Study design in the evaluation of breast cancer imaging technologies

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).     

乳腺癌前哨淋巴结探查的研究进展

乳腺癌前哨淋巴结(sentinel lymph node, SLN)是乳腺癌淋巴转移通道中最先经历的第一级淋巴结。通过乳腺癌SLN预测乳腺癌区域淋巴结转移状况,为乳腺癌的准确分期和外科手术提供了重要的依据。根据示踪剂的不同,有两种方法可以探查乳腺癌SLN,其中使用放射性核素标记物作为示踪剂探查乳腺癌SLN是目前较具优势的方法,且不同于传统的淋巴显像;乳腺癌SLN探查的成功率受到诸多因素的影响,其探查技术亦需进一步的研究来提高。     

Differentiation of mammographically suspicious lesions: evaluation of breast ultrasound, MRI mammography and electrical impedance scanning as adjunctive technologies in breast cancer detection

AIM: Various modalities are used as an adjunct to mammography for differentiation of potentially suspicious breast lesions. Electrical impedance scanning (EIS) is a new technique based upon the principle that cancer cells exhibit altered local dielectric properties and thus show measurably higher conductivity values. The accuracy of differentiation of benign and malignant breast lesions was evaluated to determine whether EIS duplicates or supplements the results obtainable from ultrasound (US) or magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred mammographically suspicious lesions were examined using US, MRI and EIS. Definitive histology was acquired through either lesion biopsy or surgical excision. RESULTS: Fifty of 62 malignant lesions were correctly identified using EIS (81% overall sensitivity), 24/38 benign lesions were correctly identified as benign (63% specificity). Negative predictive value and positive predictive value of 67 and 78% were observed, respectively. kappa-factor evaluation revealed a value of 0.82 between MRI and EIS and 0.62 between US and EIS. CONCLUSIONS: EIS may be a valuable adjunct for differentiation of suspicious mammographic lesions. Based upon the calculated kappa-factor, EIS results supplement US examinations. Artifacts (superficial skin lesions, poor contact, air bubbles) currently result in the high false-positive rate of EIS.     

Improved breast cancer detection of prone breast fluorodeoxyglucose-PET in 118 patients

OBJECTIVE: To prospectively evaluate the breast cancer detection of prone breast positron emission tomography (PET) images in comparison with supine whole-body PET images. MATERIAL AND METHODS: One hundred and eighteen female patients (age range 28-91 years) with 122 lesions suspected of having breast cancer underwent fluorine-18 fluorodeoxyglucose PET for preoperative staging. After the whole-body image was acquired, prone breast PET imaging was performed. The findings from both images were compared with the histopathologic results. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy were used to compare the diagnostic accuracy of prone breast PET images with that of whole-body PET images. RESULTS: Sensitivity, specificity, positive predictive value, NPV, and accuracy of whole-body PET images were 83, 50, 97, 17, and 80%, and of prone breast PET images they were 95, 50, 96, 43, and 93%. Ten of 114 breast cancerous lesions (8.8%) were detected on prone breast PET images alone. Statistical difference was found between the sensitivity, accuracy, and NPV of prone breast PET images and those of whole-body PET images (P<0.0001 for sensitivity and accuracy and P<0.0009 for NPV). CONCLUSION: Our data about the 122 lesions, suspected of breast cancer, with regard to the usefulness of prone breast PET imaging indicate that prone breast PET images are effective in detecting breast cancer.     

The added benefit of digital breast tomosynthesis in second breast cancer detection among treated breast cancer patients

Objectives

We aimed to compare the recall rate (RR) and the cancer detection rate (CDR) of combined full field digital mammography and digital breast tomosynthesis (FFDM?+?DBT) to those of full field digital mammography (FFDM) alone in breast cancer survivors.

