLRR risk following BCS is generally low in Chinese ethnicity. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.

BackgroundTrastuzumab shows excellent benefits for HER2+ breast cancer patients, although 20% treated remain unresponsive. We conducted a retrospective cohort study to optimize neoadjuvant chemotherapy and trastuzumab treatment in HER2+ breast cancer patients.MethodsSix hundred patients were analyzed to identify clinical characteristics of those not achieving a pathological complete response (pCR) to develop a clinical predictive model. Available RNA sequence data was also reviewed to develop a genetic model for pCR.ResultsThe pCR rate was 39.8% and pCR was associated with superior disease free survival and overall survival. ER negativity and PR negativity, higher HER2 IHC scores, higher Ki-67, and trastuzumab use were associated with improved pCR. Weekly paclitaxel and carboplatin had the highest pCR rate (46.70%) and the anthracycline+taxanes regimen had the lowest rate (11.11%). Four published GEO datasets were analyzed and a 10-gene model and immune signature for pCR were developed. Non-pCR patients were ER+PR+ and had a lower immune signature and gene model score. Hormone receptor status and immune signatures were independent predictive factors of pCR.ConclusionHormone receptor status and a 10-gene model could predict pCR independently and may be applied for patient selection and drug effectiveness optimization.

Background: Neoadjuvant chemotherapy (NAC) has evolved significantly and has been widely accepted for downstaging disease in early-stage and locally advanced breast cancer patients. Since the optimal surgical intervention for patients receiving NAC remains controversial, we aim to investigate the survival outcome of patients treated with different surgical management. Methods: A retrospective, nested case-control study was conducted in patients with invasive breast cancer that underwent NAC at Fudan University Shanghai Cancer Center from January 2010 to June 2019. Based on surgical intervention, patients were divided into mastectomy and breast conservation groups. Patients were matched on age at diagnosis, menopausal status, the year of the surgery, post neoadjuvant therapy pathological tumor (ypT) stage, post neoadjuvant therapy pathological node (ypN) stage, molecular subtypes, and axillary surgery by propensity score matching. Results: A total of 2080 patients were enrolled in this study. Among them, 1819 (87.5%) patients were categorized as mastectomy group, and 261 (12.5%) patients were classed as breast conservation group. Over 9-years of research, the proportion of breast conservation steadily increased in patients after NAC. Data showed that younger (P<0.001) and pre-menopausal (P<0.001) patients with normal BMI (P=0.022) were more likely to receive breast conservation. Patients at advanced ypT stage (P<0.001), ypN stage (P<0.001), and clinical TNM stage (P<0.001) were more often to undergo mastectomy, while breast conservation rate was significantly higher in patients with triplenegative tumors (P=0.023). Compared with the mastectomy group, significant benefits in overall survival were observed in patients who received breast conservation (Hazard ratio 0.41, [95% confidence interval: 0.18-0.97]; p=0.049) in the matched cohort. There was no statistical difference between groups related to disease-free survival and locoregional recurrence. Conclusions: Tumor biology can significantly impact the surgical decision in patients administrated with NAC. Breast conservation was a safe alternative for mastectomy in the NAC setting without compromising survival outcomes and locoregional control. [ABSTRACT FROM AUTHOR]