Top PDF Targeted neoadjuvant therapy in the HER-2-positive breast cancer patients: a systematic review and meta-analysis

Targeted neoadjuvant therapy in the HER-2-positive breast cancer patients: a systematic review and meta-analysis

Targeted neoadjuvant therapy in the HER-2-positive breast cancer patients: a systematic review and meta-analysis

Pathological complete response (PCR) is defined as absence of invasive tumor cells in the breast. Tall PCR (tPCR) is defined as no invasive cancer in the breast and no pathological involvement axillary lymph node, which was analyzed based on hormone receptor (HR) status. Adverse events with III–IV grade include nausea, vomiting, diarrhea, hepatic toxicity, left ventricular ejection fraction (LVEF) decline, skin rash, and fatigue. The adverse effects were evaluated

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Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol

Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol

The present systematic review will evaluate the relative efficacy of various regimens used in neo-adjuvant set- ting. Further, it will also review the quality of evidence using GRADE approach [32]. To the best of our know- ledge, it will be the first study comparing the relative ef- ficacy of anthracycline- and taxane-based chemotherapy and targeted therapy regimens along with NACT in the management of breast cancer patients. Accordingly, it will facilitate evidence-based management of breast can- cer patients. Hence, this systematic review will be benefi- cial for wide audience including breast cancer patients, oncology professionals, insurers, policy makers, and re- searchers working in the field of oncology.
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Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis

Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis

95% CIs of relevant CVEs. CVEs Subjects and the total number of subjects in groups with AIs treatment were ex- tracted from the safety profiles of included trials to calculate CVEs incidence. The confidence level sets the boundaries of a confidence interval (CI), and it is conventionally set at 95% to coincide with the 5% convention of statistical significance in hypothesis testing. A 95% CI is the interval that you are 95% certain contains the true population value as it might be estimated from a much larger study. From each trial, we derived the proportion and 95% CI of patients developed CVEs. For trials with a control group, we further derived the OR of CVEs. For trials reporting no CVEs in any group, the OR and variance was obtained using classic half-integer con- tinuity correction. The data was tested for heterogeneity and among-study inconsistency using the Cochrane’s Q statistic and I 2 tests respectively [28, 29]. The statistical significance of heterogeneity was marked by a P < 0.1 or I 2 > 40%. The random-effects model was applied for data analysis when heterogeneity existed. Otherwise, a fixed-effects model was selected. A p-value<0.05 was considered statistically signifi- cant. The publication bias was estimated by the Begg’s and Egger’s test and a contour-enhanced funnel plots was con- ducted to futher evaluate the publication bias and enhance interpretation of a funnel plot by helping distinguish publication bias from other cause of funnel plot asymmetry [30–32]. Meta-Analyses (PRISMA) Statement was shown in the Additional file 5: Table S1. All data analyses were performed by using R software, version 3.2.3 (The R foun- dation for statistical computing, http://www.r-project.org) .
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Targeted therapy for HER2 positive breast cancer

Targeted therapy for HER2 positive breast cancer

Hurvitz et al. presented phase II data at ESMO 2011 and the data was subsequently published in 2013 [37]. The study showed that the patients treated with trastuzumab emtansine (T-DM1) achieved roughly a 40% reduction in risk of disease progression compared with those on a standard combination of trastuzumab plus docetaxel (14.2 months versus 9.2 months), (HR 0.59, P = 0.035) [37]. A total of 137 patients with locally advanced or metastatic HER2 positive breast cancer naive to chemotherapy or targeted therapy were exam- ined with a primary endpoint of progression-free sur- vival [37]. Overall, the toxicity was far lower among those on the investigational agent (46.4% versus 89.4%) and more women on standard care discontinued therapy due to side effects (28.8% versus 7.2%) [37]. Thus, it was concluded that first-line treatment with T-DM1 for pa- tients with HER2 positive metastatic breast cancer pro- vided a significant improvement in PFS, with a favorable safety profile, compared to standard combination ther- apy of trastuzumab plus docetaxel.
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Venous thromboembolism and mortality in breast cancer: cohort study with systematic review and meta analysis

Venous thromboembolism and mortality in breast cancer: cohort study with systematic review and meta analysis

