Ovarian cancer screening: a look at the evidence

In 2005, more than 22,000 American women were diagnosed with ovarian cancer and 16,000 women died from the disease. The five-year relative survival rate for stage III and IV disease is 31%, and the five-year relative survival rate for stage I is 95%. Early diagnosis should lower the fatality rate. Unfortunately, early diagnosis is difficult because of the physically inaccessible location of the ovaries, the lack of specific symptoms in early disease, and the limited understanding of ovarian oncogenesis. Screening tests for ovarian cancer need high sensitivity and specificity to be useful because of the low prevalence of undiagnosed ovarian cancer. Because currently available screening tests do not achieve high levels of sensitivity and specificity, screening is not recommended for the general population. The theoretical advantage of screening is much higher for women at high risk (such as those with a strong family history of ovarian cancer and those with BRCA 1 or BRCA 2 mutations). However, even for women at high risk, no prospective studies have shown benefits of screening. The public health challenge is that 90% of ovarian cancer occurs in women who are not in an identifiable high-risk group, and most women are diagnosed with advanced-stage disease. Currently available tests (CA-125, transvaginal ultrasound, or a combination of both) lack the sensitivity and specificity to be useful in screening the general population. Ongoing clinical trials are assessing whether new tumor markers, including those generated by proteomic and genomic studies, will prove useful.     

Serum tumor markers

Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.     

Serum tumor markers in breast cancer: are they of clinical value?

BACKGROUND: Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. METHODS: The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. RESULTS: Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CONCLUSIONS: CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.     

A role for biomarkers in the screening and diagnosis of breast cancer in younger women

The widespread usage of screening mammography has resulted in an increase in the detection of early-stage disease, particularly in situ (stage 0) and early-stage (stage 1) cancers. However, incidence of stage 2 and 3 disease has not fallen commensurately, suggesting a bias in the detection of indolent cancers rather than aggressive cancers. Improved screening and diagnosis of a broader range of cancers is therefore an important need. Although MRI is a very sensitive breast cancer detection tool that has become standard for women at very high risk, it lacks sufficient specificity and cost-effectiveness for use as a general screen. The greatest opportunity for molecular tools to improve breast cancer outcomes is to better discern biologically aggressive cancers, especially in women under the age of 50 years. In this age group, presentation in stage 2 or 3 is more common and mammographic screening is less efficacious. We propose a multi-tiered triage strategy that uses emerging markers of susceptibility to segment the population for more focused screening with imaging. In particular, it would be helpful to identify a subset of at-risk, younger women who would benefit from intensive surveillance or preventive interventions. It is likely that tests for susceptibility, unless they are highly specific, will need to be combined with indicators of short-term risk. Although the combined sensitivity and specificity of screening must be high, each individual test does not require high specificity. It is important, however, for the susceptibility tests and short-term risk markers to be highly sensitive. If the majority of women under 50 years of age who develop breast cancer are captured with this strategy, then mammography screening for the general population can start at age 50 years. Finally, and perhaps most importantly, biomarkers of susceptibility and short-term risk are likely to provide insight into the biology of tumors that develop, leading to new interventions to support prevention. The most effective preventive strategies will be those where a marker predicts risk for the disease, as well as the benefit from preventive interventions.     

ABVS与MRI诊断乳腺肿块的临床价值比较

目的:比较自动乳腺全容积扫描(ABVS)与增强磁共振成像(MRI)诊断乳腺肿块的价值。方法:选取2018年1月-2019年6月本院收治的120例(164个病灶)乳腺肿块患者,均采用ABVS与MRI进行检查。比较两种方法诊断乳腺肿块的价值。结果:164个病灶中乳腺癌74个,良性肿块90个。ABVS汇聚征诊断乳腺癌的灵敏度为68.92%、特异度为83.33%、准确度为76.83%。ABVS正确诊断出了68个乳腺癌,漏诊6个、误诊9个。增强MRI正确诊断出了70个乳腺癌,漏诊4个、误诊5个。ABVS联合增强MRI正确诊断出了71个乳腺癌,漏诊3个、误诊3个。ABVS、增强MRI和二者联合诊断乳腺癌的灵敏度比较无统计学差异(P>0.05);二者联合诊断乳腺癌的特异度明显高于ABVS,差异有统计学意义(P<0.05)。结论:ABVS和增强MRI对乳腺肿块的诊断价值均较高,二者联合可提高对乳腺肿块的诊断特异性。     

Biochemical markers in breast cancer: which ones are clinically useful?

