冰冻切片与石蜡切片对乳腺肿瘤的诊断价值研究

目的:分析和比较冰冻切片与石蜡切片对乳腺肿瘤的诊断价值。方法:选取480例新鲜乳腺标本,将其制成冰冻切片以及石蜡切片,根据诊断结果进行对比分析,评价乳腺肿瘤的冰冻切片与石蜡切片的对乳腺肿瘤的诊断价值。结果:经石蜡切片诊断乳腺良性肿瘤277例,占57.71%,良性肿瘤中以乳腺纤维瘤诊断居多;经石蜡切片诊断乳腺恶性肿瘤203例,占42.29%,以乳腺浸润性导管癌居多。冰冻切片诊断乳腺良性肿瘤279例,占58.13%;恶性肿瘤195例,占40.62%;延迟诊断6例,占1.25%。以石蜡切片诊断结果为金标准,冰冻切片诊断乳腺良性肿瘤的准确率为98.56%(273/277),诊断恶性肿瘤的准确率为95.07%(193/203),假阳性率为0.72%(2/277),假阴性率为2.96%(6/203),冰冻切片与石蜡切片诊断乳腺肿瘤的结果具有显著一致性,K值为0.965(P0.05)。结论:冰冻切片与石蜡切片诊断乳腺肿瘤的符合率较高,可作为术中快速病理检测的手段,但该种切片方式存在少量延迟诊断,多与术者操作经验有关,故术中应注重制片过程,提高冰冻切片质量。     

Assessment of biomechanical parameters of the shoulder joint at the operated side versus non-operated side in patients treated surgically for breast cancer

Aim

Isokinetic assessment of biomechanical parameters of the shoulder joint at the operated side versus non-operated side in patients treated surgically for breast cancer according to the type of surgery performed.

早期乳腺癌保乳术后放射治疗的临床研究

目的:通过对早期乳腺癌保乳术后放射治疗的研究,探讨其远期疗效及瘤床加量照射和放化疗顺序等问题。方法:84例早期乳腺癌患者行保乳手术,术后行三维适形放疗,50Gy/25次,1次/天,5次/周,瘤床局部加量10～16Gy/5～8次。化疗采用蒽环类为主的方案,65例肿瘤直径>1cm者先化疗3个周期后放疗,然后再化疗1～3周期,13例肿瘤直径≤1cm者在术后3～6周放疗,然后化疗4～6个周期。ER/PR阳性者均行内分泌治疗。结果:全组病人5年生存率100%,5年无瘤生存率91.4%。3例乳腺局部复发,3例分别出现肺、肝和骨转移,其中2例死于肿瘤转移。总复发率7.1%。瘤床加量组局部复发率低于未加量组(P=0.04)。放化疗顺序对肿瘤复发率无影响(P=0.15)。美容效果优良率94%,一般者3.6%,差者2.4%。结论:放射治疗是早期乳腺癌保乳治疗的重要组成部分,瘤床加量照射可降低局部复发率。放化疗顺序对于局部复发率影响不大。     

Animal models for breast cancer

Rodent mammary tumors induced by chemical carcinogens have proven to be very useful in the genetic analysis of initiation, promotion and progression of mammary carcinogenesis. We are studying rat mammary carcinomas induced by the chemical carcinogen, N-nitroso-N-methylurea. The earliest genetic event observed in the mammary gland is the activation of Ha-ras oncogenes, which is followed by promotion of the initiated cells by hormones involved in puberty. Preferential amplification of the mutated Ha-ras allele, of PRAD-1 and IGF2, loss of expression of the mitogenic growth factor gene, MK, and mutation in the tumor suppressor gene, p53, are seen in the mammary tumors during tumor progression.     

Effects of radiation and chemotherapy on adipose stem cells: Implications for use in fat grafting in cancer patients

Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient’s ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved.     

