Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.

Diagnostic Accuracy of Gray Scale Sonography for the Detection of Malignant Breast Tumour

Background: Gray scale sonography is an important diagnostic tool for the detection of malignant breast tumour. Objective: The purpose of the present study was to find out the diagnostic validity gray scale sonography to detect malignant lesions of breast. Methodology: This cross-sectional study was carried out in the department of Radiology and Imaging, in collaboration with the department of Surgery and Pathology at Banghabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from July 2008 to June 2009 for a period of one year. Women presented with clinically suspected breast mass from outpatients’ department (OPD) or inpatient department (IPD) were purposively selected and was Ultrasonographic diagnosis. 2-D Real-Time B-Mode Ultrasonographic examinations were done using high frequency (7.5 MHz) linear transducer. Result: Test of validity was done for color Doppler Sonographic findings in evaluation of benign and malignant breast lesion. Out of 50 cases, 23 cases were true positive;4 cases were false negative;1 case was false positive;22 cases were true negative confirmed by histopathology. Here sensitivity and specificity of Gray scale ultrasonography were 85.18% and 95.0% respectively. Here accuracy of Gray scale study was 90.0%. Positive predictive value was 95.83% and negative predictive value was 84.61%. Conclusion: Gray scale ultrasonography is a useful method in the differentiation between benign and malignant breast masses.

Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer

Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.

Advanced Papillary Carcinoma of the Breast Presenting as an Ulcerated Anterior Chest Wall Tumour: Case Report

BACKGROUND: Papillary carcinoma of the breast is a rare malignant tumour accounting for 1% - 2% of all breast cancers in women. Papillary carcinomas of the chest wall are always secondary to thyroid, thymus and ovaries. Other variants of breast cancer metastasizing to the chest wall have been reported. CASE: We report a 67-year-old woman presented to us with an ulcerated anterior chest wall mass of 1-year duration, bilateral axillary, supraclavicular and cervical swellings of 8-month duration. There was a history of breast lump which was noticed 5 years prior to presentation, no history of breast malignancy in the past and no family history of breast cancer. Examination revealed an ulcerated, nodular mass over the sternal angle which measured 14 cm × 12 cm × 4 cm;she had bilateral axillary, supraclavicular and cervical lymphadenopathy which were non-tender and matted. She had a firm, non-tender right breast lump measuring 6 cm × 4 cm. Chest examination and abdominal examinations were essentially normal. Chest X-ray revealed erosion of sternal bone without any evidence of intrathoracic extension. Abdominal ultrasound and thyroid scans were normal. Histology of the mass revealed papillary carcinoma. Biopsy of the right breast also revealed papillary carcinoma. She had excision of the fungating tumour and primary closure of defect. She subsequently had combination chemotherapy using ondasetron, cyclophosphamide, adriamycin and cisplantin. CONCLUSION: Papillary carcinoma of the breast is rare and rarely metastasizes to the chest wall. The diagnosis of metastatic chest wall tumour requires meticulous history taking, clinical examination and relevant investigations to ascertain the primary origin of the carcinoma.

Evaluation of Clinical and Radiological Tumour Response during Neo-Adjuvant Breast Cancer Chemotherapy at Yalgado Ouedraogo University Hospital

