Breast Enhanced Scintigraphy reveals beneficial metabolic changes correlating with reduced inflammation after 8 months of soy supplementation. Mean Count Activity (MCA) was reduced in both breasts (top L and R) compared with baseline measurements 8 months earlier (bottom L and R). Courtesy of Dr. Richard M. Fleming, Fleming Heart & Health Institute, Omaha, NE.

SAN DIEGO—A new scintigraphic imaging technique able to detect premalignant changes in breast tissue has revealed that soy supplementation can partially reverse these changes, offering the first objective physiological evidence that increased soy consumption may have a role in preventing breast cancer.

Breast Enhanced Scintigraphy Testing (BEST) is a variant of SPECT imaging that identifies differences in mitochondrial activity throughout breast tissue. Areas of rapidly-dividing premalignant or malignant cells show increased mitochondrial activity when compared with normal tissue, explained Richard M. Fleming, MD, an Omaha, Nebraska, nuclear and preventive cardiologist who developed the technique.

Speaking at the 4th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, Dr. Fleming said he initially pioneered this technology as a myocardial assessment tool. But women coming in for cardiovascular work-ups repeatedly asked why they needed to have separate mammographic assessments when their chests were already being scanned for cardiovascular disease. This set Dr. Fleming thinking that this new tool could be applied to breast evaluations as well.

BEST involves infusion of a radioactive sestamibi isotope that is taken up by mitochondria. Tissue uptake of the marker is directly correlated with increased blood flow, increased cellular metabolic activity and higher mitotic rates. It also shows inflammatory changes associated with premalignancy. A computerized technique, BEST is highly reproducible. “The computer takes all the subjectivity out of it,” he said.

Dr. Fleming’s initial study involved 197 women and 3 men, and compared BEST assessment of mammary tissue with biopsy-based pathologic assessment. In total, there were 84 normal subjects, 104 showing inflammatory or premalignant changes, and 12 who had cancers. The correlation between BEST and biopsy was near 100%.

BEST images of normal breasts, with MCAs of 143 in the left breast (top) and 154 in the right (middle). Bright spot in upper right of images is a reference point source of Technetium, 400 microcuries, having an MCA of 1044. Courtesy of Dr. Richard M. Fleming, Fleming Heart & Health Institute, Omaha, NE.

The technique is particularly valuable because it can detect early metabolic changes. A maximal count activity (MCA) score of 300 on BEST correlates strongly with atypia and metaplasia. “You don’t just go from no disease to breast cancer. There are a lot of earlier transitions.”

The good news is, soy supplementation appears to down-regulate these premalignant metabolic changes, and Dr. Fleming hopes that BEST will provide enough objective evidence to finally put to rest the contentious debate over whether soy is beneficial or harmful for women at risk of breast cancer.

He randomized 87 of the women from his original study who had inflammatory, premalignant changes on BEST to either their normal diets or their normal diets plus daily supplementation with 24 grams of a powdered soy supplement (Revival Soy), which the women mixed as a drink. The supplement contains 160 mg total isoflavones per day, and 1,000 mg saponins.

Dr. Fleming stressed that this is independent, self-funded research, and that he has not received financing from any soy product companies or any other commercial interests.

A total of 40 women were randomized to the supplementation arm, which was continued for 6 months. To date, he has obtained follow-up BEST scans on 30 of the 40 patients. They show a strong trend toward reduced metabolic activity in previously abnormal tissue.

Before supplementation, the mean MCA score for the 30 patients was 245 ± 40; after 6 months of daily soy consumption, MCA dropped to 201 ± 20. “This is still in the inflammatory range, but the trend is downward, and there are no women that we’ve seen so far who’ve shown an increase in MCA following soy.”

Citing one patient as a typical example, he noted that the baseline mean activity score was 280 for her right breast; after 6 months on Revival soy, the score dropped to 177. Subjects not treated with soy showed no consistent MCA changes over the 6 month period. Dr. Fleming noted that in the soy group, the observed MCA changes were, “unrelated to menstrual cycling or anything else we could see.”

The mechanism by which soy influences breast tissue metabolism is largely unknown. He hypothesized that it might be related to inhibition of angiogenesis, but it may equally reflect direct metabolic or anti-inflammatory effects related to the L-arginine content of soy.

“My personal bias is that there is more than one thing, more than one mechanism. Clearly soy itself has benefit, but it is probably not due to just one single thing. Soy affects many different pathways simultaneously.”

He acknowledged that there are still many unanswered questions: Can soy prevent recurrence of breast cancers? Can it inhibit the growth of secondary cancers or metastases? Does it promote natural killer cell activity? Is it safe to give soy to women who have confirmed breast cancer?

“This is only the tip of the iceberg,” Dr. Fleming told symposium participants. But with the advent of BEST, researchers now have an objective, reliable tool for directly measuring the metabolic effects of soy or nutritional interventions.

BEST has FDA clearance as a method for cardiovascular and breast assessment. Currently, Dr. Fleming’s Heart and Health Institute in Omaha is the only center offering BEST, but he hopes it will soon be available at 4 or 5 major medical centers throughout the country at some point during this year. Free patient samples of Revival Soy are available at: www.soy.md.

THE REDUX: A new scintigraphic technique that detects inflammatory and premalignant changes in breast tissue is providing a window onto the effects of soy in reducing risk of mammary cancers. Breast Enhanced Scintigraphic Testing (BEST) revealed that women with premalignant lesions who consumed a soy supplement containing 160 mg isoflavones per day showed marked and measurable reductions in inflammation and metabolic activity in these lesions after 6 months.