A deep learning classifier for digital breast tomosynthesis

PurposeTo develop a computerized detection system for the automatic classification of the presence/absence of mass lesions in digital breast tomosynthesis (DBT) annotated exams, based on a deep convolutional neural network (DCNN).Materials and MethodsThree DCNN architectures working at image-level (DBT slice) were compared: two state-of-the-art pre-trained DCNN architectures (AlexNet and VGG19) customized through transfer learning, and one developed from scratch (DBT-DCNN). To evaluate these DCNN-based architectures we analysed their classification performance on two different datasets provided by two hospital radiology departments. DBT slice images were processed following normalization, background correction and data augmentation procedures. The accuracy, sensitivity, and area-under-the-curve (AUC) values were evaluated on both datasets, using receiver operating characteristic curves. A Grad-CAM technique was also implemented providing an indication of the lesion position in the DBT slice.Results Accuracy, sensitivity and AUC for the investigated DCNN are in-line with the best performance reported in the field. The DBT-DCNN network developed in this work showed an accuracy and a sensitivity of (90% ± 4%) and (96% ± 3%), respectively, with an AUC as good as 0.89 ± 0.04. A k-fold cross validation test (with k = 4) showed an accuracy of 94.0% ± 0.2%, and a F1-score test provided a value as good as 0.93 ± 0.03. Grad-CAM maps show high activation in correspondence of pixels within the tumour regions.Conclusions We developed a deep learning-based framework (DBT-DCNN) to classify DBT images from clinical exams. We investigated also a possible application of the Grad-CAM technique to identify the lesion position.     

Mouse models for breast cancer metastasis

Metastasis of cancer cells is the main cause of death in most breast cancer patients. Although markers for early diagnosis and drugs that limit the spread of cancer to other organs have been developed, it is difficult to prevent the relapse of breast cancer. Recent research has highlighted the importance of tumor environment in which communication between tumor cells and the body system occurs. Emerging data have suggested that animal models are a good system to investigate this communication. Therefore, studies with mouse models have been developed as a reasonable method for a systemic approach to understand breast cancer metastasis. In this review, we summarize mouse models of breast cancer and their applications to the study of human breast cancers, and discuss limitation of model system and advanced techniques to overcome it.     

Comparison among four immobilization devices for whole breast irradiation with Helical Tomotherapy

PurposeTo evaluate the repositioning accuracy of 4 immobilization devices (ID) used for whole breast Helical Tomotherapy treatments: arm float with VacFix® (Par Scientific, Denmark), all-in-one® (AIO®) system (Orfit, Belgium), MacroCast thermoplastic mask (Macromedics, The Netherlands) and BlueBag® system with Arm-Shuttle (Elekta, Sweden).Materials and methodsTwenty four women with breast cancer with PTV including the breast/chest wall and lymph nodes were involved in this study (6 women per group). Pretreatment registration results were first collected using automatic bone registration + manual adjustment on the vertebra followed by independent registrations on different ROIs representing each treated area (axillary, mammary chain, clavicular, breast/chest wall). The differences in translations and rotations between reference registration and the above mentionned ROIs were calculated. A total of 120 MVCT images were analyzed.ResultsSignificant differences were found between IDs (p < 0.0001), ROIs (p = 0.0002) and the session number (p < 0.0001) on the observed shifts, when examining 3D translation vectors. 3D-vectors were significantly lower for the BlueBag® than for the VacFix® or for the AIO® (p < 0.0001), but differences were not significant compared to the mask (p = 0.674). Finally, setup margins were overall smaller for the BlueBag® than for other IDs, with values ranging from 1.53 to 1.91 mm on the mammary chain area, 4.52–6.07 mm on the clavicular area, 2.71–4.62 mm on the axillary area, and 3.39–5.10 mm on the breast.ConclusionWe demonstrated in this study that the BlueBag® combined with arm shuttle is a robust solution for breast and nodes immobilization during HT treatments.     

