Locoregional recurrence and survival of breast-conserving surgery compared to mastectomy following neoadjuvant chemotherapy in operable breast cancer.

Background: The risk of locoregional recurrence (LRR) and the long-term prognosis of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) are still controversial. This study aimed to evaluate oncological outcomes for patients undergoing BCS after NAC and determine LRR and survival predictors. Methods: This study was a retrospective cohort study of patients with locally advanced breast cancer (LABC) who received NAC and underwent BCS or mastectomy from June 2011 to November 2020. LRR, disease-free survival (DFS), and overall survival (OS) were compared in patients undergoing BCS or mastectomy. Univariate and multivariate analyses were performed to determine LRR, DFS, and OS predictors. Results: A total of 585 patients were included, of whom 106 (18.1%) underwent BCS and 479 (81.9%) underwent a mastectomy. The LRR rate was 11.3% in the BCS group and 16.3% in the mastectomy group, revealing no significant difference(p = 0.200). In patients who underwent BCS, clinical lymph node status, histological grade and pathological complete response (pCR) were independent factors to predict LRR. There was no significant difference in DFS and OS between the BCS and the mastectomy groups. Multivariable analysis showed that lymph node status, histological grade, molecular subtypes, pCR and Miller&Payne (M&P) classification were independent predictors of DFS. Lymph node status, molecular subtypes and pCR were independent predictors of OS. BCS or mastectomy was not an independent predictor of DFS or OS. Conclusion: Compared with mastectomy, BCS after NAC may not increase the risk of local recurrence or mortality, BCS can be performed in selected patients with small tumor size and good response to NAC.

Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial.

OBJECTIVE: To assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive metastatic breast cancer. DESIGN: Randomised, double blind, placebo controlled, multicentre, phase 3 trial. SETTING: 40 centres in China between 6 May 2019 and 17 January 2022. PARTICIPANTS: 590 female patients (median age 52 (interquartile range 46-58) years) with untreated HER2 positive metastatic breast cancer. INTERVENTIONS: Eligible patients were randomised 1:1 to receive either oral pyrotinib (400 mg once daily) or placebo, both combined with intravenous trastuzumab (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day cycle. Randomisation was stratified by treatment history of trastuzumab in the (neo)adjuvant setting and hormone receptor status. Patients, investigators, and the sponsor's study team were masked to treatment assignment. MAIN OUTCOME MEASURES: The primary endpoint was progression-free survival as assessed by the investigator. RESULTS: Of the 590 randomised patients, 297 received pyrotinib, trastuzumab, and docetaxel treatment (pyrotinib group), and 293 received placebo, trastuzumab, and docetaxel treatment (placebo group). At data cut-off on 25 May 2022, the median follow-up was 15.5 months. The median progression-free survival according to the investigator was significantly longer in the pyrotinib group than in the placebo group (24.3 (95% confidence interval 19.1 to 33.0) months versus 10.4 (9.3 to 12.3) months; hazard ratio 0.41 (95% confidence interval 0.32 to 0.53); one sided P<0.001). Treatment related adverse events of grade 3 or higher were reported in 267 (90%) of the 297 patients in the pyrotinib group and 224 (76%) of the 293 patients in the placebo group. No treatment related deaths occurred in the pyrotinib group, and one (<1%; diabetic hyperosmolar coma) treatment related death occurred in the placebo group. Survival and toxicities are still under assessment with longer follow-up. CONCLUSIONS: Pyrotinib, trastuzumab, and docetaxel showed superiority by significantly improving progression-free survival compared with placebo, trastuzumab, and docetaxel in patients with untreated HER2 positive metastatic breast cancer. The toxicity was manageable. The findings support this dual anti-HER2 regimen as an alternative first line treatment option in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03863223.

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.

IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

Predictive and prognostic effect of HO-1 expression in breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: Heme oxygenase-1 (HO-1) has complex biological function, and is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we evaluated the relationship between expression of HO-1 protein with clinical response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We used immunohistochemistry (IHC) to determine expression of HO-1 protein from core needle biopsy before NAC, then applied univariate and multivariate analyses to understand the relationship between HO-1 with pathological complete response (pCR) outcomes. Next, Kaplan-Meier and Log-rank tests were used to compare disease-free survival (DFS) and overall survival (OS), between groups, and Cox proportional hazards regression analysis applied for prognostic evaluation. RESULTS: A total of 575 patients with locally advanced invasive breast cancer were included in the study, of which 111 (19.3%) achieved pCR after NAC. Results from multivariate analysis showed that high HO-1 expression was an independent predictor of low pCR rate (OR 0.254, 95% CI 0.026-0.643, p = 0.002). Moreover, results from survival analysis showed that high HO-1 expression was significantly associated with shorter DFS (HR 4.843, 95% CI 1.205-32.572, p = 0.026), but not with OS (HR 3.219, 95% CI 0.928-32.124, p = 0.071). Furthermore, HO-1 expression was significantly associated with lower pCR rate (OR 0.102, 95% CI 0.013-0.352), p = 0.001), poor DFS (HR 8.562, 95% CI 1.592-34.950, p = 0.009), and OS (HR 7.835, 95% CI 1.220-56.213, p = 0.023) of patients with triple-negative breast cancer (TNBC) patients. CONCLUSION: Our results indicated that HO-1 expression is not only a biomarker for predicting pCR, but also a prognostic factor in breast cancer patients in a neoadjuvant setting, especially in TNBC subgroups.

Perceived Importance of Breast Cancer Risk Factors: A Survey on 386 Physicians in China.

There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience.  This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.

Significance of Oncotype DX 21-Gene Test and Expression of Long Non-Coding RNA MALAT1 in Early and Estrogen Receptor-Positive Breast Cancer Patients.

OBJECTIVE: To investigate the association between the recurrence score (RS) obtained by Oncotype DX 21-gene test and long non-coding RNA (lncRNA) MALAT1 expression in early and estrogen receptor-positive (ER+) breast cancer. MATERIALS AND METHODS: The Oncotype DX 21-gene test and MALAT1 expression detection were performed in tumor samples from 76 ER+ and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of MALAT1 was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann-Whitney U-test or Kruskal-Wallis test were used to analyze the association between MALAT1 level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman's rank correlation analysis. RESULTS: The expression of MALAT1 was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641±1.438, Z=-2.594, p=0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS<18), 36.8% of patients were in medium risk (18≤RS≤30), and 10.5% of patients were in high risk (RS>30). While under the new criteria, 18.4% were in low risk group (RS<11), 63.2% were in a medium risk group (11≤RS≤26), and 18.4% were in a high risk group (RS>26). The Oncotype DX 21-gene results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA MALAT1 was significantly correlated with the Oncotype DX 21-gene results under the old criteria. CONCLUSION: MALAT1 is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. MALAT1 level is associated with the Oncotype DX 21-gene RS value. Therefore, combination of MALAT1 and the Oncotype DX 21-gene test may be used to predict prognosis in ER+ and early stage breast cancer.

Impact of Primary Site Surgery on Survival of Patients with de novo Stage IV Breast Cancer.

PURPOSE: The efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer. MATERIALS AND METHODS: Women with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients. RESULTS: Two hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival. CONCLUSION: Surgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.

ALOX12 inhibition sensitizes breast cancer to chemotherapy via AMPK activation and inhibition of lipid synthesis.

Arachidonate lipoxygenase12 (Alox12) and its metabolites 12S-hydroxyeicosatetraenoic acid (12S-HETE) have been implicated in influencing tumor transformation and progression. In this study, we have systematically evaluated the expression, function and the downstream effectors of Alox12 in breast cancer using loss- and gain-of-function approaches. We demonstrated that both mRNA and protein levels of Alox12 were significantly increased in multiple breast cancer cell lines compared to normal breast cells. The upregulation of Alox12 expression was also observed in breast cancer tissues and their matched normal breast tissues obtained from patients. Functionally, we demonstrated that Alox12 overexpression was sufficient to stimulate growth in normal breast cells but not breast cancer cells. This also protects breast cancer cell from chemotherapy-induced growth arrest and apoptosis. In contrast, Alox12 depletion inhibited breast cancer growth and survival, and significantly enhanced the chemotherapeutic agents' efficacy. Mechanism studies showed that Alox12 depletion activated AMP-activated protein kinase (AMPK), leading to the inhibition of acetyl-CoA carboxylase1 (ACC1) enzyme activity and lipid synthesis. The recuse of the effects of Alox12 depletion using Alox12 metabolites 12S-HETE further confirmed that AMPK and its subsequent inhibition of ACC1 activity and lipid synthesis were the downstream signaling of Alox12 inhibition. Our findings highlighted the important role of Alox12 in breast cancer, particularly in response to chemotherapy. Our work also demonstrate that inhibiting Alox12 is a possible alternative therapeutic strategy to overcome chemoresistance in breast cancer.

