A follow-up of GLACIER (a study to investigate the Genetics of LobulAr Carcinoma In situ in EuRope) and ICICLE (A study to Investigate the genetiCs of In situ Carcinoma of the ductaLsubtypE). (ODR1920_145)

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

[1 paragraph unchanged] The following is a summary of the aims of the research project provided by King’s College London: London & Guy's and St. Thomas' NHS Foundation Trust: [1 paragraph unchanged] 1. Ascertain whether any of the genes or SNPs that predispose to lobular breast cancer and DCIS Ductal carcinoma in situ (DCIS) affect survival or progression. 2. Identify tumour biomarkers associated with survival (in ILC) Invasive lobular carcinoma [ILC]) and progression (of LCIS Lobular carcinoma in situ [LCIS] and DCIS to invasive disease). [1 paragraph unchanged] • NDRS Linked Hospital Episode Statistics Admitted Patient Care (HESAPC) – The [21 words unchanged] the NDRS Cancer Registration dataset. Both further disease and recurrences are outcomes we are studying being studied in this project. [4 paragraphs unchanged] The level of the Data will be pseudonymised . • NDRS Cancer Pathways - Data on further breast cancer events is needed in order to determine disease-free and recurrence-free survival in patients for the risk stratification models. The level of the Data will be Identifiable. [1 paragraph unchanged] • Limited to a study cohort identified by the Controller – Individuals recruited into the GLACIER and ICICLE studies between 2007-2013, 2007-2013 at the time, who consented to their information being used in further research. Guy's And St and St. Thomas' NHS Foundation Trust (GSTT) will provide the NHS numbers/other identifiers to NHS England for the participants that consented to further studies from GLACIER & ICICLE. • Limited to all patients with an initial diagnosis date between 1995-2018, with recurrence/death data up to latest 31/12/2021. [5 paragraphs unchanged] King’s College London is the research sponsor and the joint Data Controller with Guy’s and St. Thomas’ NHS Foundation Trust as the organisations responsible for ensuring that the Data will only be processed for the purpose described above. [5 paragraphs unchanged] Data will also be accessed by: a PhD student affiliated with Kings College London. The individual has completed mandatory data protection and confidentiality training and is subject to Kings College London’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of Kings College London. Kings College London would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA). Data will be accessed by substantive employees of KCL and Guy's and St. Thomas' NHS Foundation Trust. [3 paragraphs unchanged]

Processing activities

King’s College London (KCL) Guy's and St. Thomas' NHS Foundation Trust (GSTT) will transfer data to NHS England. The data will consist of identifying details (specifically Name, NHS Number, Date of Birth Birth, and Postcode) Postcode and unique person ID) for the cohort to be linked with NHS England data. NHS England will provide the relevant records from the NDRS HESAPC, NDRS HESOP, NDRS SACT, NDRS RTDS RTDS, NDRS Cancer Registrations and NDRS Cancer Registrations Pathways datasets to KCL. GSTT. The Data provided back to KCL GSTT will contain no direct identifying data items but will contain a unique [8 words unchanged] the Data with other record level data already held by the recipient. [1 paragraph unchanged] The Data and back-ups will be stored on servers at Guy’s Hospital Guy's and St. Thomas' NHS Foundation Trust (on NHS computers). The Data will be accessed by authorised personnel via remote access. [9 paragraphs unchanged] Remote processing will be from secure locations within England/Wales. The Data data will not leave England/Wales at any time. Access is restricted to substantive employees or agents of King’s College London and Guy's and St St. Thomas' NHS Foundation Trust who have authorisation from the Principal Chief Investigator. [4 paragraphs unchanged] Additionally, as per current research funding guidelines, those who consented to their data being used in future research as part of the original study consent will have non-identifiable data deposited in these open access databases; NIH database of Genotypes and Phenotypes (dbGAP) or the European Genome-Phenome Archive (EGA) database, for research purposes, in collaboration with The Breast Cancer Association Consortium. The data that would be deposited would be: 1. Genotype data 2. Age in 5 year intervals 3. Case-control status 4. Sex 5. Study country 6. Study design (e.g. population-based) 7. Genetic ethnicity [2 paragraphs unchanged]