There are several mechanisms via which a VTE may exert a detrimental impact on cancer survival. There is an im- mediate impact due to the known high short-term fatality resulting from a thrombotic event which among all pa- tients is estimated to be around 1% following a DVT and over 20% following a pulmonary embolism [41, 43]. Pooled results from two studies from the US and UK which would capture this short-term effect through in- corporating VTE as a time-varying covariate indicate a greater than 2-fold of risk of mortality following a VTE. Compliance with existing clinical guidelines on primary prevention of VTE in cancer patients which advise target- ing of prophylaxis in selected patients undergoing cancer surgery along with some patients in the outpatient setting [44–46]. However, it should be noted that in the Khorana score women with breast cancer may not be recom- mended for primary prophylaxis as these tend to score poorly on cancer type, anaemia and thrombocytosis. We have previously shown with this cohort that VTE events in women with breast cancer are likely to occur either
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Diffusion weighted imaging in monitoring the pathological response to neoadjuvant chemotherapy in patients with breast cancer: a meta analysis

Diffusion weighted imaging in monitoring the pathological response to neoadjuvant chemotherapy in patients with breast cancer: a meta analysis

A 2-by-2 contingency table separating patients into TP, TN, FP, and FN groups was constructed for each enrolled study. Based on this table, sensitivity and specificity were calcu- lated. Diagnostic odds ratio (DOR) was measured to esti- mate the effectiveness of DWI by calculating the odds of achieving pCR in patients with a positive test result to pa- tients with a negative test result. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was calculated to measure the performance of DWI. An AUC close to 1 indicates a favorable diagnostic performance, whereas a close to 0.5 AUC implies a poor test result. The Youden index (*Q), which is used in con- junction with SROC analysis and recognized as a preferred statistic to reflect the diagnostic value, were also assessed. A *Q index of 1 indicates a perfect test result. All data ana- lyses were carried out using statistical software package Meta-DiSc 1.4 and Stata version 15.0.
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HER 2 therapy  HER 2/neu diagnostics in breast cancer

HER 2 therapy HER 2/neu diagnostics in breast cancer

South San Francisco, CA, USA). Trastuzumab is a humanized recombinant mAb that specifically targets the HER-2/neu extracellular domain (ECD). The effectiveness of trastuzumab therapy has been proved not only in metastatic breast cancer (MBC) patients [1] but also in early-stage breast cancer patients receiving adjuvant trastuzumab therapy [2,3]. Recently, the US Food and Drug Administration (FDA) approved lapatinib [4] (Tykerb, GSK, Philadelphia, PA, USA) for clinical use. In addition, several tyrosine kinase inhibitors are currently in clinical development, including HKI-272, (Wyeth, Cambridge, MA, USA) [5] and AEE 788 (Novartis, Hanover, NJ, USA) [6]. Therefore, accurate determination of the HER-2/neu status is extremely important in guiding therapy, and the reliability of the diagnostic method used to determine HER-2/neu status is critical in selecting the most appropriate patients for HER-2/neu directed therapies. The present review is focused on HER-2/neu testing, and so we address reports concerning the tissue tests used to determine HER-2/neu status as well as tests to quantitate circulating levels of the HER-2/neu ECD. Although there is approximately 80% to 85% accuracy in determining HER-2/ neu status by tissue analysis, studies collectively show that the HER-2/neu status of the primary breast cancer (PBC) does not always accurately reflect the HER-2/neu status of the MBC. We highlight some of the factors that contribute to inaccurate assessment of HER-2/neu status by tissue testing, in the hope that this will improve assessment of HER-2/neu status. We also review reports on assays that have been used to quantitate circulating levels of the HER-2/neu ECD, and we present evidence that not all HER-2/neu assays have been adequately validated, which has resulted in inaccurate
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MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients

MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients

miRNAs analyzed correlated with drug response in HER2- negative patients, suggesting that miR-21 may be a specific biomarker of resistance for HER2-positive breast cancer (Table 1). A further analysis of an additional cohort of 30 HER2-positive breast cancers (Supplementary Table 1) confirmed that miR-21 overexpression was associated with RD ( p = 0.012) (Figure 1A), indicating that miR-21 is indeed involved in resistance to neoadjuvant treatment consisting of trastuzumab and chemotherapy. Notably, although the baseline levels of miR-21 predicted resistance to trastuzumab-chemotherapy treatment, we found that its expression was further upregulated after such therapy ( p = 0.016) (Figure 1B). These data indicate that an additional increase in miR-21 induced by the current therapy may sustain a molecular loop responsible for drug resistance in HER2-positive breast cancer. To further assess the ability of miR-21 to discriminate the patients’ responses to trastuzumab-based therapy, we performed a receiver- operating characteristic (ROC) analysis of the validation dataset. The results of this analysis confirmed that miR-21 expression was able to discriminate patients who achieved a pCR from those with RD after neoadjuvant therapy with high accuracy (AUC = 0.772) (Figure 1C).
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NatHER: protocol for systematic evaluation of trends in survival among patients with HER2-positive advanced breast cancer