A new split arc VMAT technique for lymph node positive breast cancer

PurposeTo investigate different volumetric modulated arc therapy (VMAT) field designs for lymph node positive breast cancer patients when compared to conventional static fields and standard VMAT designs.MethodsNineteen breast cancer patients with lymph node involvement (eleven left and eight right sided) were retrospectively analyzed with different arc designs. Proposed split arc designs with total rotations of 2 × 190° and 2 × 240° were compared to conventional field in field (FinF) and previously published non-split arc techniques with the same amount of total rotations.ResultsAll VMAT plans were superior in dose conformity, when compared to the FinF plans. Split arc design decreased significantly ipsilateral lung dose and heart V5Gy for both left and right sided cases, when compared to non-split VMAT designs. For left sided cases no significant differences were seen in contralateral lung mean dose or V5Gy between different VMAT designs. For right sided cases the contralateral lung dose V5Gy was significantly higher in split VMAT group, when compared to non-split VMAT designs. The contralateral breast dose V5Gy increased significantly for split VMAT plans for both sides, when compared to non-split VMAT designs or FinF plans.ConclusionsThe proposed split VMAT technique was shown to be superior to previously published non-split VMAT and conventional FinF techniques significantly reducing dose to the ipsilateral lung and heart. However, this came with the expense of an increase in the dose to the contralateral breast and for right-sided cases to the contralateral lung.     

Cone-beam breast computed tomography using ultra-fast image reconstruction with constrained,total-variation minimization for suppression of artifacts

Compressed sensing based iterative reconstruction algorithms for computed tomography such as adaptive steepest descent-projection on convex sets (ASD-POCS) are attractive due to their applicability in incomplete datasets such as sparse-view data and can reduce radiation dose to the patients while preserving image quality. Although IR algorithms reduce image noise compared to analytical Feldkamp-Davis-Kress (FDK) algorithm, they may generate artifacts, particularly along the periphery of the object. One popular solution is to use finer image-grid followed by down-sampling. This approach is computationally intensive but may be compensated by reducing the field of view. Our proposed solution is to replace the algebraic reconstruction technique within the original ASD-POCS by ordered subsets-simultaneous algebraic reconstruction technique (OS-SART) and with initialization using FDK image. We refer to this method as Fast, Iterative, TV-Regularized, Statistical reconstruction Technique (FIRST). In this study, we investigate FIRST for cone-beam dedicated breast CT with large image matrix. The signal-difference to noise ratio (SDNR), the difference of the mean value and the variance of adipose and fibroglandular tissues for both FDK and FIRST reconstructions were determined. With FDK serving as the reference, the root-mean-square error (RMSE), bias, and the full-width at half-maximum (FWHM) of microcalcifications in two orthogonal directions were also computed. Our results suggest that FIRST is competitive to the finer image-grid method with shorter reconstruction time. Images reconstructed using the FIRST do not exhibit artifacts and outperformed FDK in terms of image noise. This suggests the potential of this approach for radiation dose reduction in cone-beam breast CT.     

Aluminium in human breast tissue

Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.     

Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer: preliminary report

Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly in hormone-sensitive postmenopausal breast cancers. The initial results are reported. The patients were randomly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice daily (group A), exemestane 25 mg daily (group B) and letrozole 2.5 mg daily (group C). The analysis was based on 20 patients who received at least one cycle of treatment. Fourteen patients completed two cycles and 12 patients three cycles. All groups showed clinical response and there was decrease in tumor area in each group. However, complete clinical response was only observed for group A patients. There was also progressive decline in blood CEA and CA15.3 levels but the differences between the three groups were not significant. The results of the preliminary analysis are encouraging but definitive conclusion could only be drawn after the completion of the study.     

La pratique de l’IRM mammaire au centre hospitalier de Chambéry

ObjectiveTo determine indications, technique and results of breast MRI performed at Chambery hospital (CH).Patients and methodsAnalytical retrospective study of 12 months, conducted at CH. It involved the analyzing of 100 breast MRI examinations performed in 84 patients using a brand device Siemens Magneton Area^®.ResultsThe mean age of patients was 56.2 years. The indications for breast MRI were the assessment of local and regional extension of breast cancer (28%), the results of monitoring of neoadjuvant chemotherapy (22%), the research of local recurrence after conservative treatment (14%) and cases of diagnostic discrepancies (13%). The most commonly used sequences were axial T1 ES (91%), axial T2 STIR (91%) and axial T1 with gadolinium injection (97%). The assessment of locoregional extension revealed multifocal invasion in 14 cases, pectoral in 3 cases, lymph node in 7 cases and skin in 4 cases. Concerning the monitoring of neoadjuvant chemotherapy, tumor involution was found in 10 patients and stability in 3 others. The distinction between tumor recurrence and postoperative scar showed 10 negative cases and 4 cases of tumor recurrence.ConclusionBreast MRI is an excellent non-invasive method for studying fully and satisfactorily within. It is mainly practiced in the CH to the extension of cancer and monitoring neoadjuvant chemotherapy balance.     