Expected output

[1 paragraph unchanged] • Outputs expected include: • A report of findings to internal Study Team to discuss the future direction of the study. • Reports • Conferences and presentations at breast cancer specific conferences. Conferences in the past include San Antonio Breast Cancer Symposium, PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now), and BCAC (Breast Cancer Association Consortium). • Submissions to peer-reviewed journals • PhD Thesis. • Presentations • Submissions to peer-reviewed journals on an ad-hoc basis. Follow-up results using data from this request already planned to submit to Cancer Epidemiology Biomarkers & Prevention. • Conferences • PhD Thesis [2 paragraphs unchanged] • Journals • Journals. Previously ICICLE and GLACIER studies were published in Cancers, Breast Cancer Research, Cancer Epidemiology Biomarkers & Prevention journals and as this is a follow-up study it is expected that the results would be published in a similar fashion. • Posters and presentations at conferences • Presentations and posters displayed at breast cancer specific conferences, possibly at the ones named above. Both the original studies and the follow-up study have been presented at internal conferences within KCL. [1 paragraph unchanged]

Expected measurable benefits

[1 paragraph unchanged] It is likely that we the analysts will be able to identify risk factors and biomarkers that will allow King’s College London and Guy's and St Thomas' NHS Foundation Trust to predict which people with DCIS Ductal carcinoma in situ (DCIS) and LCIS Lobular carcinoma in situ (LCIS) are likely to develop invasive disease, and which people with invasive lobular [26 words unchanged] progression, while sparing those at low risk from undergoing unnecessary toxic treatment. [2 paragraphs unchanged]

Benefits reported

[2 paragraphs unchanged] Thus far, from the original ICICLE and GLACIER studies novel associations have been found between the occurrence of further breast disease after certain types of in situ breast cancer and single nucleotide polymorphisms. There is also an association between an established breast polygenic risk score (PRS), which is a combination of multiple single nucleotide polymorphisms, and outcomes after in-situ breast cancers. This analysis is being submitted in a manuscript for publication in a peer-reviewed journal, and has the potential to impact surgical and radiological management of in-situ breast lesions especially in those deemed high-risk, personalising treatment and optimising the use of NHS resources for those who are more likely to have further disease. The study also hopes to find other genetic or non-genetic risk factors that could be used to identify those at higher risk of developing further breast cancer through this research, including recurrences on the same side, cancers on the opposite side, invasive cancers or cancers that spread to other sections of the body. The hope is that this research, including already completed analysis as well as associations not yet found, could lead to a reduction in further breast disease, including invasive breast cancer, after in situ breast lesions. But also, the hope is to find a way to identify those that need less treatment, so that patients can make the decision whether or not to take additional hormonal or radiotherapies with a clearer picture of their anticipated risk of further disease.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Data controllers: + KING'S COLLEGE LONDON

