A national population-based case-control study of the genetic environment and behavioural causes of breast cancer in men ( ODR1617_370 )

Institute of Cancer Research (a charity) requires access to NHS England data for the purpose of the following research project:

A national population-based case-control study of the genetic environment and behavioural causes of breast cancer in men.

The following is a summary of the aims of the research project provided by Institute of Cancer Research:

The Institute of Cancer Research will access patient-level cancer registration data recorded by the National Cancer Registration and Analysis Service for a case-control study into the genetic, environmental and behavioural causes of breast cancer among men in England and Wales (MREC reference: 07/MREC01/1).

Although breast cancer is the most common cancer in women, it also occurs less commonly in men. In total, there are about 280 cases each year in men in the UK.

Following identification by the National Cancer Registration and Analysis Service, the Institute of Cancer Research will recruit male breast cancer patients into a case-control study. Recruitment will take a total of 14 years to give around 2,100 cases in all. To support recruitment, data (such as the patient’s name, address and GP) will be provided to the Institute of Cancer Research on all men with breast cancer newly diagnosed at ages 18-79 and resident in England and Wales. These data will be used to identify men who are eligible to be invited men to participate via their consultant oncologist or GP and to gain their consent to be part of the study. Once consented into the study, these men will be asked to list to a nurse-interviewer, all male non-blood relatives within certain fixed relationship categories who will be invited to be controls.

Cases and controls will be interviewed by a research nurse about potential risk factors for male breast cancer (with a family history form sent in advance, because we have found that this facilitates the interview), a 27 ml blood sample (and/or buccal swab) would be taken, height and sitting height would be measured, and, for cases, informed consent would be requested to extract data from their case-notes and to gain access to the pathology specimen.

The case-control population will be used to better understand the risks of male breast cancer, overall and by oestrogen-receptor status, in relation to (a) environmental and behavioural factors, (b) potential susceptibility genes and polymorphisms, and gene-environment interactions and (c) risks of breast cancer in women first degree relatives of men with breast cancer according to the relationship and the genotype of the man.

The following NHS England Data will be accessed:

• Cancer Registration – necessary because of the condition relevant to the study is breast cancer.

The level of the Data is:

• Identifiable – necessary to identify potential participants of the research study. These data need to be retained during the study to prevent duplicate approaches to patients. Furthermore, inclusion of patients who have died (if the diagnosis was only made post-mortem).

The data was minimised as follows:

Limited to a study cohort identified by NHS England (formerly by PHE and National Cancer Registration and Analysis Service) as meeting the following criteria:

• male adults aged 18–79 newly diagnosed breast cancer between January 2005 - Aug 2017

• conditions relevant to the study identified by specific ICD code C50 (men diagnosed with breast cancer)

• Limited to the following geographic areas: England and Wales.

Institute of Cancer Research is the Controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

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.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

Breast Cancer Now (the original funder) has no further involvement with the project. The funding for ongoing work is provided by the Tridgell Fund. The funding is specifically for the project described. Funding is in place until 2026. Further funding will be requested to continue the project beyond this date. The funder will have no ability to suppress or otherwise limit the publication of findings.

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 has not been disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

Institute of Cancer Research holds the relevant records from the NDRS Cancer registration dataset. The Data contains directly identifying data items including Names, NHS Number, Date of Birth, Postcode, Gender which were required to identify men diagnosed with breast cancer. This information has been used to approach potential participants of this research study. All patients were invited through their doctors, once eligibility was confirmed.

No additional data will be disseminated by NHS England for the purposes of this DSA.

The Data will not be transferred to any other location.

The Data will be stored on servers at Institute of Cancer Research.

The Data will be accessed onsite at the premises of Institute of Cancer Research only.

The Data will not leave England at any time.

Access is restricted to employees or agents of Institute of Cancer Research who have authorisation from the Principle Investigator.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data was linked with NHS named information such as from case-notes, clinical staff enquiries and other relevant data sources in current NHS systems.

There will be no requirement and no attempt to reidentify individuals when using the Data.

Analysts/researchers from the Institute of Cancer Research will process/analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to patient-centred charities (e.g. Breast Cancer NOW) and help groups

• Publication in peer reviewed journals

• Presentations to patient and lay groups

• Presentations at appropriate (cancer) conferences

• Publication on Institute of Cancer Research website;

• press releases and blogs

• meetings and seminars.

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 from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Public reports

• Press/media engagement

• Reports aimed at participants/patients

• Scientific publications could inform NICE guidelines (e.g. Familial Breast Cancer).

Additional analyses of the data are ongoing and planned. Future outputs will include published papers in high-profile peer-reviewed scientific journals on risk factors for male breast cancer and survival with a target date for production and dissemination of the outputs by 2034.

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.

The use of the data could:

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as obesity and diabetes.

• inform decisions on how to effectively allocate and evaluate funding according to health needs.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

This is the largest case-control interview study of the causes of breast cancer in men and therefore able to provide for patients, their families, their doctors and the public, far better data on risks of male breast cancer than previously available. Analyses include the genetic variants that increase risk of breast cancer in men, lifestyle risk factors, and male infertility risk.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients. Clients will need to take action based on the information provided to them in order to realise the potential improvement opportunities. For example, someone identified as high risk could use diet and exercise to reduce some of their risk factors.

Although breast cancer is the most common cancer in women, it also occurs less commonly in men. There are about 280 cases per year in men in the UK. Both in terms of genetic factors and environmental/behavioural factors, there is evidence of a differences in risk factors between men and women, that warrant the investigation in men. In addition, findings from studies in men may illuminate aetiology in women from a novel angle, especially as risk factors in men can be examined without confounding by menstrual factors and childbearing.

The main findings of the study were:

1. Sex chromosome aneuploidy, largely Y chromosome loss, increased sharply and highly significantly with age.

2. Klinefelter syndrome and gynecomastia were statistically significantly associated with risk. Diabetes emerged as an independent risk factor.

3. Tobacco and alcohol do not appear to be carcinogenic for male breast cancer.

4. Men can be identified as high genetic risk of breast cancer: These men have a four-fold increased risk of breast cancer.

5. Obesity at all adult ages, particularly recent abdominal obesity, is associated with raised risk of breast cancer in men, probably because of the conversion of testosterone to estrogen by aromatase in adipose tissue. There was also an indication of raised risk for the lowest BMIs.

6. Weight change is an independent risk factor (as it is in women).

7. Risk of breast cancer was statistically significantly associated with male-origin infertility. Risk was statistically significantly raised for men who had not fathered any children.

The publication of these findings has benefited public health by:

Enabling doctors to identify those at high risk who could benefit from targeted interventions.