New Diagnostic Techniques for Breast Cancer Detection

Mammography: Existing & New Developments

The beneficial effect on cause-specific survival of screening mammography in women aged 50-60 years has been shown in all studies that compared screening with no screening for breast cancer. A study of all such trials showed a reduction in mortality of 20-30%.^[1] For women in their 40s, 15-year mortality from breast cancer was reduced by 20%,^[2] even though mammographic screening has been shown it to be most effective after 55 years of age.^[3] Gotzsche and Olsen, in their meta-analysis, reviewed the methodological quality of mammography trials and challenged the efficacy of mammography in reducing mortality from breast cancer,^[4] although an independent review of the meta-analysis concluded that in women aged over 50 years, the benefit from screening mammography can not be negated.^[5]

The accuracy of conventional analog mammography is influenced by age and breast density, with sensitivity in dense breasts as low as 30-48%.^[6] Sensitivity increases from 69% at 40 years of age to 83% at 75 years.^[7] On average, 11% of women undergoing mammography screening need further diagnostic workup, of which 3% turn out to have a malignancy.^[8] False-positive mammography increases the anxiety of patients.^[9] Young age, dense breasts, use of estrogen-replacement therapy, family history of breast cancer and increased interval between mammography are some of the factors leading to false-positive mammography.^[10] A poorer sensitivity of mammography in young women with dense breasts can also lead to false-negative interpretations of the mammography.^[11] Thus, advances in conventional mammography may lead to improved early detection.

Full-field digital mammography (FFDM) utilizes digital detectors in place of the screen and film used in conventional mammography, giving more latitude and contrast resolution.^[12] Digital detectors absorb x-ray photons and convert them into electric charge, and with the help of analog-to-digital converters, the image is changed to digital value (Figure 1A & B).^[13]

(Enlarge Image)

Full-field digital mammograms. (A) Full-field digital mammogram showing benign calcifications. Note the clear visualization of skin, nipple and pectoral muscle, with good contrast detail within the glandular parenchyma. (B) Full-field digital mammogram windowing to show difference in dense breast (right axillary projection).

Full-field digital mammography optimizes image acquisition, storage and display, as well as allowing manipulation of image-contrast postprocessing. A multicenter FFDM trial showed sensitivity of 70% compared with 55% for conventional mammograms in women with dense breasts and aged under 50 years.^[14] The Digital Mammography Imaging Screening Trial (DMIST) was designed to measure small but potentially important clinical differences in diagnostic accuracy between digital and film mammogram. This was a multicentric trial, which recruited almost 50,000 women. All of the participants underwent both digital and film screening mammography in random order. In total, 85.8% had negative FFDM and mammography, 5.7% had positive mammography, 5.6% had positive FFDM and 2.9% had positive FFDM and mammography. The performance of digital mammography was no different than film-screen mammography as a whole, but was significantly better than film-screen mammography among women aged under 50 years (i.e., premenopausal, perimenopausal and women with dense breasts). FFDM also provided easier access to images and use of computer-aided detection (CAD), and easier storage and retrieval of images. The use of FFDM may be justified in the specific subgroup where it showed increased sensitivity. Fischmann conducted a study in 200 women to compare image quality and lesion detection for FFDM and conventional full-screen mammography.^[15] No improvement in detection of masses with FFDM was reported, but FFDM was advantageous owing to its contrast resolution in excluding masses and better classified parenchymal density. There was also better depiction of nipple, skin and pectoral muscle. The paper concluded that FFDM was equal or superior to conventional mammography for all image quality and detection parameters studied.

A prospective study carried out to compare FFDM with conventional mammography for detection and characterization of microcalcifications found that the image quality of FFDM was superior in over 50% of cases.^[1] In total, 40% of cases showed more calcifications in the FFDM arm, and FFDM had a sensitivity of 95.2% and specificity of 39.3% compared with 91.9 and 36.3% for conventional mammography.^[1] Higher diagnostic accuracy was shown in FFDM. Other advantages are constant image exposure at an optimal level and less need for repeat imaging, no film artifacts, and the ability to allow almost instant data transfer between centers. Although Lewin et al. found no significant difference in cancer detection between FFDM and conventional mammography in a screening population, FFDM did result in fewer recall rates.^[16] FFDM use is rapidly expanding in clinical settings and the outcome of this rapid uptake is currently being investigated in various studies.