Datasets: + NDRS Cancer Pathway

Objective for processing

The study team are conducting a follow-up to the GLACIER and ICICLE studies in order to investigate the survival of breast carcinoma, rates of recurrence and new diagnoses in women with different subtypes of disease. This Data Sharing Agreement (DSA) permits the continued processing of data previously disseminated for the purposes of this study. Guy's And St Thomas' NHS Foundation Trust and King’s College London (KCL) requires access to NHS England data for the purpose of the following research project: A follow-up of GLACIER (a study to investigate the Genetics of LobulAr Carcinoma In situ in EuRope) and ICICLE (A study to Investigate the genetiCs of In situ Carcinoma of the ductaLsubtypE). The aim of the study is to understand survival in participants with lobular carcinoma in situ, invasive lobular carcinoma and ductal carcinoma in situ who were recruited to the GLACIER and ICICLE studies between 2007 and 2013. The following is a summary of the aims of the research project provided by King’s College London: Inclusion Criteria The aim of this project is to collect survival and progression data in women with lobular breast cancer and ductal carcinoma in situ who were recruited to the GLACIER (MREC 06/Q1702/64) and ICICLE (MREC 08/H0502/4) studies. This data will allow KCL to; 1) Subjects will be from the GLACIER and ICICLE studies which originally recruited between 2007-2013, and would have consented to take part in future studies – data on these participants will be requested using NHS numbers or other identifiers already held by the study team. 1. Ascertain whether any of the genes or SNPs that predispose to lobular breast cancer and DCIS affect survival or progression. 2) Aged 60 or less at the time of diagnosis. 2. Identify tumour biomarkers associated with survival (in ILC) and progression (of LCIS and DCIS to invasive disease). 3) Women only. The following NHS England Data will be accessed: For GLACIER: • NDRS Linked Hospital Episode Statistics Admitted Patient Care (HESAPC) – The HESAPC dataset is necessary to work out which patients have had further instances of disease, or recurrences, which aren’t recorded in the NDRS Cancer Registration dataset. Both further disease and recurrences are outcomes we are studying in this project. 4) Cases of invasive lobular carcinoma with or without lobular carcinoma in situ (LCIS) are eligible. The following cases of invasive lobular carcinoma (ILC) are eligible: • NDRS Linked Hospital Episode Outpatient (HESOP) a. All variants of invasive lobular carcinoma are permitted e.g. classical, pleomorphic • NDRS Linked Cancer Registration – This data will allow to identify any further breast disease occurrences in order to determine if patients have experienced the outcomes studied in this project (further disease, contralateral disease, or disease recurrence). b. They can be associated with LCIS or benign breast disease • NDRS Systemic Anti-Cancer Therapy Dataset (SACT) – The SACT dataset is necessary as it not only indicates which patients had systemic therapy, but also gives the treatment indication, which will determine if there were any further events or distant recurrences (indicated by palliative indication). 5) All cases of with current LCIS or past history of LCIS are eligible: • NDRS Radiotherapy Dataset (RTDS) – The RTDS dataset is necessary for this project as it gives treatment intent and region, which allows for identifying and categorising the further breast events by these fields as well as time from the primary event, to determine if the outcomes of interest have been experienced by patients. The RTDS dataset is especially useful in determining laterality where it cannot be determined elsewhere. a. Pure LCIS The level of the Data will be pseudonymised . b. LCIS with subsequent development of invasive breast cancer of any morphological subtype. The Data will be minimised as follows: c. LCIS presenting as an incidental finding together with invasive breast cancer of any morphological subtype. • Limited to a study cohort identified by Controller – Individuals recruited into the GLACIER and ICICLE studies between 2007-2013, who consented to their information being used in further research. Guy's And St Thomas' NHS Foundation Trust will provide the NHS numbers/other identifiers to NHS England for the participants that consented to further studies from GLACIER & ICICLE. Exclusion Criteria • Limited to all patients with an initial diagnosis date between 1995-2018, with recurrence/death data up to 31/12/2021. 1) Over 60 years of age at diagnosis. • Limited to conditions relevant to the study identified by specific ICD or OPCS codes; 2) Male. ICD-10: 3) Mixed ductal/lobular carcinoma cases are not eligible. o C50x and D05x The purposes and means of processing where determined by Guy's and St Thomas' NHS Foundation Trust who is a controller. o C77x-C79x *OPCS codes provided separately [1 paragraph unchanged] Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; controller. [2 paragraphs unchanged] The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out This processing is in the public interest because the project is for scientific research purposes and it is likely to benefit the general population by identifying risk factors and biomarkers that will allow the controllers to predict which people with DCIS and LCIS are likely to develop invasive disease, and which people with invasive lobular cancer are most likely to develop incurable metastatic disease. This will allow more intensive treatment to be given to those at greatest risk to prevent disease progression. Data will also be accessed by: a PhD student affiliated with Kings College London. The individual has completed mandatory data protection and confidentiality training and is subject to Kings College London’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of Kings College London. Kings College London would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA). The Chief Investigator is a member of the Scientific & Medical Advisory Group for Lobular Breast Cancer UK (registered charity) which is a patient-led charity, and pertaining to the lobular breast cancer cases specifically, her involvement in this organisation allows her access to patients who have suffered with this specific form of breast cancer. The GLACIER study has been presented to the members of this organisation. In addition, the Patient Representative for the IMPROVE-DCIS study has also supported use of the data as proposed. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

