Linking patient outcomes to genomic data in the ICICLE and GLACIER trials to determine how inherited variation influence recurrence after in situ breast cancer

Lead Supervisor
Professsor Elinor Sawyer
Professor and Honorary Clinical Oncologist
Innovation Hub, School of  Cancer & Pharmaceutical Sciences, FoLSM, King’s College London

Professor Marjanka Schmidt
Professor of genetic epidemiology of breast cancer
The Netherlands Cancer Institute, Amsterdam

Project Details

In situ breast cancers are diagnosed in ~ 8000 women yearly in the UK and consist of two subtypes: ductal carcinoma in situ (DCIS), which accounts for 20% of screen detected breast cancer, and lobular carcinoma in situ (LCIS). The importance of these diagnoses rests on the increased risk of subsequently developing invasive breast cancer. In studies where DCIS has been treated with lumpectomy alone, 30% of women develop an ipsilateral recurrence at 10 years and this can be reduced by giving radiotherapy. The risk for women with LCIS is less, with a 2.4 times increased risk of invasive breast cancer compared to the general population. Both LCIS and DCIS are also risk factors for developing invasive cancer in the contralateral breast. Currently the histological features of the in situ lesions are used to decide which women need treatment however these are poor at predicting recurrence. This results in many DCIS cases being over treated and some LCIS cases being under treated. 

The aim of this project is to link recurrence and survival data from Public Health England in 5000 women with in situ breast cancer to genomic data generated through the GLACIER (MREC 06/Q1702/64) and ICICLE (MREC 08/H0502/4) studies in order to ascertain whether inherited genetic variants affect recurrence or survival in these breast cancer subtypes. 

These studies collected detailed data on standard risk factor data as well as blood and tumour samples from 3000 women with DCIS and 2000 women with LCIS +/- invasive lobular cancer from 97 UK hospitals. As the primary objective of these studies was the identification of inherited genetic variation that predisposed to in situ breast cancer, genome wide single nucleotide polymorphism (SNP) analysis and sequencing of BRCA1, BRCA2, PALB2, CHEK2 and CDH1 has been performed on the germline DNA from all these women. These analyses have shown that the SNPs and genes that predispose to invasive breast cancer also predispose to in situ breast cancer.

A combination of 313 breast cancer predisposition SNPs can be used to predict the likelihood of developing invasive breast cancer. However, it is not known whether this polygenic risk score can predict the risk of invasive breast cancer after a diagnosis of DCIS/LCIS and what the relevance for prognosis is. In invasive breast cancer previous studies have suggested that SNPs may also influence survival and response to treatment, but there is no data on whether this effect is also seen in DCIS/LCIS. 

The GLACIER and ICICLE studies are uniquely positioned to answer these questions however follow up data on the women recruited to these studies is lacking. Data has therefore been requested from the NCRAS, HES, SACT and RTDS data sets in order to ascertain further events in the 5000 women recruited to these studies and develop a comprehensive risk prediction algorithm which includes inherited genetic factors as well as the molecular characteristics of the primary in situ lesions in order to individualize treatment and follow up for women with in situ disease. 


Datasets have been requested from: National Cancer Registration and Analysis Service ‚Äì Patient, Tumour and Treatment Data Sets:  Linked Hospital Episode Statistics  – Inpatient Data Set;  Systemic Anti-Cancer Therapy Data Set;  Radiotherapy Data Set. All the ethical information governance approvals are place.


In situ breast cancer, genetic predisposition, breast cancer recurrence and survival