Background: Neoadjuvant chemotherapy (NAC) is one of the treatment options for breast cancer. Its aim is to significantly reduce the size of the tumour in preparation for surgery. The aim of this work is to analyze the conditions of clinical and radiological evaluation of NAC at the Yalgado Ouédraogo University Hospital (CHUYO). Patients and Methods: This was a descriptive cross-sectional study based on the medical records of patients followed up in the cancer department of the CHUYO from 1 January 2013 to 31 December 2021. All patients followed for histologically proven, non-metastatic breast cancer and having received at least one course of NAC were included in this study. The variables were related to the socio-demographic characteristics of the patients, the indications, the protocols of NAC and the sequences of evaluation of the tumour response (clinical, radiological and anatomopathological). Results: We collected 105 cases. The average age of the patients concerned was 44 years. The most frequent histological type was non-specific invasive carcinoma in 97.1% of cases. Immunohistochemically, triple-negative patients accounted for 51.4%. At the initial stage, all patients underwent clinical exploration. Clinical measurement of the tumour was performed in 70.5% of cases. The radiological size of the tumour was determined by ultrasound in 59.1% of cases. One patient had a breast MRI. Thirty-one patients were lost to follow-up after the initial evaluation. At mid-term and at the end of treatment, clinical tumour size was performed in 38.6% and 45.6% of cases respectively. There was no breast imaging performed at mid- and end-of-treatment. CT scans were performed in all cases at baseline, mid-term and end of treatment for extension assessment but did not mention the breast tumour. The tumour response rate was not recorded. Conclusion: Clinical assessment of tumour response is almost always empirical and not quantified. Medical imaging examinations are prescribed sparingly so as not to compromise the regularity of treatment and patient assessment.

Research Progress of Breast Cancer Stem Cell Stemness and Breast Cancer Recurrence

Currently, breast cancer is the most common malignant tumour in Chinese women with a high incidence rate, and recurrence and metastasis are the main reasons affecting survival. Breast Cancer Stem Cells (BCSCs) are stem cells capable of continuous regeneration in vivo with strong self-renewal ability and multidirectional differentiation potential, which are highly tumourigenic and insensitive to radiotherapy and chemotherapy, and are highly susceptible to breast cancer recurrence. Therefore, exploring the stemness of BCSCs and their mechanism associated with recurrence is important for developing new therapeutic strategies, improving therapeutic efficacy, and improving patient prognosis.

Serum Immunoglobulins (IgG, IgM and IgA) in Nigerian Women with Breast Cancer

Background: Breast cancer remains intractable and the leading cause of cancer related death among women. The appearance of breast tumour and its progression poses great clinical unpredictability before and after diagnosis, therapy and appearance of recurrent secondary deposits. Various immunological changes occur during breast tumourigenesis, and can be of value in the surveillance of the diseases. In our environment, there is scanty information on the value of these immunological factors especially immunoglobulins in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 59 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were prospectively recruited alongside with 20 patients with benign breast tumour representing patients’ control group and 20 apparently healthy age and sex-matched control subjects (mean age = 47.5 ± 13.4 yrs). Breast cancer patients were further grouped into early stage breast cancer (N = 25) and advanced stage breast cancer (N = 34). Patients were subjected to standard treatment modalities and pre- and post-treatment samples collected at intervals. Samples were assayed for IgG & IgM by immunoenzymatic methods and IgA by immunoturbidimetric method. Questionnaires and measurements were used to obtain necessary demographic and anthropologic information from the subjects. Results: Results showed that in all stages of breast cancer and treatment groups, the mean serum IgG, IgM and IgA levels respectively were not significantly raised (P > 0.05) when compared. Results also showed that majority (59%) of the patients presented at advanced stage of the disease. Low level of education and low income were among the prevailing risk factors. Majority (63%) of the cases had body mass index suggesting obesity (>30 kg/m2). Conclusion: Results suggest that serum immunoglobulin (IgG, IgM and IgA) levels are of limited value in surveillance of breast cancer in our environment. Based on our findings, it could also be concluded that low levels of education and low income are among the risk factors. Advocacy and evidence based policies aimed at prevention and early detection of the disease should be prioritized.

