Study: Molecular profiling may cut breast cancer overtreatment

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As a woman ages, her chances of being diagnosed with a lower-risk breast tumor increase, according to a study published in the December 2011 issue of Breast Cancer Research and Treatment. The study showed that for women over age 50, a substantial number of cancers detected by mammograms have good prognoses.

The study provided the first molecular evidence of an increase in low- or ultra-low-risk cancers in tumors when detected by screening mammography. And it provides a basis for integrating molecular profiling at the time of diagnosis to help avoid overtreatment.

The researchers sought to examine factors behind rising breast cancer rates in the last two decades, particularly among women over age 50. The increase has been attributed in large measure to the widespread use of mammograms, as well as changes in population risk factors such as earlier menstruation, later pregnancies, higher alcohol consumption and, until recently, the use of hormone replacement therapy. This rate has occurred in many countries that have instituted population-based screening, but whether it reflects an actual increase in low-risk tumors or the detection of harmless tumors–or both–has been unclear, according to researchers.

A team based at the University of California, San Francisco (UCSF) collaborated with colleagues at the Netherlands Cancer Institute to analyze the biology of tumors detected more than 20 years ago–before the advent of routine mammography–and tumors detected five years ago, after widespread screening for breast cancer was implemented. They found that mammography appears to reveal slow- to moderate-growth tumors in the population today.

“A significant number of screen-detected tumors are very low risk,’’ wrote Laura Esserman, MD, MBA, director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center. “It shows that we have an opportunity to improve care by using molecular predictors to recognize who has these ultra-low-risk or idle tumors, and safely minimize treatment.

“This information should also help inform radiologists and surgeons about how aggressive we should be in recommending biopsy for low-risk abnormalities seen on mammograms. If most of the cancer we find is low risk, then we may very well be able to test a less aggressive approach for the very low-suspicion findings on mammograms that turn out to be benign. Simple follow up may be the better approach.’’

The ability to identify tumors with little potential for malignancy, the authors wrote, could allow “patients and providers [to] make informed decisions to avoid treatment that may do more harm than good.’’

The researchers utilized MammaPrint, an FDA-approved diagnostic test used by physicians to gauge the risk that a tumor in the breast will metastasize elsewhere.

In their investigation, the researchers focused on three primary questions: Has there been a shift toward the detection of molecularly “good prognosis’’ cancers? Also, is there an increase in the detection of ultra-low-risk tumors, which have an excellent prognosis without treatment, and are these cancers more common in women who have cancers detected by mammograms?

The scientists scrutinized the molecular signature of node negative cancers from 866 patients in Europe. About half of the patients were diagnosed between 1980 and 1991and the other half had lesions diagnosed between 2004 and 2006, after the introduction of population-based screening mammography.

The proportion of poor prognosis tumors varied significantly by age, the authors found, with the likelihood of having a good prognosis growing higher as a woman ages.

The researchers also learned that for women under age 40, who are not routinely screened, the likelihood of good or poor prognosis did not differ between the era before widespread screening and the present time with routine screening. Overall, young women are much more likely to have poor prognosis tumors than older women. However, for tumors in patients aged 49 to 60, when comparing the two time periods, there was a substantial increase in good prognosis tumors for women diagnosed more recently.

The study “provides information that will allow us to improve screening,’’ the authors concluded. “Not only can this help us to guide the use of risk stratifying tools to avoid overtreatment, but it should also enable us to reset thresholds for biopsy for very low-risk mammographic lesions.’’