Rethinking breast cancer risks: Study expands understanding of DCIS mortality

In the discussions and debates around the optimal breast cancer screening strategies, overdiagnosis and overtreatment concerns loom large. Now, a study published in JAMA Oncology might be cause to reevaluate the detection and treatment of ductal carcinoma in situ (DCIS), or stage 0 cancer.

Specifically, despite a general belief that DCIS is a preinvasive neoplastic lesion that is not lethal in itself, researchers found these cases might have more in common with small invasive cancers than previously thought.

“Some cases of DCIS have an inherent potential for distant metastatic spread,” wrote Steven A. Narod, MD, of the University of Toronto and Women’s College Hospital in Toronto, and colleagues. “It is therefore appropriate to consider these as de facto breast cancers and not as preinvasive markers predictive of a subsequent invasive cancer.”

The authors found that the breast cancer-specific mortality rate of those with DCIS was 3.3 percent at 20 years of follow-up. At the same time, aggressive treatment with radiotherapy or mastectomy to reduce recurrence did not reduce breast cancer mortality.

The findings are especially important in today’s screening environment, where 20 percent of cancers discovered by mammography are DCIS.

Narod and colleagues tapped the Surveillance, Epidemiology, and End Results database for cases of DCIS diagnosis from 1988 to 2011, including 108,196 women in the analysis.

Results showed that for women diagnosed with DCIS, the risk of dying from breast cancer increased 18.1 times after experiencing an ipsilateral invasive cancer.

Among those who received lumpectomy, radiotherapy was associated with a nearly 50 percent reduction of ipsilateral invasive recurrence at 10 years (2.5 percent vs 4.9 percent), but it surprisingly did not significantly reduce breast cancer-specific mortality at 10 years (0.8 percent vs 0.9 percent). Likewise, unilateral mastectomy cut the risk of ipsilateral invasive recurrence at 10 years from 3.3 percent to 1.3 percent, but these patients had slightly higher breast cancer-specific mortality (1.3 percent vs 0.8 percent).

A total of 517 patients died of breast cancer following a DCIS diagnosis but without experiencing an in-breast invasive cancer.

Breast cancer-specific mortality was impacted by age; only 1.2 percent of the women in the study received a DCIS diagnosis before age 35, but their breast cancer mortality was 7.8 percent compared with 3.2 percent for older women. Black women also had a higher mortality of 7 percent, compared with 3 percent for non-Hispanic whites.

Narod and colleagues noted several similarities between the clinical course of patients with DCIS and those with small invasive cancers, pointing out that for both:

• Tumor size and grade are significant predictors of mortality;
• Women with ER-positive cancers had initially lower annual hazard ratios, but that this relationship between ER status and annual mortality later reverses;
• Women receiving a diagnosis before age 40 black women have fare less well than older women and white women, respectively; and
• Mortality increases after invasive in-breast recurrence.

In an associated editorial, Laura Esserman, MD, MBA, and Christina Yau, PhD, both of the University of California, San Francisco, wrote that the study should spur further investigations to better understand the biological characteristic of the highest-risk cases of DCIS and test targeted approaches, while also suggesting that some current therapies should not be routinely offered.

“Given the low breast cancer mortality risk, we should stop telling women that DCIS is an emergency and that they should schedule definitive surgery within two weeks of diagnosis,” wrote Esserman and Yau.

“Ductal carcinoma in situ may best represent an opportunity to alter the environment of the breast. For the lowest-risk lesions, observation and prevention interventions alone should be tested.”