Detection Of Occult Breast Cancer Research Articles

Effectiveness of mammogram and ultra-sonogram in the diagnosis of breast cancer in asymptomatic women at Central Karnataka

Background: Breast cancer is one of the most common cancers among women around the world. Some occult breast cancers can be missed when using ultrasound or mammogram alone. Considering this background, the study was performed to highlight the improved diagnostic efficacy of identifying breast cancer when using both ultrasound and mammogram as a combined modality.Methods: A total of 150 cases of suspected breast cancer were studied over a period of 2 years. Ultrasonography, and mammography were done by two independent radiologists and the results were analyzed. The patients were tested for BRCA1/2 gene mutations. Histopathology was done finally to confirm the diagnoses.Results: The 39 cases out of 150 asymptomatic women screened for breast cancer showed that they were positive for breast cancer by histopathology and 38 were positive by mammogram and ultra-sonogram. Cancer was prominently diagnosed in the age group of more than 40 years (92.3%) and 82.1% of women were in premenopausal stage. High BMI had a statistically significant correlation with breast cancer. The 71.7% of breast cancer cases were obese and 25.6% were overweight individuals. 89.7% of breast cancer cases were from the urban population. Detection of mutation in the BRCA gene showed 28 cases with a mutation in the BRCA-1 gene and 4 cases with a mutation in the BRCA-2 gene.Conclusions: The study confirms that mammography in addition to ultrasonography improves the sensitivity of detection of occult breast cancer in asymptomatic women.

How can additional ultrasonography screening improve the detection of occult breast cancer in women with dense breasts?

PurposeAlthough mammography is a gold standard for breast cancer screening, the number of cancers that cannot be detected with mammography is substantial, especially in dense-breast (DB) women. Breast sonography can be a useful and powerful screening tool in these cases. The aim of this study is to assess the application of whole-breast sonography in the evaluation of breast lesions in women with DB tissue and estimate its accuracy in comparison with mammography.Material and methodsA total of 207 asymptomatic DB women participated in this study. The breast tissue density was assessed using ACR BI-RADS. Patients underwent high-resolution ultrasonography of the breast in addition to physical examination and mammography. Different risk factors were also assessed.Results152 of 207 (73.4%) cases who had mammography performed had DB, and 55 (26.6%) cases had very dense breasts (very DBs). None of the cases had a positive history of malignancy, while 19% of them had a positive history of breast cancer in first- or second-degree relatives.ConclusionsAll findings were higher in cases with DB compared to very DBs except for fibroadenoma, which was detected more in cases with very DBs. Our study showed that the prevalence of different breast lesions had a significant relationship with the density of the breast. In our study, 48.3% of the cases were diagnosed with a lesion in their sonography result, although 81.0% of them were benign lesions, and the other 19.0% needed follow-up or biopsy evaluation. A substantial number of mammographically occult breast lesions, either benign or malignant, could be detected by ultrasound in DB tissue.

The Role of Ultrasound in Breast Cancer Screening: The Case for and Against Ultrasound

Mammography is the gold standard for breast cancer screening. However, with increasing awareness among patients and health care providers of mammography limitations especially in dense breasts, supplemental screening for breast cancer with ultrasound and magnetic resonance imaging has been expanding. The roles of both in screening need to be re-examined. This article reviews the efficacy, utility, and feasibility of ultrasound as a screening tool for the early detection of occult breast cancer.

Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

Gastric metastasis or carcinomatosis from primary breast cancer is a rare phenomenon. It is more prevalent in the invasive lobular type of breast cancer, although the most common histologic subtype of breast cancer is the invasive ductal type (1-4). To date, there are only a few case reports demonstrating that gastric metastases were manifested as an initial presentation of invasive lobular breast cancer (5-9). Nevertheless, most of the cases were distant recurrences occurring in patients with breast cancer histories (5-8). As of now, there is only one published case study reporting about gastric metastasis originating from occult breast lobular cancer and its focus was mainly on the distinct immunohistochemical features between primary gastric cancer and metastatic breast cancer (9). Therefore, in our report of a case of invasive lobular breast cancer identified by gastric metastasis, its imaging features, which significantly contributed to the detection of occult breast cancer, were described. CASE REPORT

Breast Cancer Screening and Problem Solving Using Mammography, Ultrasound, and Magnetic Resonance Imaging

Although mammography is the mainstay of early breast cancer detection, it has known limitations, particularly in women with dense breasts. As a result, additional imaging modalities, including ultrasound and contrast-enhanced magnetic resonance imaging, are also being used to supplement mammography in the early detection of occult breast cancer. This article reviews the indications and efficacy of mammography, ultrasound, and magnetic resonance imaging as both screening and diagnostic tools.

