Molecular-Based Imaging

Molecular-based imaging technology uses a physiological approach to identify lesions in the breast and can detect mammographically occult cancers.57,58 Gamma detectors are used to image the breast after injection of a radiotracer, technetium sestamibi, which has preferential uptake in highly proliferating tumor cells, thereby identifying functional differences in tumors from normal breast tissue.58-60 Breast-specific γ imaging uses a dedicated, single-head, scintillating sodium iodide detector. Molecular breast imaging is the latest generation of systems and uses cadmium zinc telluride detectors in a dual-head configuration. Although the technologies differ between these 2 systems, the terms are often interchangeably used.58,59 Compared with breast-specific γ imaging, molecular breast imaging has improved rates of count sensitivity, energy resolution, spatial resolution, and lesion detection. In addition, molecular breast imaging requires fewer amounts of injected radiotracer.58 Positron emission mammography is another nuclear medicine system in practice; however, radiotracer uptake increases with breast density, resulting in background parenchymal activity that could obscure underlying malignancies.61

Rechtman et al57 investigated the sensitivity of breast-specific γ imaging for the detection of breast cancer in women with dense vs nondense breasts in 347 biopsy-proven breast cancers, and they determined that the sensitivity rate was similar in women with dense (94.7%) and nondense breasts (96.5%). In addition, mammographically occult breast cancers were equally detected in both groups. The authors concluded that breast-specific γ imaging detected breast cancer regardless of the pathological subtype, nuclear grade, or tumor size.57

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Shermis et al59 retrospectively assessed the clinical performance of molecular breast imaging as a supplementary screening tool for dense breasts in 1,696 women not at high risk and detected 13 mammographically occult malignancies, 11 of which were invasive. The authors reported that the incremental cancer detection rate (7.7%) and positive predictive value for biopsy (19.4%) were higher than that seen with screening ultrasonography.59 They concluded that molecular breast imaging is an acceptable alternative for supplemental screening in women with dense breasts.59 These findings are in line with earlier prospective studies: Data have shown that molecular breast imaging can detect mammographically occult cancers that are primarily invasive and range in size from 2 mm to 5.1 cm.58

Although studies have shown that molecular-based imaging has a high rate of sensitivity for detecting cance in dense breasts, as well as a high positive predictive value, its availability and use as a supplemental imaging tool has been limited secondary to concerns of radiation exposure.58,62 The injected radiotracer delivers radiation throughout the body, including radiosensitive organs beyond the breast. The radiation dose for breast-specific γ imaging has been reported to be more than 5 times that of standard mammography and twice that of standard mammography plus tomosynthesis.62 The radiation dose of molecular-based imaging is 2 to 5 times greater than the dose of mammography, but research has shown promising results using lower doses of radiotracer, which may be more acceptable.58 However, future studies are needed to ensure adequate image quality at this dose.

The total dose of mammography and molecularbased imaging is low (< 10 mSv) compared with the dose associated with adverse-event risk (> 50 mSv), so the benefit may outweigh the risk for some women.58 The only commercially available, FDA-approved biopsy unit is a breast-specific γ imaging system.58 However, biopsy units guided by molecular breast imaging are in development.58,60 Advantages of molecular-based imaging over MRI include its lower cost and fewer contraindications.58,63

Automated Breast Density

Reporting of breast density has implications on the assessment of patient care and risk of breast cancer. However, intraobserver and interobserver variability exist in the visual assessment of the BI-RADS density category selected by the clinician on mammography.1 In response to this challenge, several automated software programs have been developed that measure volumetric breast density. However, quartiles of breast density have been eliminated in the BI-RADS criteria, so the assessment is no longer quantitative and brings into question the utility of quantitative software in the BI-RADS reporting.1 In a retrospective study of 1,185 mammography examinations, Youk et al64 compared the visual assessment of breast density based on the BI-RADS criteria with that of 2 commercially available software programs. They found that more findings on mammography were classified as being nondense with one program and as dense with another program when compared with the findings from the visual assessment.64 By contrast, Ekpo et al65 evaluated one of the programs previously determined to be underestimating. In their study, they compared automated vs visual breast density assessment in 234 women undergoing digital breast tomosynthesis. The authors found a moderate to substantial agreement in breast density assessment between the BI-RADS criteria and the automated software.65 Active research is being conducted to incorporate both automated and visual density assessments into patient risk models, and volumetric breast density measurements may prove to be beneficial in developing algorithms for automated risk assessment.64


Approximately 50% of women have breasts that are at least heterogeneously dense — a figure that amounts to 27.6 million women aged 40 to 75 years in the United States.11 The American College of Radiology identifies breast density as a controversial risk factor for breast cancer with no consensus that it confers sufficient risk to warrant supplemental screening.10 In a position statement from the American Congress of Obstetricians and Gynecologists, dense breasts are identified as a modest risk factor for breast cancer.66 The organization does not recommend routine use of adjunctive studies to screening mammography in asymptomatic women with dense breasts who are without additional risk factors.66

Understanding breast cancer risk conferred by density in the setting of a patient’s history, as well as an appreciation of the imaging tools available, will help aid clinicians in developing the most appropriate screening plan for each of their patients. Mammography remains the most appropriate modality for population-based screening.2,66 One suggested approach for screening women with dense breasts is to use tomosynthesis for all levels of risk, supplemental whole-breast ultrasonography for women with average risk, and supplemental magnetic resonance imaging for women with intermediate and high risk (Figure 6).67 For women who are at high risk and also have a contraindication to magnetic resonance imaging, wholebreast ultrasonography or molecular breast imaging, if available, may be an appropriate alternative. Additional studies are warranted to evaluate optimal supplemental screening strategies, although we suspect that the strategy will likely require a personalized approach based on risk assessment. 

(To view a larger version of Figure 6, click here.)

Shannon Falcon, MD, Angela Williams, MD, R. Jared Weinfurtner, MD, and Jennifer S. Drukteinis, MD 

From the Department of Radiology, H. Lee Mof tt Cancer Center & Research Institute, Tampa, Florida.

Submitted November 29, 2015; accepted February 14, 2016.

Address correspondence to Shannon Falcon, MD, Mof tt Cancer Center, 10920 North McKinley Drive, MKC Third Floor, Room 3002, Tampa, FL 33612. E-mail: [email protected]

No significant relationships exist between the authors and the companies/organizations whose products or services may be referenced in this article. 

From the Department of Radiology, H. Lee Mof tt Cancer Center & Research Institute, Tampa, Florida.

Submitted November 29, 2015; accepted February 14, 2016.

No significant relationships exist between the authors and the companies/organizations whose products or services may be referenced in this article. 


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Source: Cancer Control.
Originally published April, 2017.