Each year, over 60,000 women in the US are confronted with a diagnosis of ductal carcinoma in situ (DCIS) of the breast. DCIS is a potential precursor of invasive breast cancer (IBC). Over 80% is found by mammographic, population-based screening, because many DCIS-lesions are associated with calcifications seen on mammography. Due to screening, the DCIS incidence has increased substantially. However, due to screening has not resulted in a decrease of breast cancer-related mortality. In fact, four out of five DCIS lesions will never make it to IBC. This implies that part of the DCIS lesions can be considered as overdiagnosis, putting women at risk of overtreatment. We are identifying subsets of DCIS patients with a very low risk of developing an IBC to define possible alternative treatment strategies for this subgroup of very low risk DCIS-lesions, such as a wait and see policy.
First, we have evaluated the risk of developing ipsilateral and contralateral invasive breast cancer after treatment of primary DCIS in a nationwide retrospective cohort study (n = 10,096).
Second, we conducted a nested case-control study to identify subsets of DCIS patients with a very low risk of developing an invasive ipsilateral breast cancer. We have collected tissue blocks and pathology reports of over 1,100 DCIS samples and 247 subsequent invasive breast cancers. DNA and RNA were isolated from the tissue samples for subsequent molecular analysis. Data analysis is in progress to find biomarker that can distinguish harmless from aggressive in situ breast lesions, which may aid to decide which woman should be treated and which one not.
Third, we run a randomized controlled, phase 3 non-inferiority trial in mainland Europe to evaluate the safety of active surveillance in 1,240 women with low grade DCIS. The LORD trial is coordinated by the BOOG and EORTC. For this trial, we received the Value-Based Health Care Dragon grant
For our DCIS research, he received the 20-million-dollar Cancer Research UK Grand Challenge/KWF Dutch Cancer Society Award ‘When is cancer not really cancer’ in 2017 for his initiative to set up a global team of the best experts in the world to conquer DCIS overtreatment (www.dcisprecision.org).
To ensure effective cytotoxic or targeted systemic treatment of breast cancer patients, it is essential to develop and improve predictive diagnostic tests to achieve the best benefit-to-harm ratio. To do so, we also design tests predicting response to preoperative chemotherapy. Therefore, we collect pre-treatment biopsy material with clinical and pathological data from all patients receiving neoadjuvant chemotherapy in the NKI-AVL since 2004 resulting in a database with over 1,300 patients. The main finding thus far is the association between a BRCA-like genomic profile and a remarkably better response to high dose chemotherapy. To assess this BRCA-like genomic profile in routine diagnostics we developed an easy to perform MLPA assay. This assay is now used in multiple different clinical multi-center trials for high dose chemotherapy as well as for daily diagnostic purposes. In addition, we are identifying biomarkers for trastuzumab response in HER2-positive breast cancer in close collaboration with the medical oncology department at the Antoni van Leeuwenhoek (Gabe Sonke).