Pro-Inflammatory Cytokines (TNF-<i>α</i>and IL-1) in Nigerian Women with Breast Cancer

Background: Breast cancer remains an important medical challenge, despite sustained global efforts at its prevention and control. Various immunological factors are expressed in the serum during breast tumourigenesis, and can be of value in the surveillance of the disease. These serum bio-markers include pro-inflammatory cytokines since breast cancer is associated with chronic inflammation. In our locality with different racial/ethnic variations from Caucasian as well as environmental factors, there is scanty information on the value of these serum factors in screening and surveillance of breast cancer—hence the need for this study. Methodology: A total of 68 females (mean age = 48.7 ± 8.7 yrs) with clinically and pathologically confirmed breast cancer were recruited by self selection;representing breast cancer patients group. Due to small sample size they were further grouped into advanced stage breast cancer cases (N = 40) and early stage breast cancer cases (N = 28). Controls consisted of two groups: A—Patient control group (N = 21) comprised females with benign breast tumour (15 cases with fibroadenoma and 6 cases with fibrocystic disease) and group B—apparently healthy age/sex matched control group (N = 21). Pre-treatment samples were collected after which all patients underwent standard treatment modalities (neoadjuvant or adjuvant chemotherapy, radiotherapy, chemoradiation, and/or surgery;depending on the stage of presentation and thereafter post treatment samples were collected after 3 and 6 months respectively. Serum from the patients and controls were assayed immunoenzymatically for TNF-α and IL-1. Results: The results showed that at 6 months post-treatment stage, the mean values of IL-1 differed significantly (P > 0.05) when advanced stage breast cancer were compared with early stage and apparently healthy control groups respectively. Likewise at 6 months post-treatment stage, the TNF-α mean values differed significantly (P > 0.05) between advanced stage breast cancer and apparently healthy control. No significant differences in mean values were recorded across disease and treatment groups in both IL-1 and TNF-α at pre-treatment and 3 months post-treatment stages. Majority of the breast cancer patients studied were married (91%) and had children, of low income, never smoke cigarette, diagnosed at age above 46 years and presented at advanced stages of the disease. Results also showed that 78% of the cases did not have any history of cancer in their families. Also, 63% of the cases had body mass index values suggestive of obesity (>30 kg/m2). Conclusion: Results suggest that the use of serum levels of TNF-α and IL-1 in the diagnosis of breast cancer in our racial/ethnic environment is of limited clinical value. However it could be useful in disease surveillance in metastasis and relapse. Based on our findings, it could also be concluded that cigarette smoking and social sophistication are not among the risk factors to cancer in this part of the world, contrary to the situation in the advanced parts of the world.

乳腺弥漫大B细胞淋巴瘤临床特征及预后分析

目的:探讨乳腺弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征及预后。方法:回顾性分析2013年1月至2023年1月山西省肿瘤医院收治的28例乳腺DLBCL患者的临床资料,其中原发性乳腺DLBCL(PB-DLBCL)13例、继发性乳腺DLBCL(SB-DLBCL)15例对其临床表现、实验室检查、病理学检查、治疗方案和随访资料进行统计学分析。结果:PB-DLBCL患者与SB-DLBCL患者在IPI评分、LDH、β_(2)-微球蛋白方面比较,差异有统计学意义(P<0.05)。接受规律治疗的23例乳腺DLBCL患者中,13例初始治疗达到完全缓解(PB-DLBCL 9例,SB-DLBCL 4例),至随访截止日期,11例患者复发或进展(PB-DLBCL 5例,SB-DLBCL 6例),9例患者死亡(PB-DLBCL 3例SBDLBCL 6例)。PB-DLBCL组、SB-DLBCL组患者5年OS率分别为(75.0±15.3)%和(32.3±17.1)%,PFS率分别为(59.1±19.8)%和0,PB-DLBCL患者5年OS率及PFS率均高于SB-DLBCL患者(P<0.05);联合中枢预防治疗组5年OS率高于单纯化疗组(P<0.05)。结论:乳腺DLBCL分为PB-DLBCL和SB-DLBCL两大类,PB-DLBCL与SB-DLBCL相比,具有IPI评分、LDH水平、β_(2)-微球蛋白较低等特点,且PB-DLBCL患者生存期更长。此外,接受中枢预防治疗患者的预后更为乐观。