Efficacy of Iodine-125 Seed Implantation in Locoregionally Recurrent and Unresectable Breast Cancer: a Retrospective Study.

The management of locoregionally recurrent and unresectable breast cancer is a therapeutic challenge. This retrospective study aimed to assess the efficacy of 125I seed implantation brachytherapy as a palliative management in locoregionally recurrent breast cancer. We analyzed 36 locoregionally recurrent and unresectable breast cancers in our hospital between 2012 and 2016. All patients were treated with CT-guided 125I seed permanent implantation. The dose distribution of 125I seeds was calculated using a computerized treatment planning system. Complete response, partial response, stable disease, and local tumor control rates were calculated. Long-term efficacy was assessed based on survival rates ranging from 1 to 4 years. The follow-up period ranged from 6 to 53 months. The median local control was 28 months (95% CI: 16.2-39.8 months). The percentage of patients who showed 6-month, 1-year, 2-year, and 3-year local control was 97.2%, 77.8%, 52.8%, and 33.3%, respectively. Median survival time for all patients was 48 months (95% CI: 40.9-55.1 months); 1-year, 2-year, 3-year, and 4-year survival rates were 97.2%, 80.6%, 63.9%, and 46.5%, respectively. Pain relief response rate was 88.9%. No serious complications were detected during the follow-up period. The results of this study demonstrate that 125I seed implantation could be considered a feasible and promising minimally invasive therapy for locoregionally recurrent and unresectable breast carcinoma.

Elevated expression of POLD1 is associated with poor prognosis in breast cancer.

Polymerase δ catalytic subunit gene 1 (POLD1) may serve an important function in the development of tumors. However, its role in breast cancer remains unclear. The aim of the present study was to observe the expression and the function of POLD1 in breast cancer. A total of 84 patients with invasive breast carcinoma were recruited between 2011 and 2013. The expression of POLD1 was detected in paired tumor and adjacent normal tissues. Gene expression level of POLD1 was assessed using reverse transcription quantitative polymerase chain reaction. The protein expression of POLD1 was assessed using western blot analysis. The association between the clinicopathological features of patients with breast cancer and POLD1 expression was analyzed using a χ2 test. Disease-free survival (DFS) was analyzed using Kaplan-Meier method, and Cox regression analysis was performed to investigate clinicopathological significance of POLD1 expression. Additionally, the effects of POLD1 in regulating cell cycle and proliferation of MCF-7 cells were evaluated in vitro. The results demonstrated that gene and protein expression levels of POLD1 were significantly elevated in breast cancer tissues compared with those in adjacent normal tissues. Increased expression of POLD1 was significantly associated with positive lymph node status (P=0.028), histological grade (P=0.025), p53 status (P<0.001) and ki-67 index (P=0.020). Survival analysis demonstrated that increased expression of POLD1 was associated with poor DFS (P=0.033). Additionally, increased expression of POLD1 was associated with shorter DFS at early-stage (P=0.037), late-stage cases (P=0.023) and with the presence of triple-negative tumors (TNBC; P=0.049). Multivariate analysis revealed that POLD1 may be used as an independent prognostic factor in patients with breast cancer. In vitro studies revealed that downregulation of POLD1 suppressed cell cycle progression and proliferation in MCF-7 cells. In conclusion, POLD1 may be considered as a potential prognostic marker for invasive breast carcinoma.

SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1).

Sirtuin 1 (SIRT1), class III histone deacetylase, plays an important character in cell proliferation, cell cycle, apoptosis, energy metabolism and DNA repair. In recent years, researchers have attached increasing attention on the role of SIRT1 in tumorigenesis, development and drug resistance. The effect of SIRT1 on breast cancer is still controversial and its exact role remains to be elucidated. In the present study, we investigated the significant role of SIRT1 in breast cancer by exploring the effect of SIRT1 on DNA polymerase delta1 (POLD1), the gene coding for DNA polymerase δ catalytic subunit p125. Immunohistochemistry showed that the protein expression level of SIRT1 was higher in breast cancer tissues relative to adjacent normal tissues. Knockdown of SIRT1 by shRNA decreased the proliferation, migration, and invasion of human breast cancer cell line MCF-7, while the overexpression of SIRT1 promoted the proliferation, migration, and invasion of MCF-7 cells. Clinically, the immunohistochemistry results revealed that the expression of SIRT1 was positively correlated with p125. Further analysis demonstrated that silencing of SIRT1 increased the expression of p53, while the expression level of POLD1/p125 decreased, and the result by overexpressing SIRT1 was opposite. Collectively, these data suggest that SIRT1 is an oncogenic factor in breast cancer cells and can be involved in the progression of breast cancer by inhibiting p53 and activating POLD1. Our finding provides new insights into the mechanisms of breast cancer.