Breast cancer is the most common neoplasm affecting women in the Western world with approximately 1 in 11 developing the malignancy and 1 in 30 dying from the disease. For optimum management of these patients, assay of certain biochemical markers is necessary. Clinically, the most useful markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. Both American and European Expert Panels have recommended routine determination of these steroid hormone receptors in all patients with breast cancer. For surveillance of patients with diagnosed breast cancer, both CA 15-3 and BR 27.29 can be used. Serial determinations of these markers have the potential to preclinically detect recurrent disease and monitor the treatment of advanced disease. However, the benefit of this monitoring on patient outcome or quality of life is not clear. New or potentially new markers for breast cancer include BRCA1 and BRCA2 for selecting patients at high risk of developing breast cancer, urokinase plasminogen activator and PA1-1 for assessing prognosis and HER-2 for predicting response to the therapeutic antibody, Herceptin.     

Breast cancer diagnosis and screening

Approximately 180,000 new cases of breast cancer are diagnosed annually, accounting for about 48,000 deaths per year in the United States. The screening guidelines for the diagnosis of breast cancer are continually changing. Because of increased awareness of the signs and symptoms of breast cancer and the use of screening mammograms, breast cancers are increasingly being diagnosed at earlier stages. Annual mammograms and clinical breast examinations are recommended for women older than 40 years. Women older than 20 years should be encouraged to do monthly breast self-examinations, and women between 20 and 39 years of age should have a clinical breast examination every three years. These guidelines are modified for women with risk factors, particularly those with a strong family history of breast cancer. Ultrasonographic studies are most useful to evaluate cystic breast masses. For solid masses, diagnostic biopsy techniques include fine-needle aspiration, core biopsy and excisional biopsy.     

CEUS诊断乳腺癌研究进展

CEUS是纯血池显像,利用血液中含气微泡造影剂在声场中的非线性效应和强烈的背向散射获得对比增强图像,可动态直观地显示肿瘤微血管,已广泛应用于乳腺癌的诊断和疗效评估。CEUS在检出早期乳腺癌和识别前哨淋巴结方面具有较高敏感度和特异度,在评估新辅助化疗疗效、预测乳腺癌分子分型和辅助乳腺癌靶向治疗领域具有广阔的应用前景。本文对乳腺癌CEUS特点及其与生物标志物的关系、CEUS评价新辅助化疗疗效及辅助前哨淋巴结活检术方面的进展进行综述。     

Automated localization of breast cancer in DCE-MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly being used for the detection and diagnosis of breast cancer. Compared to mammography, DCE-MRI provides higher sensitivity, however its specificity is variable. Moreover, DCE-MRI data analysis is time consuming and depends on reader expertise. The aim of this work is to propose a novel automated breast cancer localization system for DCE-MRI. Such a system can be used to support radiologists in DCE-MRI analysis by marking suspicious areas. The proposed method initially corrects for motion artifacts and segments the breast. Subsequently, blob and relative enhancement voxel features are used to locate lesion candidates. Finally, a malignancy score for each lesion candidate is obtained using region-based morphological and kinetic features computed on the segmented lesion candidate. We performed experiments to compare the use of different classifiers in the region classification stage and to study the effect of motion correction in the presented system. The performance of the algorithm was assessed using free-response operating characteristic (FROC) analysis. For this purpose, a dataset of 209 DCE-MRI studies was collected. It is composed of 95 DCE-MRI studies with 105 breast cancers (55 mass-like and 50 non-mass-like malignant lesions) and 114 DCE-MRI studies from women participating in a screening program which were diagnosed to be normal. At 4 false positives per normal case, 89% of the breast cancers (91% and 86% for mass-like and non-mass-like malignant lesions, respectively) were correctly detected.     

