Ductal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Optimal clinical management of DCIS remains controversial, as we are unable to... Show moreDuctal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Optimal clinical management of DCIS remains controversial, as we are unable to identify those DCIS lesions with invasive potential. As a result, current treatment guidelines for DCIS dictate that all women diagnosed with DCIS should undergo treatment to prevent the development of IBC. This makes that many women, who have a low-risk to develop subsequent IBC, are being harmed by this intensive treatment without any benefit. Furthermore, definite proof of DCIS progression to IBC is still lacking.The objectives of this thesis were to identify prognostic markers predictive of the development of subsequent ipsilateral IBC after DCIS and to explore the clonal relatedness of patient-matched DCIS and subsequent ipsilateral IBC. To achieve this, histopathological analysis and molecular profiling were performed using a patient group which was part of a nation-wide population-based cohort including all women diagnosed with and treated for DCIS with breast conserving surgery alone in the Netherlands between 1989 and 2005. The results presented in this thesis will help to stratify a woman’s individual risk of subsequent invasive breast cancer development and will help to avoid overtreatment. Show less
