Abstract P5-08-15: The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review
Authors: Alaeikhanehshir Sena , Engelhardt Ellen G , van Duijnhoven Frederieke H , van Seijen Maartje , Bhairosing Patrick A , Pinto Donna , Collyar Deborah , Wesseling Jelle , Lips Esther H , Schmidt Marjanka K 
Published: March 2020

Purpose The majority of ‘low-risk’ (grade I/II) Ductal Carcinoma In Situ (DCIS) lesions do not progress to invasive breast cancer during a woman’s lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for grade I/II DCIS is being evaluated in several clinical trials. If active surveillance is proven safe and implemented in clinical practice, a significant group of women with low-risk DCIS may forego surgery and radiotherapy. To further reduce their risks, there is an urgent need to identify potentially modifiable risk factors. Nonetheless, non-modifiable risk factors are also of great importance to gain clear understanding of the overall risk for developing a subsequent event (invasive breast cancer, in situ recurrences, distant metastases) following untreated DCIS. A systematic literature review was performed to evaluate the impact of established breast cancer risk factors on the risk of developing in situ or invasive disease after treatment of primary pure DCIS. Methods A systematic literature search was performed in PUBMED, EMBASE and Web of Science. PRISMA methodology was applied for the selection of studies. We only included studies that were published after the review by Shamliyan et al in 2010. Results Nine out of the 3,852 articles retrieved were included for final data extraction and evaluation. These nine studies included a total of 11,602 patients with primary pure DCIS. The sample size of these studies ranged from 50 to 4,131 patients. Across the studies, a total of 979 (range: 2-239) subsequent events, such as ipsilateral invasive, ipsilateral in situ events, and distant metastases, were reported. The median follow-up varied between four and nine years. There was limited information published and limited evidence in the selected studies especially on modifiable factors; and all studies except one, were in women of European-descent. Of the modifiable factors only a high BMI (≥25) in mainly postmenopausal women seemed to be associated with a lower risk of a subsequent event. There was some evidence for several non-modifiable predictors, i.e. younger age at diagnosis of DCIS, positive family history of breast cancer, premenopausal status, and high breast density. Age was associated with a two to threefold risk for experiencing a subsequent event. A positive family history had an almost two-fold increased risk, and pre-menopausal status increased the risk for a subsequent event between 46 to 89%. Furthermore, the highest quintile for breast density was associated with a 70% increase in risk for a subsequent event. See table 1 for effect sizes with 95% confidence intervals. Conclusion There is a limited number of studies published on the impact of risk factors on subsequent events after pure DCIS. Moreover, the available evidence is insufficient to identify potential targets for risk reduction strategies, due to the relatively small numbers and the lack of long term follow-up in a low-event disease such as DCIS. Traditional risk factors for primary invasive breast cancer showed, in general, also to be associated with the risk for a subsequent event after primary pure DCIS. The single study that reported on BMI showed a direction of association that was contrary to expectations. In conclusion large scale, well-designed, studies with specific attention to lifestyle factors are necessary to enable identification of DCIS who are at low and high risk for a subsequent event after primary pure DCIS.

Table 1. Overview of published effect sizes of risk of a subsequent event after pure DCISIncluded articlesVariableHR/OR (95% CI)Moran et al. 2017 Age (≥50 vs &lt; 50 years) HR(Multivariate) 0.54 (0.41-0.71)Alvarado et al. 2012Age (&lt;40 vs ≥ 40 years)HR(Univariate) 2.70 (1.06–6.93) Baglia et al. 2018Family history (&gt;2 relatives with Breast Cancer)OR(Multivariate) 1.78 (1.02–3.10)De Lorenzi et al. 2018BMI (high ≥ 25 vs low)HR(Multivariate)0.48(0.26-0.90)De Lorenzi et al. 2018Menopausal state (pre vs post)HR(Multivariate)1.89 (0.37-0.77)Shurell et al. 2017Menopausal state (post vs pre)HR(Multivariate)0.54 (0.37-0.77)Habel et al. 2010Breast density (highest quintile)HR(Multivariate)1.70 (1.00–2.39)

Citation Format: Sena Alaeikhanehshir, Ellen G Engelhardt, Frederieke H van Duijnhoven, Maartje van Seijen, Patrick A Bhairosing, Donna Pinto, Deborah Collyar, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt. The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review [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 P5-08-15.