Researchers Are Investigating Two New Potential Tools for Diagnosing Breast Cancer

Researchers at Jefferson Medical College of Thomas Jefferson University in Philadelphia are investigating contrast-enhanced subharmonic ultrasound as a noninvasive exam that could help physicians make a diagnosis. In subharmonic imaging, pulses are transmitted at one frequency, but only echoes at half that frequency are received

In a study reported in the September 2007 issue of Radiology, researchers tested their technique on 14 women ranging in age from 37 to 66 who had 16 biopsy-proven lesions. The researchers used a GE Logiq 9 ultrasound machine that was modified to perform grayscale subharmonic imaging, transmitting at 4.4 megahertz and receiving at 2.2 megahertz. The women underwent precontrast imaging and imaging using contrast

The researchers’ results using subharmonic imaging were better than conventional ultrasound and mammography. Of the 16 lesions, four were malignant. Mammography had 100% sensitivity and 20% specificity for these lesions. Subharmonic imaging had 75% sensitivity and 83% specificity for the same lesions.

The other tool -
Researchers at Duke University in North Carolina have developed a new scanner that they believe is better at finding early cancers in women than conventional mammography, and it can also be used for diagnosis and monitoring of therapeutic response(s). It is a hybrid between a SPECT and a CT scanner they are collectively calling mammotomography

The researchers have done imaging observer studies using phantoms to compare x-ray digital mammography with CT. “We have been able to show a significant statistical improvement using CT compared to mammography,” Tornai says. “In mammography, you lose a lot of information because you have only a 2D image. With the 3D image that the SPECT/CT scanner produces, lesions become more conspicuous because overlapping tissues are removed. In contrast to x-ray tomosynthesis, a pseudo-3D x-ray imaging modality, the SPECT/CT system produces a uniform 3D image and does not require any breast compression.”

The hybrid scanner that the researchers have built from novel configurations of conventional equipment circles the breast as the patient lies on a specially built table.

The scanner is also able to see areas, including the chest wall, that traditional mammograms may not. They have tested the hybrid scanner extensively with phantoms and has begun successfully scanning subjects with known cancer.

Because SPECT requires IV injection of imaging agents, the SPECT portion of the scanner would not likely be broadly used for routine screening mammography. However, if it proves to be more effective, the hybrid SPECT/CT system might be especially helpful for women who are at high risk for developing breast cancer because of familial history or a genetic predisposition.

Breast SPECT/CT also could be used for women with dense breasts or implants because mammography is known to miss up to 25% of cancers in these women, Tornai says. The scanner and associated imaging procedure also should be less costly to employ than MRI

Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence

Lisa J Martin; Norman F Boyd
An interesting paper published online in Breast Cancer Res. 2008;10(1) by the above authors
This is reported in a Medline article this week

There is now extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The hypotheses that we have developed from the observations described above are summarized here

Cumulative Exposure to Mammographic Density and Breast Cancer Risk

Mammographic density reflects variations in the tissue composition of the breast, and is associated positively with collagen and epithelial and nonepithelial cells, and negatively with fat. Increasing age, parity, and menopause are all associated with reductions in the epithelial and stromal tissues in the breast, and with an increase in fat. These histological changes are reflected in the radiological appearance of the breast, and are consistent with mammographic density being a marker of susceptibility to breast cancer, in a manner similar to the concept of 'breast tissue age' described in the Pike model. Like breast tissue age, variations in mammographic density may reflect the mitotic activity of breast cells and differences in susceptibility to genetic damage, and cumulative exposure to density may have an important influence on breast cancer incidence.

Mitogens, Mutagens and Mammographic Density

Mammographic density is influenced by some hormones and growth factors, as well as by several hormonal interventions, and is associated with urinary levels of a mutagen. We postulate that the combined effects of cell proliferation (mitogenesis) and genetic damage to proliferating cells by mutagens (mutagenesis) may underlie the increased risk for breast cancer associated with extensive mammographic density. As described above under 'Relationship of mitogenesis and mutagenesis', mitogenesis and mutagenesis are not independent processes. Increased cell proliferation can increase lipid peroxidation, and the products of lipid peroxidation can increase cell proliferation

Potential areas for genetic influence include variation in the regulation of the hormones and growth factors that act on the breast, the response and modelling of breast tissue to these stimuli, and the processes that are involved in oxidative stress and the generation of mutagens.

Use of Lidocaine gel pre-mammo may help to reduce discomfort

Compression and the occasional discomfort and pain it brings in the breasts lead many women to avoid mammograms altogether.

However, results from a recent study from Boise, to be published in September 08 edition of Radiology, showed that application of lidocaine gel prior to a mammogram significantly reduced the degree of discomfort experienced.

Lambertz and colleagues recruited 418 women ages 32 to 89 who expected significant discomfort with screening mammography. Fifty-four of the women reported that they had probably or definitely delayed their mammograms due to concern over possible discomfort.

The women were randomized to receive placebos or premedication with acetaminophen, ibuprofen, and/or a local anesthetic gel followed by mammography screening. The gel was applied to the skin of the breasts and chest wall and then removed 30 to 65 minutes before mammography. The gel had no effect on subsequent image quality.

Results showed that oral medication produced no significant differences in breast discomfort, nor did other factors such as breast density. Women who received a topical application of 4% lidocaine gel, however, reported significantly less breast discomfort during mammography.

Eighty-eight percent of study participants indicated they would definitely get a mammogram the following year, and 10% said they would probably get a mammogram the following year.

"Women can now take charge of the situation," Lambertz said. "They can schedule a mammography appointment for a time in their cycle when their breasts are least tender, apply the gel at home, and travel to the appointment knowing they have taken steps toward a positive experience with this potentially life-saving procedure