Raman spectroscopy of breast tissues

Breast cancer is one of the leading female cancers. The major drawback of the gold standard of screening, mammography, is the high rate of false reports, aside from the risk from repeated exposure to harmful ionizing radiations. Histopathology, the gold standard of diagnosis, is time consuming and often prone to subjective interpretations. Molecular level diagnosis 'omics' is becoming increasingly popular; among these is metabolomics, diagnosis based on 'metabolic fingerprinting'. In the present article we review a Raman spectroscopic approach to metabolic fingerprinting in breast cancer detection. This review opens with a brief background on anatomical and etiological aspects of breast cancers. We present an overview of conventional detection approaches in breast cancer screening and diagnosis methods, followed by a concise note on the basics of optical spectroscopy and its applications in the screening/diagnosis of breast malignancy. We present the recent developments in Raman spectroscopic diagnosis of breast cancers and also share our experience in Raman spectroscopic classification of normal, benign and malignant breast tissues. Perspectives and current status of Raman spectroscopic screening/diagnosis of breast cancers are also discussed.     

MR成像在判断涎腺病变性质中的价值

目的确定MR成像是否可用于判断涎腺病变的性质,以及其诊断的准确性.方法对60例经手术病理证实的病例进行回顾性分析.将10个MR表现参数进行逻辑回归分析,确定哪些参数可预测涎腺病变的良、恶性.结果逻辑回归分析表明:在包括炎症病例的情况下,仅转移(P＜0.001)征象可预测病变的性质.而在不包括炎症病例条件下,颈部淋巴结肿大和周围结构侵蚀在预测涎腺恶性病变方面具有显著意义.用转移征象预测恶性病变的准确性为83.0%、敏感性为43.8%、特异性为100%;而侵蚀征象预测恶性病变的准确性84.9%、敏感性为50%、特异性为100%.当应用转移征象和/或侵蚀征象来预测恶性病变时,准确性为92.5%、敏感性为75%、特异性为100%.结论颈部淋巴结肿大和周围结构侵蚀在确定恶性涎腺病变方面具有较高的价值.     

The role of magnetic resonance imaging in screening women at high risk of breast cancer

Most women at very high risk of breast cancer because of a mutation in the genes BRCA1 or BRCA2, or a very strong family history of breast cancer, opt for intensive breast screening rather than bilateral prophylactic mastectomy. Annual screening mammography has low sensitivity in this population in part because of the greater breast density and faster tumor growth of younger women, resulting in cancers being detected at a suboptimal stage. In 11 prospective comparative studies, the addition of annual contrast-enhanced magnetic resonance imaging (MRI) of the breast to mammography demonstrated more than 90% sensitivity, more than twice that of mammography alone. False-positive rates were higher with the addition of MRI, but specificity improved on successive rounds of screening. Although survival data are not yet available, the stage distribution of these tumors predicts a significant reduction in breast cancer mortality rate compared with that of screening without MRI. Accordingly, annual MRI plus mammography is now the standard of care for screening women aged 30 years or older who are known or likely to have inherited a strong predisposition to breast cancer (based on the above evidence) and for women who received radiation therapy to the chest before the age of 30 years (based on expert opinion). Further research is necessary to define the optimal screening schedule for different subgroups. Formal studies of other high-risk populations (eg, biopsy showing lobular neoplasia or atypical ductal hyperplasia, dense breasts, and personal history of breast cancer at a young age) should be done before MRI screening is routinely adopted for these women.     

Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers worldwide. Its main application is mostly in gastrointestinal cancers, especially in colorectal malignancy. Although in use for almost 30 years, the clinical value of CEA in colorectal cancer is still not clear. METHODS: The literature relevant to the clinical value of CEA in colorectal cancer was reviewed. Particular attention was paid to studies involving metaanalyses and guidelines issued by Expert Panels. RESULTS: Although of little use in detecting early colorectal cancer, high preoperative concentrations of CEA correlate with adverse prognosis. Serial CEA measurements can detect recurrent colorectal cancer with a sensitivity of approximately 80%, a specificity of approximately 70%, and can provide a lead time of approximately 5 months. CEA is the most frequent indicator of recurrence in asymptomatic patients and currently is the most cost-effective test for the preclinical detection of resectable disease. CEA is most useful for the early detection of liver metastasis in patients with diagnosed colorectal cancer. Overall, however, little evidence is available that monitoring of all patients with diagnosed colorectal cancer leads to enhanced patient outcome or quality of life. CONCLUSIONS: Currently, the most useful application of CEA is in the detection of liver metastasis from colorectal cancers. Because of the relative success of surgery in resecting hepatic metastases, serial determinations of the marker are recommended for detecting cancer spread to the liver. In the future, preoperative concentrations of CEA may be included with the standard staging procedures for assessing prognosis.     

Does a better grade of tumour occurring in women under hormone replacement therapy compensate for their lower probability of detection by screening mammography

OBJECTIVE: To compare the prognostic factor of breast cancer survival between breast cancer diagnosed in subjects receiving hormone replacement therapy (HRT) before diagnosis to those without such a therapy. Subjects and methods: All breast cancers diagnosed between 1993 and 2000 within the breast cancer screening programme in Bouches du Rh?ne (France) were analysed for size, node status, and grade according to use, or not, of HRT. Univariate and multivariate analyses were carried out taking into account age, density of the breast, and mode of detection. RESULTS: The breast tumours diagnosed among HRT users had a lower grade whatever the mode of detection. The proportion of node positive tumours was identical in the two groups after adjustment for age. The smaller size of the tumours among HRT users is partly explained by the lower grade of these tumours Conclusion: Although tumours occurring in HRT users have a lower chance of being detected by screening, their prognostic factors, especially the grade of the tumour, are better than in non-users. More work is needed to find which part of this advantage is attributable to better surveillance of women treated with HRT     

血清糖类抗原199在健康人群中预测恶性肿瘤的意义

目的：评估血清糖类抗原199（CA199）在健康体检者中筛选胰腺癌以及其他恶性疾病的临床价值。方法选择6780例健康体检者,检测血清CA199,进行胸片、腹部超声、胃镜、结肠镜检查,分析CA199在检出胰腺癌与其他恶性肿瘤的灵敏度、特异度、阳性预测值。结果有585例患者（8.63％）的CA199≥37 U/ml。5例通过B超被诊断为胰腺癌,诊断出其他癌症的70个患者中的27位患者的CA199≥37 U/ml。 CA199正常值设定在≥37 U/ml,其诊断胰腺癌与其他恶性肿瘤的灵敏度为80.00％与32.86％,特异度为91.42％与91.62％,然而其阳性预测率仅为0.68％与3.93％。若CA199设定在＞80 U/ml,其诊断胰腺癌与其他恶性肿瘤的灵敏度为20.00％与10.00％,特异度为99.37％与99.43％,其阳性预测率为4.44％与15.55％。结论单纯依靠血清CA199作为体检人群恶性肿瘤的初筛工具不理想,需联合多种肿瘤标志物检测可以提高恶性肿瘤的诊断价值。在临床工作中,可以结合必要的影像学检查对血清CA199增高人群进行评估。     

Screening for gynecological malignancy.