Microwave thermography in the detection of breast cancer

Microwave thermography, a method of sensing subcutaneous temperatures, was used in a breast cancer detection study of about 5,000 female patients. The data were taken at wavelengths of 9.1 and 23 cm. Microwave thermography at 23 cm has true-positive and true-negative detection rates of 0.8 and 0.6, respectively, comparable to those of infrared thermography (0.7) and inferior to those of xeromammography (0.9). However, a potential advantage results if microwave and infrared thermography are used together for screening, and if mammography is used only for follow-up on those patients who were positive on either the microwave or the infrared thermograms. It is then possible to obtain true-positive and true-negative detection rates of 0.9 and 0.9, respectively, while only half the number of patients need be subjected to x-rays.     

Light scanning versus mammography in breast cancer detection

Transillumination light scanning of the breast was compared with screen-film mammography in a prospective study of 1,110 women referred to an outpatient imaging department. Each method was interpreted independently of the other but with knowledge of physical examination findings. Of 24 biopsy-proved cancers, 14 (58%) were detected with light scanning and 21 (88%) with mammography. The 77 false-positive light scan examinations were attributed to technical factors and the inability of light scanning to distinguish malignant from benign conditions on the basis of imaging features. Of the ten false-negative light scan examinations, two were retrospectively reclassified as positive, but light scans in the other eight cases remained normal in appearance. The authors conclude that transillumination light scanning is not competitive with mammography as a screening method for breast cancer detection. furthermore, they were unable to identify a select subpopulation of women who might benefit from light scanning as an adjunct to mammography.     

MR lesion detection in a breast cancer population

Implementation of MR imaging of the breast as an extension of the existing imaging modalities in the diagnosis of breast cancer was evaluated in a university cancer center. MR imaging of the breast was performed in 54 patients, in whom the MR results were compared with the triple test (the combination of clinical examination, mammographic evaluation, and cytology) and the final histological diagnosis. MR imaging of the breast depicted 30 of the 33 malignancies (sensitivity, 91%). In two of the malignancies, the carcinoma was clinically and mammographically occult. For the three patients with a false-negative MRI diagnosis, the conventional mammography showed suspicious clustered microcalcifications as a sign of in situ carcinoma. For seven patients, MR imaging of the breast incorrectly suggested the presence of a malignant lesion (specificity, 67%). To improve MR specificity, we perform MR-guided ultrasonographic fine-needle aspiration biopsy (FNAB). Although MR imaging of the breast is a highly sensitive examination, conventional x-ray mammography remains the most efficient imaging modality in the diagnosis of breast cancer. In our patient population, MR imaging of the breast had additional value for women with mammographically dense breast tissue and especially for patients with clinical evidence of breast carcinoma that could not be detected with conventional diagnostic methods.     

Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

Objective The aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device. Methods Between January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal ¹⁸F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital. Results Of the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device. Conclusions In cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future.     

Emerging breast imaging modalities

Current limitations in mammography have impelled the development of alternative imaging modalities for general and/or high-risk screenings, problem-solving, diagnosis, staging, pre-surgical planning, and determination of treatment efficacy. From initial studies, emerging breast modalities may overcome the inherent weaknesses of current imaging procedures. Among the modalities discussed here are digital breast tomosynthesis (DBT), molecular breast imaging, automated breast ultrasound, breast elasticity ultrasound imaging, and cone beam breast CT (CBBCT).     

