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Abstract PD3-04: Classic lobular carcinoma in situ in the Netherlands: A population-based analysis

Background: Lobular carcinoma in situ (LCIS) is a non-invasive proliferation of epithelial cells of the terminal-duct lobular unit. Although LCIS is non-invasive itself, studies in the past showed that patients with LCIS have a 4-12 times higher risk of developing invasive breast cancer than the general population. Therefore, the optimal management of LCIS is still subject of debate. Despite lack of information about LCIS in the Dutch population, the Dutch guidelines recommend active surveillance for classic LCIS. This study aims to describe incidence and management of classic LCIS over time in the Netherlands, and to understand its behavior in terms of survival and the risk of developing subsequent ductal carcinoma in situ (DCIS) or invasive breast cancer. Methods: All female patients diagnosed with classic LCIS between 1989-2017 in the Netherlands were identified from the nationwide population-based Netherlands Cancer Registry. Patients previously diagnosed with DCIS or invasive breast cancer were excluded. Standardized incidence ratios (SIR) were calculated to estimate the risk of subsequent DCIS and invasive breast cancer, using data on population size from Statistics Netherlands (CBS). Multivariable Cox proportional hazards regression was performed to estimate hazard ratios (HR) of overall mortality and risk of subsequent invasive breast cancer for different patient-, tumor- and treatment-related characteristics. Competing risks were taken into account. Relative survival was estimated using the Ederer II method, with expected mortality of the general population (matched by age, gender, calendar year) as a reference. Results: We included 1,890 patients. The median age at diagnosis was 51 years (range 24-91 years). The incidence of classic LCIS increased from 186 patients between 1989-1993 to 497 patients between 2014-2017. Of all patients, 50.5% were treated with breast-conserving surgery, 10.2% were treated with mastectomy, 12.6% were treated with an unknown type of surgery and 26.7% did not receive surgery. While in 1989 all patients were surgically treated, only 41% were surgically treated in 2017. Radiotherapy was administered in 3.1% and endocrine therapy in 0.2% of the patients. Median follow-up to death, and subsequent DCIS or invasive breast cancer was 8.5 years (range 0-29 years) and 6.9 years (range 0-27 years). Unadjusted 10- and 20-year overall survival rates were 91% (95%CI:90-93%) and 76% (95%CI:73-79%). Unadjusted 10- and 20-year relative survival rates were 99% (95%CI:97-100%) and 95% (95%CI:91-99%). In total, 270 patients was diagnosed with subsequent invasive breast cancer and 48 were diagnosed with DCIS. Of these, 60% were ipsilateral and 40% were contralateral. The SIRs for DCIS and invasive breast cancer were 4.4 (95%CI:3.2-5.8) and 24.4 (95%CI:21.6-27.5) as compared to the general population, respectively. The SIR was higher for younger patients than for older patients, and the SIR of ipsilateral invasive breast cancer was higher in case no surgical management was performed. In multivariable analysis, increasing age was the most important predictor for overall mortality, while no surgical management was related to a higher incidence of subsequent invasive breast cancer. Conclusion: LCIS incidence has increased over time, while surgical management has decreased. This study shows that the mortality risk is very low compared to the general population. In contrast, the incidence of invasive breast cancer, over a median follow-up of 6.9 years (range 0-27 years), is over 24 times more common in LCIS patients than in the general population. These results suggest that LCIS patients have a good prognosis, even when a subsequent invasive breast cancer is diagnosed. However, the high incidence of second tumors suggest that we carefully monitor these patients. Citation Format: Marissa Corine van Maaren, Agustin Ortega Avila, Jos Bart, Pieter J Westenend, Sabine Siesling. Classic lobular carcinoma in situ in the Netherlands: A population-based analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-04.