基于深度学习的乳腺肿瘤良恶性自动诊断

超声是目前诊断乳腺肿瘤的常用手段之一。针对超声中良恶性肿瘤纹理相似,区分度小等问题,论文提出了一个基于深度学习的乳腺超声良恶性自动诊断模型以辅助医生诊断。论文采用Densenet加强细节特征提取,注意力机制模拟临床诊断,迁移学习缓解数据依赖。实验结果表明,该模型可为年轻医生提供良好的辅助诊断,具有较好的可靠性和临床实用性。

藤黄酸在乳腺癌治疗中的研究进展

藤黄酸作为中药藤黄的主要生物活性成分,通过多种机制发挥抗肿瘤作用,包括诱导细胞凋亡、抑制肿瘤血管的生成和转移以及逆转肿瘤的多药耐药等;尤其是在乳腺癌治疗中可发挥多种抗肿瘤作用,有望成为乳腺癌的治疗药物。但藤黄酸自身存在缺陷,如水溶性差、半衰期短等,限制其临床应用。随着纳米载药制剂的不断发展,有望改善藤黄酸的不足,发挥藤黄酸强大的抗肿瘤作用。因此,综述近五年藤黄酸治疗乳腺癌的相关文献,以期为最大化藤黄酸抗乳腺癌奠定基础。

LAVA动态增强序列在乳腺磁共振检查中的应用价值

目的探讨三维容积超快速多期动态(LAVA)增强扫描序列在乳腺磁共振检查中的应用价值。方法38例临床疑似或钼靶提示为乳腺肿瘤的病人行MRI平扫及动态增强扫描,其中18例采用LAVA动态增强扫描序列,其余20例采用FAME动态增强扫描序列,对比分析两种动态增强扫描序列的图像质量及其对病灶的显示,并采用4分法评分。结果4分法原则评分,LAVA组:4分13例(72.2%),3分4例(22.2%),2分1例(5.6%),无1分病例;FAME组:4分3例(15%),3分11例(55%)2分5例(25%),1分1例(5%)。肿瘤血管显示情况。LAVA组:肿瘤供血动脉的来源动脉分支、异常增粗段及引流静脉清晰显示且走行连续,管径小于2 mm的血管得以显示;FAME组:肿瘤供血动脉异常增粗段及引流静脉显示,管径小于2 mm的血管显示困难,且走行连续性较差。结论LAVA动态增强序列图像质量优于FAME序列,能更清楚地显示乳腺肿瘤的形态、边缘、内部强化特点及其供血血管。

乐铂单药治疗乳腺癌的Ⅱ期临床研究

为了观察和评价乐铂单药治疗恶性肿瘤的疗效和毒副反应，１９９４年６月至１９９６年１０月，应用单药乐铂治疗复发性或转移性的乳腺癌病人４２例，乐铂５０ｍｇ／ｍ２，静脉滴注，每３周１个疗程，平均治疗２个疗程。结果，ＣＲ１例，ＰＲ１８例，有效率４５．２％。乐铂的毒性反应主要为骨髓毒性，特别是血小板减少，Ⅲ～Ⅳ级占１４．５％，为其剂量限制性毒性；其它常见的不良反应为胃肠道反应（Ⅰ～Ⅱ级）；乐铂的肾毒性和神经毒性不明显。

超声引导下麦默通治疗乳腺良性肿瘤的护理

目的探讨超声引导下麦默通治疗乳腺良性肿瘤的护理方法。方法重点对进行超声引导下麦默通治疗乳腺良性肿瘤的125例患者实施心理护理,做好各种术前准备,术中仔细观察病情变化及医护密切配合,术后加强观察和护理,积极预防可能出现的并发症。结果患者心理状况稳定,无严重并发症发生,手术效果满意。结论术前做好心理护理及各种准备,术中密切配合,术后加强观察和护理,不仅增加了手术成功率,而且有利于患者康复,还可以减少并发症的发生。

