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The incidence of invasive breast cancer after conservative treatment for ductal carcinoma in situ (DCIS) decreased by more than 50% over the past 30 years, data from a Dutch cancer registry showed.

Among 19,000 patients who received radiation therapy (RT) after lumpectomy, the 10-year incidence of invasive ipsilateral breast cancer (iIBC) decreased from 5.7% during 1989-1998 to 2.3% from 2009-2021. Without RT, the incidence of invasive recurrence remained about twice as high, but declined over time from 12.6% during 1989-1998 to 5.0% during 2009-2021.

DCIS histologic grade did not significantly influence the risk of iIBC or the grade of the recurrent disease, reported Adri Voogd, PhD, of Maastricht University, during the European Breast Cancer Conference.

"We see a really remarkable decrease in the risk of invasive relapse, which is due to the success of the treatment, of course, but also to the increasing number of patients with really small DCIS lesions," said Voogd. "We don't see any association between DCIS grade and the risk of invasive relapse, which stresses the need for powerful predictive and prognostic factors to guide the treatment but also to guide the clinical follow-up of patients with DCIS."

When discussing DCIS treatment options for patients, clinicians should consider these findings within a broader context of breast cancer risk, said invited discussant Frederieke van Duijnhoven, MD, of the Netherlands Cancer Institute in Amsterdam. A healthy, cancer-free 50-year-old woman has a 10-year breast cancer risk of 2.4%, and for a healthy 60-year-old, the risk is 3.54%.

"These are patients who have been screened in a national breast cancer screening program," said van Duijnhoven. "If you've had DCIS, Dr. Voogd has shown us the risk is 2.3%, if you've received treatment. Perhaps we should adopt follow-up intensity. Also, in the back of my mind, sometimes in the front, is the effect of body weight and smoking. Those factors seem to be more dangerous to me than DCIS."

The correlation between DCIS grade and breast cancer is weak, but the data from the current study show that a person with grade III DCIS is more likely to develop grade III breast cancer than is someone with DCIS grade I or II, suggesting "we have to be a little bit cautious about omitting radiation in this group of patients," van Duijnhoven noted.

"For sure, the most important thing would be to have more reliable prognostic and predictive factors, not only from a translational research precision project, but genomic risk assessments may also be of use in this respect," she added. "Finally, we should not confuse the risk of progression if you don't do anything -- a wait-and-see strategy -- and the risk of recurrence, which could also include a second primary tumor. These are two entirely different things, and we need different information to discuss with the patients."

"For now, the wait-and-see strategy seems suitable only for grade I and II disease," she said.

The incidence of DCIS has "exploded" with the introduction of national screening programs, Voogd said while providing background for the study. In the Netherlands, the incidence of DCIS has increased sixfold since 1989. However, limited data exist regarding the relationship between DCIS and risk of iIBC after breast-conserving surgery for DCIS with or without RT. The same is true for the association between DCIS grade and the risk of iIBC.

To address the lack of informative data, investigators queried the Netherlands Cancer Registry and identified 25,719 women who had DCIS diagnoses from 1989 to 2021. All the patients were treated with breast-conserving surgery, which included adjuvant RT in 19,034 (74%) cases.

An analysis of trends in adjuvant RT by DCIS grade showed that no patient with grade I DCIS received RT during 1989-1993. The rate increased thereafter, reaching 65-70% in the early and mid-2000s before declining to 22% during 2019-2021. For grade II DCIS, the proportion of patients receiving adjuvant RT ranged from 65-90% across the study period, with the exception of 50% during 1994-1998. For grade III, breast-conserving surgery included adjuvant RT in 88-96% of cases from 2004-2021.

Among patients who received adjuvant RT, iIBC incidence was 5.7% during 1989-1998, 3.7% during 1999-2008, and 2.3% from 2009-2021 (P<0.0001). Rates for the same time periods without adjuvant RT were 12.6%, 9.0%, and 5.0% (P<0.0001).

Voogd and colleagues found no association between iIBC and DCIS grade. Using grade I DCIS as the reference, they found hazard ratios of 1.10 (95% CI 0.86-1.50) and 1.05 (95% CI 0.80-1.37) for grades II and III in the patients who received RT and hazard ratios of 0.93 (95% CI 0.70-1.22) and 1.11 (95% CI 0.84-1.48) for the patients who did not receive adjuvant RT.

Comparing DCIS grade with iIBC grade, they found that the 29% of patients with grade I DCIS (n=189) also had grade I iIBC, 59% had grade II iIBC, and 12% had grade III. In the grade II DCIS subgroup (n=256), 22% had grade I iIBC, 54% had grade II iIBC, and 24% had grade III iIBC. In the grade III DCIS group (n=276), 10% of patients had grade I iIBC, 45% had grade II, and 45% had grade III.

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