Abstract

We aimed to assess contralateral breast cancer (CBC) risk in patients with ductal carcinoma in situ (DCIS) compared with invasive breast cancer (BC). Women diagnosed with DCIS (N = 28,003) or stage I–III BC (N = 275,836) between 1989 and 2017 were identified from the nationwide Netherlands Cancer Registry. Cumulative incidences were estimated, accounting for competing risks, and hazard ratios (HRs) for metachronous invasive CBC. To evaluate effects of adjuvant systemic therapy and screening, separate analyses were performed for stage I BC without adjuvant systemic therapy and by mode of first BC detection. Multivariable models including clinico-pathological and treatment data were created to assess CBC risk prediction performance in DCIS patients. The 10-year cumulative incidence of invasive CBC was 4.8% for DCIS patients (CBC = 1334). Invasive CBC risk was higher in DCIS patients compared with invasive BC overall (HR = 1.10, 95% confidence interval (CI) = 1.04–1.17), and lower compared with stage I BC without adjuvant systemic therapy (HR = 0.87; 95% CI = 0.82–0.92). In patients diagnosed ≥2011, the HR for invasive CBC was 1.38 (95% CI = 1.35–1.68) after screen-detected DCIS compared with screen-detected invasive BC, and was 2.14 (95% CI = 1.46–3.13) when not screen-detected. The C-index was 0.52 (95% CI = 0.50–0.54) for invasive CBC prediction in DCIS patients. In conclusion, CBC risks are low overall. DCIS patients had a slightly higher risk of invasive CBC compared with invasive BC, likely explained by the risk-reducing effect of (neo)adjuvant systemic therapy among BC patients. For support of clinical decision making more information is needed to differentiate CBC risks among DCIS patients.

Highlights

  • Contralateral breast cancer (CBC) is the most frequent second cancer reported after first invasive breast cancer (BC)[1,2,3]

  • Ductal carcinoma in situ (DCIS) patients had a lower risk of stage IV CBC (HR = 0.45, 95% confidence interval (CI) = 0.22–0.92), and higher risks of grade I invasive CBC (HR = 1.55, 95% CI = 1.31–1.84) and estrogen receptor (ER)-positive invasive CBC (HR = 1.49, 95% CI = 1.33–1.66) compared with all invasive BC patients (Supplementary Table 4)

  • The 10-year cumulative incidence of invasive CBC was 4.8% for DCIS patients, 4.0% for all invasive BC patients, and 5.6% for patients patients was comparable to patients with stage I BC not receiving adjuvant systemic therapy (Supplementary Table 4)

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Summary

Introduction

Contralateral breast cancer (CBC) is the most frequent second cancer reported after first invasive breast cancer (BC)[1,2,3]. The cumulative incidence of invasive CBC for women following invasive BC is ~0.4% per year[4,5,6]. Several studies have shown a decrease in CBC incidence as a result of (neo)adjuvant systemic therapies[6,7,8]. Ductal carcinoma in situ (DCIS) is a potential precursor of invasive BC. As DCIS has an excellent prognosis with a disease-specific survival of >98% at 10 years[12,13,14], a large group of women is at risk of developing CBC

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