乳腺肿瘤C－erbB－2表达及预后意义的研究

应用免疫组化方法、观察了１０１例乳腺肿瘤Ｃ－ｅｒｂＢ－２癌基因的表达状况，１３例良性病变全部阴性，８８例乳腺癌中，阳性者４８例（５４．５％），阴性者４０例（４５．５％），两者间差异非常显著（Ｐ＜０．０１）。还发现Ｃ－ｅｒｂＢ－２表达多见于浸润性导管癌（１８／３３例）、单纯癌（２２／３４例）及浸润性小叶癌（３／１０例）。Ｃ－ｅｒｂＢ－２在乳腺癌中的表达与肿瘤大小、分级无显著关系，而与淋巴结转移有关。５５例乳腺癌进行了随访，Ｃ－ｅｒｂＢ－２阳性者，其死亡率（６４．５％）显著高于阴性者（１６．７％）。表明Ｃ－ｅｒｂＢ－２表达和乳腺癌患者预后有关。

体检和钼靶X线与超声对151例乳腺肿块检查结果比较分析

目的:比较分析体检、钼靶X线与超声诊断乳腺肿块的价值、优势和不足之处。方法:对151例经手术或穿刺明确病理结果的乳腺肿块进行回顾性研究,比较体检、钼靶X线与超声三种检查方法的诊断符合情况。结果:在151例乳腺肿块中,囊肿48例,体检、X线与超声的诊断准确率分别为68.75%、72.92%和93.75%;纤维腺瘤有65例,三者的诊断准确率分别为69.23%、72.31%和95.38%;增生结节27例,三者的诊断准确率分别为48.15%、48.15%和55.56%;乳腺癌11例,三者的诊断准确率为分别72.73%、72.73%和81.82%。结论:体检、钼靶X线与超声是最常用的检查乳腺肿块的方法,在鉴别肿块性质时,三者各有优势和不足之处。但对于良性肿块的诊断,超声更敏感;对于不典型肿块和乳腺癌,主张三者结合综合考虑。

乳管镜乳腺导管冲洗液细胞学检查和Her2、P21和P53蛋白表达对乳腺导管肿瘤的诊断价值

目的评价乳管镜下收集乳腺导管冲洗液细胞学检查和乳腺导管冲洗液脱落细胞Her2、P21、P53蛋白表达对乳腺导管良恶性肿瘤的诊断意义。方法在乳管镜直视下对46例乳腺导管癌和58例乳腺导管内乳头状瘤患者的乳腺导管病变进行搔刮,收集冲洗液打点涂片。用巴氏法行细胞学检查,用免疫细胞化学染色法行乳腺导管冲洗液脱落细胞的Her2、P21和P53蛋白检测。用χ2检验和秩和检验进行统计学分析。结果乳头溢液涂片上皮细胞量少,细胞往往有变性改变,核浓缩,结构均质化;乳腺导管冲洗液涂片细胞量丰富,核染色深,细胞形态保持完整。乳头溢液涂片中有效细胞团明显少于乳腺导管冲洗液涂片中的有效细胞团(P<0.01)。58例导管内乳头状瘤中,乳头溢液涂片细胞学诊断为良性57例,可疑恶性1例;乳腺导管冲洗液涂片细胞学诊断为良性56例,可疑恶性2例;两者比较差异无显著性(P>0.05)。14例伴有乳头溢液的乳腺癌患者乳头溢液涂片细胞学诊断的准确性明显低于46例乳腺癌患者的乳腺导管冲洗液细胞学检查(P<0.05)。46例乳腺导管癌乳腺导管冲洗液脱落细胞的Her2、P21和P53蛋白阳性表达率明显高于47例乳腺导管内乳头状瘤患者(P<0.05)。结论在乳管镜下收集乳腺导管冲洗液细胞学涂片的有效细胞团明显多于乳头溢液细胞学涂片,乳腺导管冲洗液细胞学检查诊断乳腺癌的准确性明显提高。免疫细胞化学方法检测乳腺导管冲洗液脱落细胞的Her2、P21和P53蛋白可作为鉴别乳腺导管良恶性肿瘤的参考指标。