Prediction of neoadjuvant chemotherapy response using diffuse optical spectroscopy in breast cancer

Purpose. Near-infrared diffuse optical spectroscopy (DOS) has been recently used to predict neoadjuvant chemotherapy response (NAC). In the present study, we explore the change in blood-oxygen content using DOS to predict NAC response against breast cancer. Materials and methods. A total of 20 patients were enrolled and underwent DOS scan with blood-oxygen detection before each treatment cycle. The first DOS scan was performed before NAC treatment (pretreatment), and subsequent scans were performed after each NAC treatment circle. Changes in blood content and oxygen content by DOS were evaluated and compared with tumor size, and their changes were analyzed in response versus nonresponse group. Results. Thirteen patients were classified into response and seven patients into nonresponse group. The tumor blood content value (−1.06 ± 0.43) and oxygen content value (0.48 ± 0.17) of DOS at pretreatment was significantly different from presurgery in response group (P < 0.05), but not in nonresponse group. In response group, the percentage change in blood content (median 91.19%) was significantly larger than tumor size (median 48.89%) (P = 0.0035), while in oxygen content (median 47.11%) is not (P = 0.2815). Comparing each cycle, the percentage change in blood content could distinguish responder from non-responder as early as after the first treatment cycle (19.1 versus 6.6%, P = 0.0265). Blood content percentage sensitivity was 76.9% and specificity was 85.7% (AUC 0.912), while oxygen content percentage sensitivity was 76.9% and specificity was 71.4% (AUC 0.797). Conclusion. Both blood and oxygen content measured by DOS could be used to discriminate responder to the treatment versus non-responder. Among the two, percentage change of blood content was more precise and earlier than that of oxygen content to predicted breast tumor response. The percentage change in blood content could distinguish responder from non-responder after the first treatment cycle (AU)

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Oncological safety of nipple-sparing mastectomy in young patients with breast cancer compared with conventional mastectomy.

Although nipple-sparing mastectomy (NSM) is being used more frequently, the oncological safety of NSM remains unclear, particularly in young patients (<35 years). The aim of the present study was to compare the rates of local recurrence (LR), disease-free survival (DFS) and overall survival (OS) in young patients with breast cancer who had undergone NSM or conventional mastectomy (CM). The clinicopathological data of young patients with stage 0-IIB breast cancer who had undergone NSM (163 cases) or CM (194 cases) between 2007 and 2016 were retrospectively analyzed. The log-rank test was used to analyze the differences in the LR, DFS and OS rates between the two groups and multivariate analysis was used to analyze the patient prognostic factors for DFS. The median follow-up time was 49 months. Patients who had undergone CM were more likely to exhibit stage II disease (68.4 vs. 58.3%; P=0.015) and positive lymph nodes (45.9 vs. 33.1%; P=0.014). In the NSM group, LR occurred in 7 (4.3%) cases, systemic recurrence in 15 (9.2%) cases and mortality in 9 (5.5%) cases. In the CM group, LR occurred in 6 (3.1%) cases, systemic recurrence in 27 (13.9%) cases and mortality in 15 (7.7%) cases. There were no statistical differences in the LR, DFS and OS rates between the two groups (P>0.05). Following adjustment for clinical stage, the LR and DFS rates between the two groups exhibited no significant differences. Analysis of the prognostic factors demonstrated that clinical stage, lymph node status, estrogen and progesterone receptor status and human epidermal growth factor receptor 2 status were associated with DFS (P<0.05). NSM is safe for young patients with early-stage breast cancer and provides patients with an improved cosmetic outcome. Furthermore, nipple-areola complex preservation does not increase the risk of recurrence.

Postoperative outcomes of breast reconstruction after mastectomy: A retrospective study.