三阴型乳腺癌的化学治疗和靶向治疗进展

三阴型乳腺癌(Triple negative Breast cancer,TNBC)占乳腺癌总数的15%,是一种免疫组织化学亚型。通常发生于青年女性,有很高的复发率,内脏和中枢神经系统转移早,病程短、死亡率高。对大多数TNBC患者,常规化疗是主要的治疗方式。20%患者有很好的化疗敏感性,对化疗耐药的TNBC患者靶向治疗为当前研究的热点,寻找乳腺癌新的治疗靶点,提出TNBC新的治疗策略,有望去改善TNBC患者的预后。     

血清多肿瘤标志物蛋白芯片检测在乳腺癌诊断中的价值

目的:探讨血清多肿瘤标志物蛋白芯片检测系统在乳腺癌诊断中的临床价值。方法:临床确诊的乳腺癌患者307例为乳腺癌组,非乳腺癌的其他恶性肿瘤患者495例为对照组。应用多肿瘤标志物蛋白芯片检测系统检测12种肿瘤标志物水平,评价血清肿瘤标志物的在乳腺癌组与对照组之间的差异。结果:CA153,CEA,Free-PSA这三项指标为诊断乳腺癌的独立相关因素(P<0.05),比较三项指标ROC曲线下面积可见,CA153对于鉴别乳腺癌准确性更高,其敏感性、特异性分别为78.92和56.14,女性乳腺癌患者Free-PSA可见明显升高,对乳腺癌有特殊提示意义,手术前后标志物CA199、CA242、Ferrin、CA125水平差异有统计学意义。结论:在临床常用的肿瘤标记物中,CA153,CEA,Free_PSA水平的升高与乳腺癌发生独立相关,其中CA153具有更高的诊断准确性,Free_PSA水平升高对乳腺癌的诊断有特别提示意义。     

Hypofractionated radiotherapy for early breast cancer: Review of phase III studies

Breast-conserving surgery including whole breast irradiation has long been a recommended procedure for early breast cancer. However, conventionally fractionated radiotherapy requires a lengthy hospitalisation or prolonged commuting to a hospital for radiotherapy. In recent years, hypofractionated radiotherapy has increasingly been used. This method involves higher fraction doses (above 2 Gy) as compared to conventional radiotherapy, so the total dose can be delivered in fewer fractions and in a shorter overall treatment time. This review aims at presenting most important outcomes of four randomised studies comparing conventional and hypofractionated radiotherapy schemes including a total of 7000 patients. These studies have not shown apparent differences in treatment efficacy, incidence of late post-radiotherapy complications or cosmetic effects during a 5–10 year follow-up, but longer observation is warranted to fully evaluate the safety of this method. Currently, major societies consider modestly hypofractionated radiotherapy schemes as a routine management in selected groups of patients undergoing breast-conserving surgery. However, this method should be used cautiously in patients with lymph node metastases, big breasts, receiving chemotherapy or trastuzumab, or those under 50 years of age.     

剪切波弹性成像对乳腺原位癌的诊断价值分析

目的:探讨剪切波弹性成像(SWE)对乳腺原位癌的诊断价值。方法:回顾性分析2015年8月-2017年8月于我院病理证实的26个乳腺原位癌病灶和45个乳腺良性病灶,术前均分别行常规超声检查和SWE检查。比较两组病灶的弹性模量值差异,两种检查方法诊断敏感度、特异度、准确度、阳性预测值、阴性预测值,并构建受试者操作特征(ROC)曲线,分析SWE对乳腺原位癌的诊断价值。结果:乳腺原位癌病灶的弹性模量最大值、平均值、最小值和与脂肪组织弹性比值分别为86.6±26.7 kpa、56.6±21.4kpa、31.3±15.7 kpa、6.7±1.8,均明显高于乳腺良性病灶(P0.05)。SWE诊断敏感度、特异度、准确度、阳性预测值、阴性预测值分别为92.31%、88.89%、90.14%、82.76%、95.23%,均显著高于常规超声成像(P0.05)。弹性模量最大值、平均值、最小值及与脂肪组织弹性比值评价乳腺原位癌的ROC曲线下面积分别为0.944、0.876、0.818、0.956。结论:乳腺原位癌病灶的弹性模量值高于良性病灶,SWE对早期发现乳腺原位癌具有重要价值。     