乳腺叶状肿瘤的形态学和免疫组织化学研究

目的观察乳腺叶状肿瘤（phyllodes tumours,PTs）的形态学和免疫组织化学特征,并探讨其诊断标准。方法对21例PTs进行组织学观察和免疫组化SP法检测,并选取5例乳腺纤维腺瘤和5例乳腺腺病标本作为对照组。使用一抗包括CK-pan、EMA、SMA、p53、S-100蛋白、CD117、CD34、CD99、bc l-2、ER、PR、K i-67、CD10。结果21例PTs大体上均表现为界限清楚的肿块,且呈分叶状。肿瘤由具有双层排列的上皮成分以及过度生长的间质成分组成。根据间质的过度生长程度、细胞的异型程度、核分裂数、肿瘤边缘情况、有无异源性成分以及肿瘤性坏死等继发性改变将其分为良性、交界性和恶性3个级别。间质细胞免疫组化表达情况：CKpan：0/21、EMA：0/21、SMA：17/21、CD117：6/21、CD34：18/21、S-100蛋白：2/21、CD99：13/21、CD10：8/21、PR：5/21、ER：4/21、p53：18/21、K i-67：3%~10%、bc l-2：15/21。结论PTs的诊断主要依据组织学观察,免疫组化CD117、CD34、CD99、CD10、bc l-2的检测可以起到一定的辅助作用。

改进的随机森林算法在乳腺肿瘤诊断中的应用

为了解决乳腺肿瘤诊断中误差代价敏感的不平衡分类问题,提出一种改进的随机森林算法的乳腺肿瘤诊断模型。首先,在随机森林算法的基础上,将良恶乳腺肿瘤样本的诊断性能分开考虑,利用随机森林的泛化误差上界相关因素推导出ROC曲线的查全率(TPR)和误警率(FPR)的上界值。给出针对特定类别优化分类性能的基准,绘制出不同决策阈值下的TPR和FPR值的ROC曲线,调整平均关联度,再次训练,依据ROC曲线性能,确定最优平均关联度的诊断模型。最后,将该改进的随机森林算法与传统方法的诊断性能进行对比。实验结果证明,提出的方法模型在保证整体的诊断性能的前提下,对于提高恶性肿瘤的识别能力具有可行性和有效性。

表阿霉素、多西紫杉醇、5-氟脲嘧啶序贯对乳腺癌细胞凋亡的影响

目的:探讨表阿霉素(epirubicin,Epi)、多西紫杉醇(taxotere,Tax)和5-氟脲嘧啶(5-Fluorou-racil,5-Fu)序贯对乳腺癌细胞(MCF-7)凋亡的影响,为确定最有效的化疗方案提供理论依据。方法:采用硫基碱性蕊香红B(sulphorhodamine B,SRB)法分析3种药物序贯对MCF-7的细胞毒作用,中效原则分析药物之间的相互作用,流式细胞仪检测细胞周期和凋亡,Western-blot分析p53、bcl-2、bax和p21凋亡相关基因蛋白表达。结果:单一5-Fu产生较低细胞毒作用。序贯应用Epi、Tax有协同作用和增加5-Fu的细胞毒效果。序贯应用Epi、Tax导致细胞停滞于G1-M期,而5-Fu可加快细胞周期或杀死肿瘤细胞,且可使胸腺嘧啶合成酶(TS)表达减少。Epi、Tax和5-Fu序贯应用协同作用更明显(CI<1),同时诱导的MCF-7凋亡与雌激素受体(ER)、p53、bcl-2、bax状态无关。结论:Epi、Tax和5-Fu序贯应用可产生高度协同和时间依赖,实验结果对临床制定最有效化疗方案有重要作用。