Breast reconstruction after mastectomy plays an active role in improving the quality-of-life (QoL) and alleviating the psychological trauma of breast cancer patients, and has become an indispensable part of the comprehensive treatment in breast cancer. However, compared with mastectomy alone, breast reconstruction also increase operative complications. The surgical, oncological outcomes, and cosmetic effect of breast reconstruction remains to be evaluated. Data for patients with breast cancer who underwent breast reconstruction after mastectomy from February 2009 to November 2015 in our hospital were retrospectively analyzed, with a median follow-up time of 44 months. The operating time, blood loss, drainage fluid, postoperative complications, postoperative cosmesis, oncological outcomes, and QoL were evaluated and compared between different reconstruction types. A total of 151 women were included. The flap-based group had higher complication rates of marginal necrosis of incision, while the incidence of capsular contracture was higher in immediate implant group. There was no difference in blood loss, drainage fluid, and other postoperative complications. Several independent factors were associated with increased postoperative complications included diabetic, obese, and reconstruction with flap. There was no significant difference in the disease-free survival rate and overall survival rate between different surgical groups. In terms of cosmetic effect, patients in the tissue expander group were more likely to get a satisfactory postoperative breast appearance. QoL outcomes shown that the tissue expander group has better body image and sexual enjoyment, while there was no significant difference for other QoL domains. In conclusion, different methods of breast reconstruction are safe and feasible for patients with breast cancer, tissue expander implantation following delayed implant breast reconstruction is a more effective treatment on cosmetic and QoL outcomes.

Prediction of neoadjuvant chemotherapy response using diffuse optical spectroscopy in breast cancer.

PURPOSE: Near-infrared diffuse optical spectroscopy (DOS) has been recently used to predict neoadjuvant chemotherapy response (NAC). In the present study, we explore the change in blood-oxygen content using DOS to predict NAC response against breast cancer. MATERIALS AND METHODS: A total of 20 patients were enrolled and underwent DOS scan with blood-oxygen detection before each treatment cycle. The first DOS scan was performed before NAC treatment (pretreatment), and subsequent scans were performed after each NAC treatment circle. Changes in blood content and oxygen content by DOS were evaluated and compared with tumor size, and their changes were analyzed in response versus nonresponse group. RESULTS: Thirteen patients were classified into response and seven patients into nonresponse group. The tumor blood content value (-1.06 ± 0.43) and oxygen content value (0.48 ± 0.17) of DOS at pretreatment was significantly different from presurgery in response group (P < 0.05), but not in nonresponse group. In response group, the percentage change in blood content (median 91.19%) was significantly larger than tumor size (median 48.89%) (P = 0.0035), while in oxygen content (median 47.11%) is not (P = 0.2815). Comparing each cycle, the percentage change in blood content could distinguish responder from non-responder as early as after the first treatment cycle (19.1 versus 6.6%, P = 0.0265). Blood content percentage sensitivity was 76.9% and specificity was 85.7% (AUC 0.912), while oxygen content percentage sensitivity was 76.9% and specificity was 71.4% (AUC 0.797). CONCLUSION: Both blood and oxygen content measured by DOS could be used to discriminate responder to the treatment versus non-responder. Among the two, percentage change of blood content was more precise and earlier than that of oxygen content to predicted breast tumor response. The percentage change in blood content could distinguish responder from non-responder after the first treatment cycle.

Development of video-assisted breast cancer surgery: Initial experience with a novel method for creating working space without prior liposuction.

Endoscopic techniques are promising in breast surgery. In order to create working space, liposuction is widely used in video-assisted breast surgery (VABS). However, the use of liposuction is likely associated with side effects that may partly limit the application of VABS. Therefore, a new technique of endoscopic axillary lymphadenectomy without prior liposuction was developed by our group. A total of 106 female patients underwent VABS, with special adaptation of the video-assisted surgical procedures previously described. Differing from other endoscopic surgery techniques, our adaptations of VABS included the selection of the working instruments, trocar placement, creation of working space, order of axillary lymph node dissection and method of mastectomy. The operative time was 50-180 min (mean, 85.5 min). The intraoperative blood loss ranged from 20 to 100 ml (mean, 48 ml). The mean lymph node number harvested was 11.5 (range, 6-31). No serious intra- or postoperative complications were recorded. There was no axillary tumor relapse, trocar site tumor implantation or upper limb edema. Without prior liposuction, our new technique of VABS reduced the blood loss volume, endoscopic surgery time, total volume of drainage fluid and, most importantly, the risk of port-site metastases. This new technique appears to have great clinical potential and good prospects for future endoscopic breast surgery development.

ß-Glucosidase inhibition sensitizes breast cancer to chemotherapy.