NatHER: protocol for systematic evaluation of trends in survival among patients with HER2-positive advanced breast cancer

randomized clinical trials suggest that survival outcomes may be changing. For example, from June 1995 to March 1997, the phase III trial that supported the licen- sure of trastuzumab recruited patients with HER2- positive MBC (including patients with both HER2 im- munohistochemistry (IHC) 3+ and IHC 2+ tumors) who were not previously treated in the metastatic setting. Median OS among patients who received trastuzumab plus chemotherapy was 25.1 months compared with 20.3 months in the control arm [15]. Recruitment for the phase III CLEOPATRA study occurred between Feb- ruary 2008 and July 2010 [16]. The study included pa- tients with HER2-positive advanced breast cancer (IHC 3+ or amplification ratio ≥2.0 by fluorescence in situ hybridization) not previously treated in the metastatic setting. Median OS was 40.8 months in the control arm (trastuzumab plus docetaxel) and 56.5 months in the pertuzumab arm (pertuzumab plus trastuzumab plus do- cetaxel) [17]. This comparison across clinical trials, how- ever, is limited because of differences in study designs and patient populations. A comprehensive review and assessment of published interventional clinical trials is necessary to determine if a reliable change in outcomes exists.
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Oncological outcome of complete response after neoadjuvant chemotherapy for breast conserving surgery: a systematic review and meta analysis

Oncological outcome of complete response after neoadjuvant chemotherapy for breast conserving surgery: a systematic review and meta analysis

The following information was extracted from each eli- gible study: the first authors ’ names, the country in which the data were collected, the publication year, the applied neoadjuvant chemotherapy regimens, the total number of patients, mean age, tumor size, follow-up time, the number of patients who received BCS, the number patients who achieved CR, and the survival data (percentages and numbers of events) of BCS patients who achieved CR and those who did not. Other infor- mation was also recorded if the author found it useful. We used The Newcastle-Ottawa Scale (NOS) to assess the quality of each study by two authors. The scores in- cluded three parts: the selectivity of patients (0 – 4), com- parability of groups (0–2) and assessment of outcome (0 – 3). Scores > 5 were considered high-quality studies.
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Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: 
A systematic review and meta-analysis

Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: A systematic review and meta-analysis

Breast cancer (BC) is the most common type of cancer worldwide and is one of the leading causes of death in can- cer patients. Although the rate of BC is decreasing in de- veloped countries, it is rapidly increasing in developing countries (1, 2). Statistics show that every year more than one million new cases of cancer are diagnosed in the world and more than 400 000 people are lost to cancer (3). Early diagnosis and treatment of BC in its early stages could sig- nificantly increase the survival rate of BC patients (4). Trastuzumab in combination with chemotherapy has been
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Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial

Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial

Over 90% of the patients experienced a clinical objective response (CR or PR) assessed by palpation, ultrasonography and/or MRI. After 2 cycles and 4 cycles, the overall clinical response did not differ between two cohorts (Table 2). During the treatment, one patient in PEH group had tumor progress. Two patients in both cohorts underwent breast-conserving surgery (BCS). 18 (39.1%) of 46 patients in the PCH group and 20 (48.8%) of 41 patients in the PEH group achieved pCR (ypT0/ is, ypN0; OR 1.48 95%CI 0.63-3.47; p = 0.365).No significant difference was noted when other definitions of pCR (ypT0/is, ypN0/+) were used. Based on Miller & Payne grade, no significant difference in tumor regression was observed in both cohorts (p = 0.43). Performing subgroup analysis of patients in the PCH group, 13 (54.2%) of 24 patients who received 5/6 cycles of PCH achieved pCR, while 5 (22.7%) of 22 patients who received 4 cycles had pCR (p = 0.029). Whereas in PEH group, subgroup analysis revealed no significant difference in pCR rate in patients who were given different number of cycles of PEH (56.5% vs. 38.9%, p = 0.262). Univariate analysis for clinical characteristics predicting pCR was performed in whole patient population (S.Table 1), revealing no significant predictor for pCR. However, chemotherapy regimen (PCH vs. PEH) was found to be an independent factor associated with pCR in multivariate analysis (OR: 3.606, 95%CI: 1.153-11.274, p = 0.027). Figure2 showed the odd ratio (OR) of achieving pCR comparing PCH versus PEH with different characteristics. The results of this analysis revealed that treating patients with hormone receptor (HR) positive breast cancer with PEH regimen had a significantly higher chance to achieve pCR compared with PCH regimen (OR: 3.87, 95%CI: and safety. PEH might improve pCR rate, especially in the luminal-B subtype and
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Efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive breast cancer: a systematic review and meta-analysis

Efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive breast cancer: a systematic review and meta-analysis

We searched PubMed, Embase, and Cochrane databases from inception until July 1, 2017, for relevant articles in any language. The references were searched using a combination of medical subject heading terms and free text words, such as “breast neoplasm”, “breast cancer”, “breast carcinoma”, “neoadjuvant”, “preoperative”, “anthracycline”, “doxo- rubicin”, “epirubicin”, “Herceptin”, and “trastuzumab”. Two investigators independently performed the reference searches, and a third investigator was consulted when disagreement arose. More details of the search strategy are available in Supplementary materials.
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Negative genic switch of HER 2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2 positive breast cancer

Negative genic switch of HER 2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2 positive breast cancer

This case report highlights, in a neoadjuvant setting, the significance of further assessment of HER-2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor in order to formulate a more tailored adjuvant therapy, thus improving the patient’s outcome. Even if HER-2 gene status of synchronous nodal metastases undergoes nega- tive conversion, whether to adopt the protocol of trastuzumab-containing adjuvant therapy still remains un- certain, because we are still not sure whether it can com- pletely represent the characteristics of the distant metastatic cancer cells or CTCs. Prospective studies of HER-2 gene analyses among various matched lesions (i.e., primary tumors, synchronous nodal metastases, distant micro-metastases, and CTCs) in a neoadjuvant setting are needed for further study. Furthermore, a randomized con- trolled trial on whether to adopt the protocol of trastuzumab-containing adjuvant therapy among patients whose cancer lose HER2 expression not only in the pri- mary tumor but also in the synchronous metastatic nodal lesions after NAC should be carried out.
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Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis

Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis

Aromatase is a cytochrome P450 enzyme complex that is encoded by CYP19 located on chromosome 15q21.2 [11] and that catalyzes a critical reaction in estrogen biosyn- thesis involving the formation of aromatic C18 estrogens (estrone and estradiol) from C19 androgens (androstene- dione and testosterone) [12]. It is expressed especially in the ovaries as well as several extragonadal tissues (subcuta- neous fat, brain, liver, bone, vascular endothelial tissues, and the mesenchymal cells of the adipose tissue in the breast) [12]. Ma et al. [13] ‘resequenced’ all coding exons, all upstream untranslated exons plus their presumed core promoter regions, all exon-intron splice junctions, and a portion of the 3'-untranslated region of CYP19 using 240 DNA samples from patients of four ethnic groups and identified eighty-eight polymorphisms that resulted in 44 haplotypes. Many studies have reported an association be- tween BC risk and the CYP19A1 genotype [14–16].
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Targeted therapy in triple-negative metastatic breast cancer: a systematic review and meta-analysis

Targeted therapy in triple-negative metastatic breast cancer: a systematic review and meta-analysis

Despite these encouraging results, many unsolved questions remain regarding targeted therapies combined with CT in TNBC patients. There are still no answers for some important points: which is the most suitable chemotherapy scheme for the asso- ciation, which are the best molecular-targeted therapies, how to determine the ideal treatment sequence, and the real impact of using targeted therapy combined with CT in overall survival.

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Tumor-infiltrating Lymphocytes are Independent Favorable Prognostic Indicator in 17-year Disease-Free Survival in Lymph Node-Negative Triple-Negative Breast Cancer Patient

Tumor-infiltrating Lymphocytes are Independent Favorable Prognostic Indicator in 17-year Disease- Free Survival in Lymph Node-Negative Triple- Negative Breast Cancer Patient

In two meta-analyses, pooled analysis showed that dense TIL indicates high pathologic response rates to neoadjuvant chemotherapy and may lead to favorable outcomes. Authors concluded that TIL may be an independent and robust marker for the prediction of pathologic complete response (pCR) rate following neoadjuvant chemotherapy, mainly in TNBC [15,18]. The International TILs Working Group (2014) has recommended that TILs be standardized and assessed in breast cancer [23]. However, the 14 th St. Gallen International Breast Cancer Conference (2015), did not accept the presence of TILs as either a prognostic or predictive marker [47]. In the current cohort, the accurate assessment of pCR or lack of response to chemotherapy in 21 patients undergoing neoadjuvant chemotherapy was unfeasible. Sufficiently rigid criteria were not found in the histopathological case review for the evaluation and quantification of response.
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Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta analysis

Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta analysis

Pancreatic ductal adenocarcinoma (PDAC) portends an overall poor prognosis and is expected to become the second lethal malignancy in the USA by 2030 [1, 2]. Al- though surgery remains the only curative-intent treat- ment for PDAC, the management based on surgery first (SF) has not substantially improved the survival of patients with potentially resectable disease over the past two decades, even after the effort of adjuvant therapy (AT) [2–4]. The main reason is the early recurrence caused by micrometastases that were not undetected be- fore surgery [3, 5, 6]. Based on these clinical evidence to- gether with other preclinical evidence, PDAC even in early stage, analogous to breast cancer, should be recog- nized as a systemic disease [2, 7, 8]. Recently, neoadju- vant chemo(radio)therapy [NAC(R)T] is proposed as a new therapeutic strategy for early systemic treatment to increase completeness of resection (R0 rate) and control systemic micrometastases [3, 9]. The newest National Comprehensive Cancer Network (NCCN) guidelines, version 2.2018, recommended NACRT for the manage- ment of borderline resectable pancreatic cancer (BRPC). Also, NACRT is considered to be used in high-risk resectable pancreatic cancer (PRC). However, the recom- mendation of NCCN guidelines lacks high quality evi- dence [10, 11]. It is controversial for the application of NAC(R)T to RPC or BRPC in the real world, particularly in RPC, which is still intensely discussed at the European Society for Medical Oncology (EMSO) World Congress on Gastrointestinal Cancer 2019. Although there are several randomized controlled trials (RCTs) indicating NACRT increases survival in resectable or borderline re- sectable PDAC, the trials are limited by small sample sizes [9, 12]. It is still necessary to pool the existing stud- ies to perform a meta-analysis. Indeed, some scholars have done relevant meta-analyses, but most of them are single-arm meta-analyses, such as a recent meta-analysis by Versteijne et al. that lack direct comparison and ignore interstudy heterogeneity [11, 13, 14]. Other pub- lished meta-analyses did not focus on survival benefits [15]. Additionally, it is a fact that the definition of RPC and BRPC has undergone several changes over time, which leads to the existence of mixture of RPC and BRPC in the population of included studies according to current standard of resectability status. From this point of view, interstudy heterogeneity exists in all previous meta-analyses.
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Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta analysis of 5520 patients

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta analysis of 5520 patients

In addition, although the consensus guidelines at- tempt to separate patients into three distinct categories (R, BR and LA), in practice there can be some overlap between the BR and LA categories. At the extremes of BR and LA, the distinction is well- characterized, but there are several patients where the distinction is not that obvious (for example patients with approximately 180 degree involvement of SMA). Thus, some of the comparisons in the studies between the different categories need to be interpreted with caution. It also needs to be borne in mind that the adoption of FOLFIRINOX and gemcitabine-nab paclitaxel regimens is relatively recent (2011 and 2013) with lack of robust randomized controlled data. Our study used the Evans criteria for pooling the estimates of pathologic response [138]. Although Evans criteria remain the most widely used pathologic criteria for response assessment, Table 4 Surgical exploration and resection rates after neoadjuvant therapy
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Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for Her-2-positive breast cancer

Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for Her-2-positive breast cancer

Between October 2010 and December 2014, the Affiliated Cancer Hospital of Guangxi Medical University (Guangxi, China) enrolled 139 female patients whose age ranged from 27 to 70 years, with a median age of 47 years. All patients had no previous history of malignancy. All patients underwent a preoperative biopsy, breast ultrasound, and mammography. All patients were diagnosed with invasive breast cancer for the first time by core needle biopsy. If prompted, the patient underwent a hollow needle biopsy of the axillary lymph nodes under ultrasound to determine lymph node metastasis. Prior to starting the NAC, all 139 famale patients had undergone CT scan, including the head, chest, abdomen, pelvis, and bone, and single-photon emission computed tomography (SPECT) to ensure that there was no distant metastasis. The patients had not received any special treatment, including traditional Chinese medicine, hormonal treatment, radiotherapy, surgery, or other chemotherapy regimens. The individual patient characteristics are shown in Table 1. The staging of the tumor was performed accord- ing to the international tumor TNM staging system. Written informed and chemotherapy consent were obtained prior to the study. This study was conducted with the approval of the tumor hospital affiliated with Guangxi Medical University, which conforms to the ethical standards of Helsinki’s 1964 declaration and its later revision.
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