Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast

Abstract

Background: Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.

Methods: The cohort comprised all women diagnosed with DCIS in the Netherlands during 1989-2004 with follow-up until 2017. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models.

Results: The 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9-32.6) after BCS compared to 18.2% (95% CI 16.3-20.3) following BCS + RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)_{age < 50} 3.2 (95% CI 1.6-6.6); HR_{age ≥ 50} 3.6 (95% CI 2.6-4.8) and for iIBC: HR_age<50 2.1 (95% CI 1.4-3.2); HR_{age ≥ 50} 4.3 (95% CI 3.0-6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HR_{age < 50} 0.7 (95% CI 0.3-1.5); HR_{age ≥ 50} 0.7 (95% CI 0.4-1.3) and for iIBC: HR_{age < 50} 0.6 (95% CI 0.4-0.9); HR_{age ≥ 50} 1.2 (95% CI 0.9-1.6)).

Conclusion: RT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.

Fig. 1. Cumulative incidence with death as the competing risk by treatment strategy.

a In situ and invasive recurrences, b iDCIS only and c invasive recurrences only. *P values are based on Grays’ K sample test.

Fig. 2. Cumulative incidence of iDCIS and iIBC with death as the competing risk splitted for period and age.

Cumulative incidence with death as the competing risk in a iDCIS risk of women <50 years diagnosed between 1989 and 1998 for primary DCIS, b iIBC risk of women <50 years diagnosed between 1989 and 1998 for primary DCIS, c iDCIS risk of women <50 years diagnosed between 1999 and 2004 for primary DCIS and d iIBC risk women <50 years diagnosed between 1999 and 2004 for primary DCIS, e iDCIS risk of women ≥50 years diagnosed between 1989 and 1998, f iIBC risk of women ≥50 years diagnosed between 1989 and 1998, g iDCIS risk of women ≥50 years diagnosed between 1999 and 2004 and h iIBC risk of women ≥50 years diagnosed between 1999 and 2004.