Computer-aided detection programs recognize abnormal patterns in breast imaging and draw attention to masses, calcifications and parenchymal asymmetry on the digital breast image.^[17] CAD is helpful in reducing variability among radiologists.^[18] Various studies investigating CAD in screening mammography demonstrate its ability to detect mammographic signs of cancer and reduce the false-negative rate by 50-70%.^[19] In some studies, CAD missed findings,^[20] but there are also concerns that CAD may unduly increase recall rate and biopsy rates.^[21] Freer et al. prospectively assessed CAD in the interpretation of screening mammography in a community breast center.^[22] CAD resulted in a 19.5% increase in the number of malignancies detected and also improved detection of early breast cancer from 73 to 78%.^[22] It appears that CAD increases sensitivity but may lead to a fall in specificity; however, in this study the positive predictive value (PPV) for biopsy was not affected by CAD, and the radiologist and CAD were statistically equal in their ability to detect mammographic signs of malignancy.^[22] Another study, conducted to test radiologist performance with use of CAD in breast cancer diagnosis, found that the receiver operator curve increased from 0.61 without CAD to 0.75 with use of CAD. Use of CAD increased the sensitivity (from 73.5 to 87.4%) and specificity (from 31.6 to 41.9%) for detection of malignant breast lesions.^[23] Fenton et al. studied the association between use of CAD at mammography facilities and performance of screening mammography. They found that diagnostic specificity reduced from 90.2% before implementation of CAD to 87.2% after its introduction. The rate of breast biopsy increased by 19.7%, and an increase in sensitivity from 80.4 to 84.0% was not found to be statistically significant. This study concluded that use of CAD is associated with reduced accuracy of interpretation of screening mammography.^[24]

The current CAD system is not for independent use but may act as an adjunct to radiological interpretation. CAD can also be used with FFDM to improve interpretation of results.^[24] The most popular CAD system currently used is the R2 image checker, which marks potential breast masses, microcalcifications and lesions with high probability of malignancy.^[25]

As we have seen, mammography has limited sensitivity in dense breast, where superimposition artifacts can obscure lesions. However, new promising techniques to overcome this limitation are on the horizon. Use of contrast to enhance the imaging, and tomosynthesis - a cross-sectional technique - are being widely studied.

Contrast-enhanced Mammography. There are two basic techniques that use contrast in imaging breast: temporal-subtraction mammography and dual-energy mammography. For temporal-subtraction mammography, an unenhanced image is obtained, followed by a contrast-enhanced image.^[26,27] As in contrast-enhanced MRI, precontrast images are subtracted from postcontrast images for evaluation of enhancement. This technique is based on MRI protocols where malignant tumors show an atypical washout pattern, though it can not adopt the pattern obtained by MRI.^[28] The major drawback is the presence of motion artifacts and the higher radiation dose to patients.

Dual-energy mammography is another method of visualizing contrast in mammography systems. After giving intravenous contrast, two images of breast are obtained, one with a higher energy level, which absorbs more x-rays. The two images are then subtracted for optimal visualization of the contrast. This technique utilizes much more energy levels as compared with conventional imaging.^[29] For visualization of contrast agents in the dual-energy mode, slot-scan mammography systems with detectors using narrow x-ray beam to scan the breast can be used. In addition, photon-counting system detectors, which can distinguish photons with high energy from those with low energy levels within a single image, are available.

This technique is still developing and its status within the available imaging techniques is still not defined. There also seems to be debate on whether iodine is the appropriate contrast medium for breast, as the low-energy-level radiation used in mammograms may not give optimal visualization with iodine.

Tomosynthesis. Breast tomosynthesis is a tool that is based on 3D imaging of breast; it involves acquiring images of a stationary compressed breast at multiple angles during a short scan. The images are then reconstructed into thin high-resolution slices that can be displayed on dynamic cine mode. More recently, multislit scanning systems have also been used for this technique, which accomplishes acquisition of multiple projections within a single scan.^[29] In addition, use of a monochromatic x-ray source for the slot-scan system can lead to overall improvement in image quality and reduced radiation exposure.^[30]

The data sourced from tomosynthesis are processed using various reconstruction algorithms.^[31] A study that compared the image quality of tomosynthesis with that of digital mammography found that the image quality of tomosynthesis was equivalent or superior to FFDM in 89% of cases. It also estimated the recall rates of screening mammography when tomosynthesis was also used; it found that recall rates could be reduced to 50% when tomosynthesis was used to supplement mammography.^[32]

Contrast-enhanced mammography and tomosynthesis are both expected to help in more accurate image interpretation, as they largely reduce summation effect. These techniques could help in interpreting mammographic features produced by tissue overlap.

The clinical experiences with both these methods are still limited, but they hold potential to help reduce recall rates, increase cancer detection and improve patient selection for biopsy, especially in patients with dense breasts, where tissue overlap reduces sensitivity of conventional mammograms. The major drawback is susceptibility to motion artifacts and the higher radiation dose to patients.

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