Molecular Detection of Micrometastatic Breast Cancer in Histopathology—Negative Axillary Lymph Nodes Fails to Predict Breast Cancer Recurrence: A Final Analysis of a Prospective Multi-Institutional Cohort Study

To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence. The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

WE‐C‐201C‐01: Perspective on the Developing Modalities for Breast Cancer Imaging

Perspective on the Developing Modalities for Breast Cancer Imaging Digital mammography has already become the new standard, replacing screen‐film for breast cancer screening, and for diagnostic work‐up of suspicious findings. New digital imaging technologies may use x‐ray beam characteristics such as tungsten target, silver filtration, and higher kVp; in ways that represent a departure from the long established screen‐film techniques. Representing a logical evolution from two‐dimensional to tomographic and 3D imaging of the breast, breast tomosynthesis and dedicated breast CT are currently investigated as potential replacements or adjuncts to mammography. Mammography (screen‐film or digital) is the single most effective tool for the detection of occult breast cancer with an overall sensitivity as high as about 85% for older women and about 60% or lower for women under the age of 50 years (Rosenberg RD et al. Radiology. 1998;209:511–8, Pisano E et al. N. Engl. J. Med. 2005;353: 1773–83). Attempts to increase sensitivity have included the use of intravenously injected (IV) contrast with digital mammography, tomosynthesis or breast CT but these efforts are in the research stage. With improved hardware and image acquisition techniques, the role of IV contrast injected MRI is gradually expanding as a diagnostic tool, and it is also recommended for screening of high risk patients, due to its high sensitivity. Ultrasound, a well established modality for diagnostic work‐up is evolving from the conventional pulse echo‐based approach to elasticity imaging and ultrasound CT of the breast. Breast scintigraphy with a dedicated camera is now in clinical use and it receives much attention as an adjunct to mammography. Other technologies that include diffuse optical tomography as a stand‐alone modality or in conjunction with MRI or with x‐ray imaging are currently under investigation. We are likely to see an increasing use of alternative imaging approaches in conjunction with mammography, ultrasound and MRI, the three essential modalities for breast cancer detection and for diagnostic work‐up of positive findings.Learning Objectives:1. Appreciate recent advances in the physics and engineering in x‐ray detector technology that contributed to the development of digital mammography, tomosynthesis and dedicated breast CT.2. Recognize the potential quantitative applications and important limitations of the x‐ray based breast imaging modalities.3. Appreciate recent technological developments in current clinical non‐x‐ray modalities such as MRI and ultrasound and their increasingly important role in breast cancer imaging.4. Gain perspective on some emerging modalities such as optical diffuse tomography and their potential role in the detection and diagnosis of breast cancer.

Design of optimal collimation for dedicated molecular breast imaging systems.

Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7-10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5-3.2, while maintaining a collimator resolution of either < or =5 or < or = 7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform

Comparison of infrared sentinel breastscan (SBS) and bilateral MRI for detection of occult breast cancer: Can this modality assist in surgical planning?

11553 Background: Sentinel BreastScan (Sentinel BreastScan, Infrared Sciences Corp. 2006) is a screening modality that uses digital infrared imaging (DII) and artificial intelligence to identify ph...

Lunx Is a Superior Molecular Marker for Detection of Non-Small Lung Cell Cancer in Peripheral Blood

The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.

Analysis of sensitivity and specificity of cytokeratin 19 reverse transcriptase/polymerase chain reaction for detection of occult breast cancer in bone marrow and leukapheresis products.

The work aimed to evaluate the sensitivity and specificity of the cytokeratin (CK) 19 reverse transcriptase/polymerase chain reaction (RT-PCR) for the detection of occult breast cancer in bone marrow and leukapheresis products. Peripheral blood and bone marrow samples, obtained from 96 and 8 healthy donors respectively, served as negative controls. A total of 115 bone marrow samples and 29 leukapheresis samples from routine patients with breast cancer were analysed by CK19 RT-PCR. The PCR results were compared with those from routine immunocytology for CK8, 18, 19. The CK19 RT-PCR technique with primer pairs from Datta et al. (J Clin Oncol 12: 475-482, 1994), using an annealing temperature of 72 degrees C, allowed the detection of one tumour cell in 10(7) mononuclear cells. None of the control samples (96 peripheral blood and 8 bone marrow) that were positive for beta2-microglobulin by RT-PCR showed a signal for CK19. However, expression of CK19 mRNA was observed in 40.87% (70/115) of bone marrow and in 24.13% (7/29) of leukapheresis samples of patients with breast cancer. Standard immunocytology and PCR were combined for the detection of tumour cells. Five of the 65 bone marrow samples were found to be positive by CK19 RT-PCR, but were negative with the immunocytology method. RT-PCR using CK19-specific primers and optimal experimental conditions is a reliable and specific method for the detection of micrometastatic breast cancer cells.