Treatment for gynecological malignancy depends for its efficacy at least in part on the stage at presentation. Earlier diagnosis would allow the opportunity for more effective and potentially curative treatment. As a consequence, and in common with initiatives for many other cancers, a search for effective methods of screening is a high priority for the detection of early gynecological cancer. Such methods already exist for cervical cancer, and in many countries screening programs are in place to provide such early diagnosis. Patients with endometrial cancer often present symptomatically at stage I and as a consequence the value of screening of asymptomatic patients may be of lesser importance than for other cancers. Ovarian cancer, however, characteristically presents late and is insidious in onset and progress. Transvaginal ultrasound, together with serum tumor markers, may offer the possibility of early diagnosis and modification of therapy with the potential for improved outcome. However, the evidence from the literature is at present confusing, and it is worthwhile to review the current status of research data to evaluate the place of screening procedures for ovarian and other gynecological malignancies.     

Fine-needle aspiration biopsy of the thyroid nodule: uses and limitations

Thyroid nodules are a common occurrence in the general population, but only a small number of them are eventually diagnosed as cancers. Fine-needle aspiration biopsy (FNAB) is currently safe, the most accurate, and cost-effective method for the presurgical management of thyroid nodules, but there is a difficulty of the differential diagnosis between thyroid follicular adenomas and follicular carcinomas. The use of cellular markers may be useful in distinguishing follicular carcinoma from follicular adenomas. Several markers such as galectin 3 and HBME-1 initially appeared promising, but some discrepant results have been reported for these cellular markers. At the present time, assessing the likelihood of malignancy by examining various clinical parameters is an useful approach for follicular neoplasm.     

PET/CT检查在乳腺癌患者复发中的作用

目的研究乳腺癌患者血清肿瘤标志物出现异常后,PET/CT对早期发现乳腺癌复发的部位,及早进行治疗的价值。方法 82位乳癌患者,术后行常规复查时,出现1项或多项肿瘤标志物增高,常规行CT检查,检查后1-3个月内行PET/CT检查。当影像学检查提示阳性结节后,结果的最终判定是通过组织病理学诊断及随访。结果 PET/CT检查提示异常结节368个。真阳性：310个,假阳性：11个,真阴性：41个,假阴性：6个。在82名患者中,确诊为复发的真阳性患者：38名,假阳性：11名,真阴性：28名,假阴性：5名。结论乳腺癌患者血清肿瘤标志物异常后,PET/CT诊断复发的敏感性、特异性、准确性指标均高于CT。     

Comparison of breast mammography,sonography and physical examination for screening women at high risk of breast cancer in taiwan

Recommended surveillance for screening breast cancer, which includes regular mammography and clinical breast examination, has long been established in Western countries. This strategy may be too costly and unnecessary for countries with low incidences of breast cancer. The purpose of the present study is to compare breast mammography, sonography and physical examination in screening female relatives of breast cancer index cases from the hospital, and their relative efficiency. A total of 935 women over 35 years old, who were relatives of breast cancer patients, were invited to an annual screening by means of a combination of mammography, sonography and physical examination on a single day. A biopsy was performed when any of the three investigations indicated a possibility of malignancy. A total of 21 breast cancers, including sixteen invasive cancers and 5 noninvasive cancers, were detected among the 935 high-risk women. Of the cancers, 18, including 16 invasive cancers and 3 noninvasive cancers, were detected by sonography. In contrast, only 11 invasive cancers were detected by mammography, and 7 by physical examination. There were only 14 cancers detected by a combination of mammography and physical examination. The 7 (33.3%) additional cancers were detected when sonography was added. The sensitivity of sonography was 90.4%, which was higher than mammography (52.4%) and physical examination (33.3%), or even a combination of these two modalities (66.7%). This indicates that sonography is a more accurate screening tool for breast cancer in the high-risk group. Although breast sonography has not yet been recommended as a routine screening tool for breast cancer in Western countries, it may be superior to mammography and physical examination for the screening of Taiwanese high-risk female relatives of breast cancer index cases. If it should also be considered as a routine adjunct screening modality for Taiwanese women with lower rates of breast cancer will need further study.