The studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS)... Show moreThe studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS) studies, unbiased cohorts were used within the international Grand Challenge PRECISION consortium, funded by Cancer Research UK and KWF Dutch Cancer Society. DCIS is graded as low-, intermediate-, or high-grade depending on how abnormal the DCIS-cells look like. However, we showed that pathologists often disagree on grade. To overcome this limitation, we found that almost all DCIS scored as non-high-grade by the majority of pathologists express the estrogen receptor (ER) and are negative for the growth factor receptor HER2, whereas high-grade DCIS is mixed in expression for ER and HER2. We also provided insights in the recurrence risks of DCIS after treatment. See also https://cancergrandchallenges.org/teams/precision.The studies on Invasive Breast Cancer (IBC) were performed on a hospital-based cohort. We found for example substantial variation in tumour response evaluation for HER2-positive IBC after pre-operative chemotherapy due to different guidelines used. For accurate outcome analysis, reducing such variation is mandatory. Therefore, we are working on reaching international consensus of response evaluation. Show less
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