Processing activities

Data is be stored securely on Guy's & St Thomas' Hospital computers which are password controlled, and access will be limited to those involved directly in this project. King’s College London (KCL) will transfer data to NHS England. The data will consist of identifying details (specifically Name, NHS Number, Date of Birth and Postcode) for the cohort to be linked with NHS England data. Researchers from the Guy's & St Thomas will analyse the Data for the purposes described above. NHS England will provide the relevant records from the NDRS HESAPC, NDRS HESOP, NDRS SACT, NDRS RTDS and NDRS Cancer Registrations datasets to KCL. The Data provided back to KCL will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient. The Data will not be transferred to any other location. The Data will be stored on servers at Guy’s Hospital (on NHS computers). The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract. For remote access: - Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA; - Access controls granting users the minimum level of access required are in place; - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; - Multifactor authentication (MFA) is required for remote access; - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; - All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy. The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose). The Data will not leave England/Wales at any time. Access is restricted to employees or agents of King’s College London and Guy's and St Thomas' NHS Foundation Trust who have authorisation from the Principal Investigator. No other organisation is permitted to access the Data. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. The Data will be linked at person record level (using study ID) with dataset(s) obtained from the GLACIER and ICICLE studies. The identifying details are stored in a separate database to the linked dataset used for analysis, and the identifying details are only accessible by the Chief Investigator. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset. Additionally, as per current research funding guidelines, those who consented to their data being used in future research as part of the original study consent will have non-identifiable data deposited in these open access databases; NIH database of Genotypes and Phenotypes (dbGAP) or the European Genome-Phenome Archive (EGA) database, for research purposes, in collaboration with The Breast Cancer Association Consortium. The data that would be deposited would be: 1. Genotype data 2. Age in 5 year intervals 3. Case-control status 4. Sex 5. Study country 6. Study design (e.g. population-based) 7. Genetic ethnicity All data would be assigned and deposited with randomised IDs and not the original study ID, so that participants cannot be identified. Analysts from the King’s College London and Guy's and St Thomas' NHS Foundation Trust will process the Data for the purposes described above.

Expected output

Outputs expected include: The expected outputs of the processing will be: Reports • Outputs expected include: Submissions to peer-reviewed journals • Reports Presentations • Submissions to peer-reviewed journals Conferences • Presentations PhD Thesis • Conferences For all outputs produced, no identifiable information will be included, and instead will be aggregate numbers within groups. Results will be shared to all sites included with the original studies. • PhD Thesis The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. The outputs will be communicated to relevant recipients through the following dissemination channels: • Journals • Posters and presentations at conferences [1 paragraph unchanged]

Expected measurable benefits

[1 paragraph unchanged] It is likely that we will be able to identify risk factors and biomarkers that will allow King’s College London and Guy's and St Thomas' NHS Foundation Trust to predict which people with DCIS and LCIS are likely to develop invasive disease, and which people with invasive lobular cancer are most likely to develop incurable metastatic disease. This will allow more intensive treatment to be given to those at greatest risk to prevent disease progression, while sparing those at low risk from undergoing unnecessary toxic treatment. It is hoped that through publication of findings in appropriate media, the findings will be publicised (especially as a large cohort of patients in England) to the wider governing bodies and could potentially lead to change of protocol in regards to the breast cancer diseases studied in this project. Guy’s and St Thomas’ NHS Foundation Trust work closely with Cancer Research UK and Breast Cancer Now and any findings will be disseminated through their media departments.

Benefits reported

Thus far, far from the original ICICLE and GLACIER studies, novel associations have been discovered between further disease occurrence after initial diagnosis and the presence of single nucleotide polymorphisms polymorphisms. The data has also allowed for new findings on how genetic factors can impact outcomes after different types of breast cancer.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. The study team are conducting a follow-up to the GLACIER and ICICLE studies in order to investigate the survival of breast carcinoma, rates of recurrence and new diagnoses in women with different subtypes of disease. This Data Sharing Agreement (DSA) permits the continued processing of data previously disseminated for the purposes of this study. The Data Recipient will conduct a follow-up to the GLACIER and ICICLE studies, 5-10 years after the initial recruitment of participants, in order to investigate the survival of breast carcinoma, rates of recurrence and new diagnoses in women with different subtypes of disease. The aim of the study is to understand survival in participants with lobular carcinoma in situ, invasive lobular carcinoma and ductal carcinoma in situ who were recruited to the GLACIER and ICICLE studies between 2007 and 2013. The aim of the study is to obtain survival data on participants with lobular carcinoma in situ, invasive lobular carcinoma and ductal carcinoma in situ who were recruited to the GLACIER and ICICLE studies between 2007 and 2013. Survival data including date and cause of death, follow-up information on recurrence and data relating to new diagnoses will be requested for all women who gave full consent to further studies in order to analyse participants' risk of further disease after breast cancer, or death after breast cancer, according to initial tumour type. [16 paragraphs unchanged] Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out The purposes and means of processing where determined by Guy's and St Thomas' NHS Foundation Trust who is a controller. The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller; The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