Modern breast ultrasound. Potential and limitations

The rapid development of sonography made it seem advisable to reconsider the clinical value of breast ultrasound. Our experience with new techniques and current research will be presented. Various indications for breast ultrasound will be discussed. New Doppler techniques extending the ability to detect low blood flow will be presented. The differentiation of suspicious areas seen on mammography and the detection of occult breast cancer are the major challenges in breast ultrasound. A limitation is its low capability to visualize microcalcifications. A promising approach is the development of highly sensitive, color-coded techniques for the detection of minimal blood flow. Another progress is the development of an ultrasound contrast medium that is not inactivated during first lung passage. Breast ultrasound provides complementary information to mammography. Using stable ultrasound contrast medium and highly sensitive color-coded Doppler techniques for the detection of minimal blood flow, we hope to find new criteria for the diagnosis of angioneogenesis in breast cancer.

Minimal illegitimate levels of cytokeratin K19 expression in mononucleated blood cells detected by a reverse transcription PCR method (RT-PCR)

Cytokeratin K19 ( CK19) expression was evaluated by a reverse transcription PCR method (RT-PCR) in the RNA obtained from peripheral blood stem cell collections (PBSC) from four patients with breast cancers (BC) and 34 mononucleated blood cell (MBC) negative controls (17 PBMC from normal subjects 12 PBSC from different types of leukaemias – M3, M4Eo, M2, etc. – and two from patients with Hodgkin's lymphoma; and three bone marrow (BM) collections). Two BC tissues were taken as positive controls. The method studied (Datta YH, Paul T, Adams PT, Drobyski WR. Sensitive detection of occult breast cancer by reverse transcription polymerase chain reaction. J Oncol 1994;12:475–8) is sensitive enough to allow the detection of CK19 transcripts in a 10 −6 dilution of cDNA reverse transcribed from 1 μg of BC RNA, but CK19 transcripts were also detected in 64% of the RNA obtained from the MBC controls. However, the amplified product detected in the control samples represents the transcript of the CK19 gene as confirmed by the results of Mae III digestion. It should be pointed out that although the CK19 expression was detected, the levels of expression in PBMC were almost negligible for they disappeared at 1:5 cDNA dilution. Moreover, a direct relationship between the number of BC cells added to PBMC and the increasing dilution levels of the cDNA necessary to prevent CK19 expression was observed. This allows us to conclude that the cDNA dilutions make it possible to distinguish the false from the true positive samples and that, in addition, the cDNA dilutions inform about the degree of BC cell contamination.

Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction.

Detection of occult carcinoma in patients with breast cancer may aid the establishment of prognosis and development of new therapeutic approaches. To improve on existing methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19) transcripts to identify mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. Peripheral-blood or bone marrow samples obtained from 34 patients with stages I to IV breast cancer and 39 control subjects without breast cancer were screened for K19 mRNA by nested primer PCR. In reconstitution experiments, K19 RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear (PBMN) cells. Four of 19 patients with stage IV breast cancer had detectable K19 transcript in peripheral blood. Five of six patients with histologically negative bone marrow biopsies following preablative chemotherapy and before autologous bone marrow transplant (BMT) were positive by this assay. Stem-cell apheresis harvests obtained from one of these patients and three additional patients immediately before BMT were all K19-negative. K19 RT-PCR analysis of CSF from a breast cancer patient with known carcinomatous meningitis was also positive. Thirty-eight of 39 non-breast cancer patients had negative K19 RT-PCR assays. The one exception was a patient with chronic myelogenous leukemia. RT-PCR of K19 is a sensitive, specific, and rapid method for detection of occult mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. The presence of residual breast cancer cells in histologically normal bone marrow aspirates but not in stem-cell apheresis harvests is a frequent finding. This assay may be useful in diagnosing metastatic disease, as well as in monitoring the effectiveness of systemic therapy.

Xeroradiographic detection of occult breast cancer.

Seventy-five occult cancers of the breast were found in a group of 7010 patients examined by xeroradiography, an incidence of 1% of all patients referred in a group practice setting. Nonpalpable cancers can be shown as a mass with or without calcifications, or as clustered calcifications only. A technique for preoperative localization of occult cancer is discussed. This, plus accurate marking of the surgical specimen, is important in the management of these cases.