Healthy women possessing a certain abnormality on MRIs are nine times more likely to get breast cancer, according to research published inRadiology. The abnormality is called background parenchymal enhancement (BPE), a phenomenon in which areas of normal background breast tissue appear white, or enhanced.
The magnitude of the link was so strong, it could lead to improved cancer detection and therapy, if future research concurs.
“The degree of the impact of BPE on risk for developing breast cancer was surprising,” senior author, and Seattle Cancer Care Alliance Director of Radiology, Constance Lehman, M.D., Ph.D., FACR, told Bioscience Technology. “While we hypothesized BPE would increase a woman’s risk of developing breast cancer, we did not predict over a 9 fold increased risk.”
The impact may go far beyond finding cancer earlier.
“We are hopeful that interventions to reduce parenchymal enhancement will also reduce a woman’s risk of developing breast cancer,” Lehman said. “MRI may also help target women at increased risk most likely to benefit from chemoprevention, such as with tamoxifen, raloxifene, or aromatase inhibitors. While these medications can reduce a woman’s risk of developing breast cancer, they carry side effects and are not effective in all women. It may be that women with increased BPE are more likely to benefit from chemoprevention than women with minimal or mild BPE. And, it may be that women who respond to chemoprevention with changes in BPE are more likely to benefit from the intervention compared to women in whom BPE does not change with treatment. These are exciting new areas to explore.”
Breast density not key
Lehman’s team analyzed contrast-enhanced MRI (magnetic resonance imaging) images taken between January 2006 and December 2011 from women 18 years or older who were at high risk for breast cancer—but had no history of it. The American Cancer Society advises that women with a 20 percent or greater lifetime risk of developing breast cancer get annual MRIs.
Senior Author Constance Lehman, M.D., Ph.D., FACRLehman’s team zeroed in on both breast density—as high density is considered a risk factor– and BPE (since previous research indicated BPE may be linked to cancer risk).
The upshot was that women with even mildly increased levels of BPE on MRI were nine times more likely to have a breast cancer diagnosis than those without BPE (or with minimal levels). Also unexpected was the fact that breast density had no predictive value.
“A few of our findings were surprising to us,” co-author Habib Rahbar, M.D., toldBioscience Technology. Rahbar is an associate professor with the University of Washington Department of Radiology. Like Lehman, he was taken aback by “the magnitude of the association” between BPE and “breast cancer risk.” Additionally, he said, “because breast density, or amount of fibroglandular tissue, has correlated with breast cancer risk in multiple prior studies, we were surprised it was not associated with risk of developing breast cancer in this study. This may be because patients included in our study were already deemed to be at high risk, and suggests density may not help refine broad categories of risk assessment.”
Said Lehman: “We confirmed what others had reported, but many women and their providers are not aware of: in women already at high risk, breast density confers no additional risk of breast cancer. While there is some increased risk of breast cancer in otherwise average risk women who have dense breast tissue, this association is not evident in women who are at high risk. We found MRI BPE, not mammographic breast density, is the important predictor of risk in women who are already at high risk for breast cancer.
Why does this association appear to exist? As so often recently when cancer questions are posed, inflammation may be an answer. “As opposed to mammography, which primarily provides anatomic information, MRI can provide physiologic insight into normal breast tissue,” Rahbar toldBioscience Technology. “Specifically, by identifying areas of normal tissue that show up as white or bright after administration of contrast, we are able to assess the physiologic activity by looking at blood perfusion of the tissue. Recent pathology literature has demonstrated that the normal tissue environment is perhaps as important as the pre-cancerous duct cells themselves for the promotion of breast cancer formation, and that inflammation in particular may be a culprit in allowing breast cancer to grow. We hypothesize that we are looking at the imaging correlate of inflammation when we see areas of normal tissue brightness on MRI, and that this inflammation is a major factor in the development of breast cancer.”
Lehman explained that the “seed and soil” theory of cancer dates back to the 1800s. “This concept has continued to develop to understand better why cancers can behave so differently in different patients,” she said. “The `seeds’ of cancer cells and the `soil’ or the tissue surrounding the cancer cells are both important to predict outcomes. Not all soil supports cancer seeds to grow. The tumor microenvironment seems to be important in determining the outcome of the cancer, and exciting advances are being made in developing treatments that tackle the tumor microenvironment.” Advanced imaging like the contrast-enhanced breast MRI in her study “may provide important information on the type of environment the breast tissue in an individual patient provides to cancer cells.”
Already at work on the next step
“This was a single center study in a relatively small group of women (23) at increased risk for breast cancer,” said Lehman. “We are eager to have this validated in larger groups of women.”
Agreed Rahbar, their first priority will be to “validate our findings in larger patient populations at different sites with broader breast cancer risk profiles, so we can confirm the clinical utility of our findings. The second will be to determine the biological basis of the finding: is this enhancement of normal tissue related to pathologic markers of inflammation, or other factors that promote breast cancer development?”
Another step has been taken. The study found women with “mild, moderate, and marked” BPE wereallnine times more at-risk. “In truth, the amount of enhancement in a woman’s breast can vary with hormone fluctuations,” Rahbar said. “It is possible even a ‘mild’ amount of enhancement is a marker that they have physiologically active breasts, whereas those who demonstrate minimal to no enhancement do not have this potential.”
Further, Rahbar told Bioscience Technology, “these assessments were determined visually, prone to variations between radiologists and exams. One radiologist’s ‘mild’ may be another’s ‘moderate.’ The best way to get at this is to measure enhancement quantitatively, using computer software. We are exploring this. We presented preliminary findings on a way to quantitatively assess this enhancement at the 2015 American Roentgen Ray Society Annual Meeting in Toronto. The findings are promising, and may allow us to determine a reliable threshold of enhancement that can be determined automatically in order to best predict risk.”
Rahbar said it is too early to recommend for/against MRIs for BPEs.
“But in the future,” he said, “it could reinforce the importance of MRI screening for those at higher risk. We still recommend women 40 years and older to have annual screening mammography, and for those at higher risk to consider breast MRI as a supplemental screening tool to maximize early detection of breast cancer. Any woman concerned about their risk of breast cancer should see a specialist who can determine appropriate screening and prevention strategies. Our study suggests that, in the future, MRIs may become a key component in the equation to precisely determine individual risk, and allow more tailored approaches to breast cancer screening and prevention.”
BPEs may improve “high-risk” criteria
The team’s criteria for defining the “high-risk” women to enroll in their study involved “determination of a lifetime risk of breast cancer of greater than 20 percent using a risk assessment tool based on family history (most commonly the Tyrer-Cuzick model), presence of a known genetic mutation (eg, BRCA1or BRCA2), and/ or history of chest radiation therapy between the ages of 10 and 30 years,” according to the study.
“But a further area of study will assess the average risk population,” concluded Rahbar. “We know current models don’t identify everyone at high risk, and that most women who develop breast cancer were not known to be at high risk prior to being diagnosed. Measuring BPE levels in the breasts of average women may help us identify those at high risk for developing breast cancer, but are missed by traditional models. But we need more research.”