Processing activities

Data will be received at Guy's & St Thomas' Hospital (both data controller and processor), only identifiable by original study ID, the linkage of which is held solely by the Chief Investigator. Data is be stored securely on Guy's & St Thomas' Hospital computers which are password controlled, and access will be limited to those involved directly in this project. Data will be stored securely on Guy's & St Thomas' Hospital computers which are password controlled, and access will be limited to those involved directly in this project. Researchers from the Guy's & St Thomas will analyse the Data for the purposes described above. Once received, data will be verified then each participant given another unique identifier. Data will then be cleaned and reshaped into a format which enables analysis, and analysed to answer the study questions. Statistical Analysis The release of NHS England data including date and cause of death, recurrence of breast carcinoma and diagnoses of new cases will allow us to determine the survival-related outcomes of our population of GLACIER participants. In addition filtering to flag where there is a diagnosis of: C77 Secondary and unspecified malignant neoplasm of lymph nodes C78 Secondary malignant neoplasm of respiratory and digestive organs. C79 Secondary malignant neoplasm of other and unspecified sites This will allow the study team to identify patients with secondary cancers not associated with the same procedures as primary breast cancer. This is required as it is difficult for the study team to accurately determine associations with outcomes without knowing if patients had distant metastasis Genetic markers previously identified as predisposing to ILC, LCIS and DCIS, as part of the original GLACIER study, will be tested for association with survival in each of the morphological subtypes of breast cancer included within this follow-up. The data will be requested every two years, for up to five years The results of the analysis will be shared and disseminated.

Expected output

[7 paragraphs unchanged] Outputs are expected to be completed by the end of 2026 (31/12/2026) 2026.

Expected measurable benefits

This data will allow the study to ascertain whether any of the genes investigated in the initial study will increase chances of lobular breast cancer and ductal carcinoma in situ, and affect survival or progression. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. It will also allow the study to identify tumour biomarkers associated with survival in invasive lobular carcinoma, and progression of lobular carcinoma in situ and ductal carcinoma in situ to invasive disease. Having this predictive information on different tumour types could change the way that patients are treated, enabling targeted treatment of different tumour types.

Unchanged: Benefits reported.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: + NDRS Linked HES APC · − Hospital Episode Statistics Admitted Patient Care (HES APC)

Objective for processing

[4 paragraphs unchanged] Inclusion Criteria 1) Subjects will be from the GLACIER and ICICLE studies which originally recruited between 2007-2013, and would have consented to take part in future studies – data on these participants will be requested using NHS numbers or other identifiers already held by the study team. 2) Aged 60 or less at the time of diagnosis. 3) Women only. For GLACIER: 4) Cases of invasive lobular carcinoma with or without lobular carcinoma in situ (LCIS) are eligible. The following cases of invasive lobular carcinoma (ILC) are eligible: a. All variants of invasive lobular carcinoma are permitted e.g. classical, pleomorphic b. They can be associated with LCIS or benign breast disease 5) All cases of with current LCIS or past history of LCIS are eligible: a. Pure LCIS b. LCIS with subsequent development of invasive breast cancer of any morphological subtype. c. LCIS presenting as an incidental finding together with invasive breast cancer of any morphological subtype. Exclusion Criteria 1) Over 60 years of age at diagnosis. 2) Male. 3) Mixed ductal/lobular carcinoma cases are not eligible. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

Processing activities

[4 paragraphs unchanged] Statistical Analysis The release of NHS England data including date and cause of death, recurrence of breast carcinoma and diagnoses of new cases will allow us to determine the survival-related outcomes of our population of GLACIER participants. In addition filtering to flag where there is a diagnosis of: C77 Secondary and unspecified malignant neoplasm of lymph nodes C78 Secondary malignant neoplasm of respiratory and digestive organs. C79 Secondary malignant neoplasm of other and unspecified sites This will allow the study team to identify patients with secondary cancers not associated with the same procedures as primary breast cancer. This is required as it is difficult for the study team to accurately determine associations with outcomes without knowing if patients had distant metastasis Genetic markers previously identified as predisposing to ILC, LCIS and DCIS, as part of the original GLACIER study, will be tested for association with survival in each of the morphological subtypes of breast cancer included within this follow-up. The data will be requested every two years, for up to five years [1 paragraph unchanged]

Expected measurable benefits

This data will allow us the study to ascertain whether any of the genes investigated in the initial study [5 words unchanged] breast cancer and ductal carcinoma in situ, and affect survival or progression. It will also allow us the study to identify tumour biomarkers associated with survival in invasive lobular carcinoma, and progression of lobular carcinoma in situ and ductal carcinoma in situ to invasive disease. [1 paragraph unchanged]

Unchanged: Expected output, Benefits reported.