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Mathematical Modeling Reveals Value of Active Surveillance in Treating Stage 0 Breast Cancer

By Lina Sorg

Every year in the United States, over 50,000 women are diagnosed with ductal carcinoma in situ (DCIS), also known as stage 0 breast cancer. Although its initial presence is noninvasive, there is currently no way for physicians to determine whether DCIS cell clusters will remain benign or become invasive. Thus, 97 percent of women diagnosed with this earliest form of breast cancer undergo aggressive treatment, while estimates approximate that only 20 to 50 percent of those diagnoses will actually become malignant.

There is rising concern that unnecessarily aggressive treatment, such as surgery and radiation, is detrimental to patient health, according to Shelley Hwang, chief of breast surgery at Duke Cancer Institute (read more of Hwang’s commentary here). Unfortunately, a lack of clinical trials measuring the outcomes in women who choose aggressive treatment versus active surveillance (AS) seems to leave patients no choice.

With this in mind, Hwang and a team of researchers at Duke University designed a mathematical model to help determine if and when AS can be an effective substitute for typical, aggressive treatment. Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, the research team created a risk projection model comparing AS with aggressive treatment as a mortality risk over ten years. Relying on breast cancer progression estimates and natural history parameters, they conducted sensitivity analyses and formulated a 95% projection range to account for parameter uncertainty.

The resulting paper, “Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis,” was published in the Journal of the National Cancer Institute. For women ages 39-41, AS resulted in a heightened risk of death within ten years, when compared to usual treatment. 54-56 year-old women faced a slightly higher risk of death with AS than with aggressive treatment, although the mortality risk with AS was no higher than that of other health problems. But women between the ages of 69 and 71 were at no greater risk of death from AS when compared to normal aggressive treatment, and were about six times less likely to die from breast cancer than from other health problems. Therefore, AS – including screening and hormone therapy – could be advantageous for older women, particularly those with other significant health problems like heart disease.

The model’s outcomes could aid in the future creation of a clinical trial testing AS against aggressive treatment, according to lead author Marc Ryser, who calls AS a “rational trade-off” for certain patients. Although better imaging procedures are still needed, such a trial might ultimately reduce the instance of DCIS overtreatment and increase the efficiency of treatment methods.

Learn more about the study and the researchers’ thoughts here.

 

  Lina Sorg is the associate editor of SIAM News.  

 

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