Ethiopian women's breast cancer self-examination practices and associated factors. A systematic review and meta-analysis

BackgroundBreast neoplasm is the most frequently diagnosed and the leading cause of cancer death in the vast majority of the countries. Breast cancer self-examination is a check-up of a woman does at home to look for changes or problems in the breast tissue. The benefit of early recognition is for early treatment that is more effective, higher long-term survival rates and better quality of life. The aim of this review was to determine the pooled prevalence of breast cancer self-examination practice and identify its associated factors among Ethiopian women.MethodsGoogle Scholar, PubMed, Science Direct, web of science, and Cochrane Library were used for search of articles. This review includes thirty four articles conducted in Ethiopia between 2011 and 2020. The review contains 14,908 women to determine the ever pooled prevalence of breast cancer self-examination practice. Health workers and students made up 28.35% of the total participants. Data were extracted using a standardized data extraction format prepared in Microsoft Excel and analyzed with Stata 14. To assess heterogeneity I² test were used. A random effect meta-analysis model was used to estimate the pooled breast cancer self-examination (BCSE) practice of Ethiopian women. Moreover associated factors were also assessed.ResultsIn Ethiopian women, the overall ever and regular pooled breast cancer self-examination practice was 36% (95% CI: 28, 43) and 16% (95% CI: 28, 43) respectively. The ever pooled prevalence for health workers or students was 53% (95% CI: 41, 65), whereas for other participants it was 25% (95% CI: 19, 30). Good knowledge about breast self-examination (AOR: 3.69: 95% CI: 2.70, 5.05), positive attitude towards BCSE (AOR: 2.72: 95% CI: 1.74, 4.24), Getting to know people with breast cancer(AOR: 2.77: 95% CI: 1.51, 5.09), family history of breast cancer (AOR: 2.49: 95% CI: 1.60, 3.88) and personal history of breast cancer (AOR: 2.26: 95% CI: 1.70, 3.01) were associated factors to BCSE practice among Ethiopian women. All of the studies included in this review were conducted in a cross-sectional design was a limitation of this review and meta-analysis.ConclusionThis review and meta-analysis showed the ever and regular pooled prevalence of BCSE among Ethiopian women. More than one third of Ethiopian women ever practiced BCSE. We recommend that awareness creation should be perform in order to tackle the risk of breast cancer.     

Emerging principles for the development of resistance to antihormonal therapy: implications for the clinical utility of fulvestrant

We seek to evaluate the clinical consequences of resistance to antihormonal therapy by studying analogous animal xenograft models. Two approaches were taken: (1) MCF-7 tumors were serially transplanted into selective estrogen receptor modulator (SERM)-treated immunocompromised mice to mimic 5 years of SERM treatment. The studies in vivo were designed to replicate the development of acquired resistance to SERMs over years of clinical exposure. (2) MCF-7 cells were cultured long-term under SERM-treated or estrogen withdrawn conditions (to mimic aromatase inhibitors), and then injected into mice to generate endocrine-resistant xenografts. These tumor models have allowed us to define Phase I and Phase II antihormonal resistance according to their responses to E₂ and fulvestrant. Phase I SERM-resistant tumors were growth stimulated in response to estradiol (E₂), but paradoxically, Phase II SERM and estrogen withdrawn-resistant tumors were growth inhibited by E₂. Fulvestrant did not support growth of Phases I and II SERM-resistant tumors, but did allow growth of Phase II estrogen withdrawn-resistant tumors. Importantly, fulvestrant plus E₂ in Phase II antihormone-resistant tumors reversed the E₂-induced inhibition and instead resulted in growth stimulation. These data have important clinical implications. Based on these and prior laboratory findings, we propose a clinical strategy for optimal third-line therapy: patients who have responded to and then failed at least two antihormonal treatments may respond favorably to short-term low-dose estrogen due to E₂-induced apoptosis, followed by treatment with fulvestrant plus an aromatase inhibitor to maintain low tumor burden and avoid a negative interaction between physiologic E₂ and fulvestrant.