The resistance to therapy is a major clinical challenge for advanced stage breast cancer. Identification of novel potential therapeutic targets is needed to overcome chemoresistance. In this work, we identified a target that was critically involved in breast cancer growth and chemoresistance. We demonstrated that ß-glucosidase expression and activity were significantly upregulated in breast cancer tissues and a panel of cell lines compared to normal adjacent breast tissues and cell lines. ß-glucosidase overexpression activated PI3K/Akt/mTOR signalling, leading to increased cell growth. In contrast, ß-glucosidase inhibition by siRNA depletion and pharmacological approach using conduritol B epoxide (selective ß-glucosidase inhibitor) suppressed growth and induced apoptosis in breast cancer cells. Importantly, ß-glucosidase inhibition significantly sensitized breast cancer cells to chemotherapy in vitro and in vivo, suggesting that inhibiting ß-glucosidase effectively targeted breast cancer cells that were resistant to elimination by chemotherapeutic agent alone. We demonstrated the positive role of ß-glucosidase in breast cancer growth and survival. Our work also suggested that inhibiting ß-glucosidase as a possible alternative therapeutic strategy to overcome chemoresistance in breast cancer.

Combination of 125I brachytherapy and chemotherapy for unresectable recurrent breast cancer: A retrospective control study.

Recurrent breast cancer remains an incurable malignancy and cannot be removed by surgery in the majority of cases. This study aimed to explore the feasibility and efficacy of the combination of I brachytherapy and chemotherapy for the treatment of unresectable recurrent breast cancer. Patients with unresectable recurrent breast cancer treated between January 2011 and December 2014 with a combination of I brachytherapy and capecitabine or gemcitabine were evaluated and outcomes were compared with those of women treated with capecitabine or gemcitabine in conventional dose as a monotherapy. Of 61 patients evaluated, 28 received the combination treatment and 33 received capecitabine or gemcitabine monotherapy. The combination of I brachytherapy and chemotherapy resulted in a significant improvement in progression-free survival versus capecitabine or gemcitabine monotherapy (median, 17.8 vs 11.4 months; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.84; P = 0.013). The objective response rate (ORR) was significantly higher with the combination (82.1%) than with monotherapy (54.5%; P = 0.022), and the rate of pain relief was higher in the combination arm (100% vs 73.6%; P = 0.038). There was no significant improvement for overall survival (median, 30.1 vs 27.2 months; HR, 0.82; 95% CI, 0.47-1.44; P = 0.496). There were no serious complications detected during the follow-up period, any grade toxicities were comparable between treatment arms. In conclusion, the combination of I brachytherapy and second-line chemotherapy is superior to chemotherapy alone and is an effective and safe therapy for unresectable recurrent breast cancer. However, further investigation and much larger scale randomized controlled trials with long-term follow-up are needed.

Harmonic Scalpel versus Electrocautery Dissection in Modified Radical Mastectomy for Breast Cancer: A Meta-Analysis.

BACKGROUND: Despite the common use of conventional electrocautery in modified radical mastectomy for breast cancer, the harmonic scalpel is recently emerging as a dominant surgical instrument for dissection and haemostasis, which is thought to reduce the morbidity, such as seroma and blood loss. But the results of published trials are inconsistent. So we made the meta-analysis to assess the intraoperative and postoperative endpoints among women undergoing modified radical mastectomy with harmonic scalpel or electrocautery. METHODS: A comprehensive literature search of case-control studies from PubMed, MEDLINE, EMBASE and Cochrane Library databases involving modified radical mastectomy with harmonic scalpel or electrocautery was performed. We carried out a meta-analysis of primary endpoints including postoperative drainage, seroma development, intraoperative blood loss and secondly endpoints including operative time and wound complications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the effect size for categorical outcomes and standardised mean differences (SMDs) for continuous outcomes. RESULTS: A total of 11 studies with 702 patients were included for this meta-analysis. There was significant difference in total postoperative drainage (SMD: -0.74 [95%CI: -1.31, -0.16]; P< 0.01), seroma development[OR: 0.49 (0.34, 0.70); P < 0.01], intraoperative blood loss(SMD: -1.14 [95%CI: -1.81,-0.47]; P < 0.01) and wound complications [OR: 0.38 (0.24, 0.59); P < 0.01] between harmonic scalpel dissection and standard electrocautery in modified radical mastectomy for breast cancer. No difference was found as for operative time between harmonic scalpel dissection and standard electrocautery (SMD: 0.04 [95%CI: -0.41, 0.50]; P = 0.85). CONCLUSION: Compared to standard electrocautery, harmonic scalpel dissection presents significant advantages in decreasing postoperative drainage, seroma development, intraoperative blood loss and wound complications in modified radical mastectomy for breast cancer, without increasing operative time. Harmonic scalpel can be recommended as a preferential surgical instrument in modified radical mastectomy.