Impact of breast density on computer-aided detection for breast cancer

OBJECTIVE: Our aim was to determine whether breast density affects the performance of a computer-aided detection (CAD) system for the detection of breast cancer. MATERIALS AND METHODS: Nine hundred six sequential mammographically detected breast cancers and 147 normal screening mammograms from 18 facilities were classified by mammographic density. BI-RADS 1 and 2 density cases were classified as nondense breasts; BI-RADS 3 and 4 density cases were classified as dense breasts. Cancers were classified as either masses or microcalcifications. All mammograms from the cancer and normal cases were evaluated by the CAD system. The sensitivity and false-positive rates from CAD in dense and nondense breasts were evaluated and compared. RESULTS: Overall, 809 (89%) of 906 cancer cases were detected by CAD; 455/505 (90%) cancers in nondense breasts and 354/401 (88%) cancers in dense breasts were detected. CAD sensitivity was not affected by breast density (p=0.38). Across both breast density categories, 280/296 (95%) microcalcification cases and 529/610 (87%) mass cases were detected. One hundred fourteen (93%) of the 122 microcalcifications in nondense breasts and 166 (95%) of 174 microcalcifications in dense breasts were detected, showing that CAD sensitivity to microcalcifications is not dependent on breast density (p=0.46). Three hundred forty-one (89%) of 383 masses in nondense breasts, and 188 (83%) of 227 masses in dense breasts were detected-that is, CAD sensitivity to masses is affected by breast density (p=0.03). There were more false-positive marks on dense versus nondense mammograms (p=0.04). CONCLUSION: Breast density does not impact overall CAD detection of breast cancer. There is no statistically significant difference in breast cancer detection in dense and nondense breasts. However, the detection of breast cancer manifesting as masses is impacted by breast density. The false-positive rate is lower in nondense versus dense breasts. CAD may be particularly advantageous in patients with dense breasts, in which mammography is most challenging.     

Effective breast cancer detection with film-screen mammography

Non-visualization of the retromammary space and ribs has been a source of concern to mammographers. In six years, 186 cancers were detected in our experience of 10 034 self-referred asymptomatic women at the University of Michigan Breast Cancer Detection Demonstration Project. These cancers were used to analyze the need to visualize the retromammary space and ribs, or both sites, if adequate technical factors were used. All the cancers were analyzed for position on the film, number of films required for visualization, relationship of the tumor to the posterior edge of the film, number of occult tumors, tumor size, histologic type, sensitivity of detection method and the number of interval cancers. Of the 186 cancers, 168 (90%) were detected on mammograms. All of the cancers were visualized on the mediolateral view; three were not visualized on the craniocaudal view. Six per cent of the cancers were within 1 cm of the posterior edge of the film; the remaining 94% were located more anteriorly in the breast. The imaged tumors were smaller and had a significantly higher percentage of non-invasive cancers than found in a symptomatic clinical population. Therefore, mammography, using proper technique, will consistently permit visualization of cancer in the breast, regardless of tumor size, histologic type, or location in the breast.     

Ipsilateral-mammogram computer-aided detection of breast cancer.

In this paper, an ipsilateral multi-view computer-aided detection (CAD) scheme is presented for mass detection in digital mammograms by exploiting correlative information of suspicious lesions between mammograms of the same breast. After nonlinear tree-structured filtering for image noise suppression, two wavelet-based methods, directional wavelet transform and tree-structured wavelet transform for image enhancement, and adaptive fuzzy C-means algorithm for segmentation are employed on each mammograms of the same breast, respectively, concurrent analysis is developed for iterative analysis of ipsilateral multi-view mammograms by inter-projective feature matching analysis. A supervised artificial neural network is developed as a classifier, in which the back-propagation algorithm combined with Kalman filtering is used as training algorithm, and free-response receiver operating characteristic analysis is used to test the performance of the developed unilateral CAD system. Performance comparison has been conducted between the final ipsilateral multi-view CAD system and our previously developed single-mammogram-based CAD system. The study results demonstrate the advantages of ipsilateral multi-view CAD method combined with concurrent analysis over current single-view CAD system on false positive reduction.     

Computer-aided detection and diagnosis of breast cancer

The limitations of radiologists when interpreting mammogram examinations provides a reasonable, if not compelling, basis for application of computer techniques that have the potential to improve diagnostic performance. Computer algorithms, at their present state of development, show great promise for clinical use. It can be expected that such use will only improve as computer technology and computer methods continue to become more formidable. The eventual role of computers in mammographic detection and diagnosis has not been fully defined, but their effect on practice may one day be very significant.