20 February 2017

Present

TMG Members

Professor Julietta Patnick (Chair)

Ms Krys Baker

Professor Dame Valerie Beral

Dr Lucy Carpenter

Mrs Jacquie Jenkins (via conference phone)

Ms Kath Moser

Dr Hongchao Pan

Professor Sir Richard Peto

Professor Malcolm Reed Mr Keith Shaw

DMEC Members

Professor Janet Darbyshire (chair of DMEC)

Dr Ros Given-Wilson

Professor Gillian Reeves

Ms Jenny Rusby

Apologies

Professor Kevin Fenton

Professor Sir Mike Richards

Mrs Claire Borrelli

Professor Iain Lyburn

Professor Tom Meade

1. Welcome and Introductions

Apologies were received from Prof Kevin Fenton (KF), Prof Sir Mike Richards (MR), Mrs Claire Borrelli (CB), Professor Iain Lyburn (IL) and Tom Meade. It was noted that Margot Wheaton had retired.

2. Minutes of the last meeting (11^th Jan 2016) and matters arising

The minutes of the last meeting were accepted as an accurate record.

Matters arising:

Action points:

JJ explained that the new budget showed an overall reduction as 9 BSUs who were not part of the trial but were inviting all women 47-49 had been asked to stop inviting these women from Dec 2016. This released money which in due course could be put towards inviting some trial women 74+. For screening JJ said it was unlikely to be possible to start inviting women 74+ until 2018, possibly slightly earlier i f IT issues could be sorted. VB explained that the trial has ethical and CAG approval to add two follow up screening invites at 74-76yrs and 77-79yrs in the women randomised in aged 71-73. We are waiting for an IT program to be written and for a review of capacity in Breast Screening Units (BSUs). This would be piloted first in one or two centres in the next 12 months or so.

VB reported on self-referrals. The self-referral rate among women aged 47-49 randomised not to be screened is 0.9%, whereas among women aged 71-73 it is about 10%. As there were so many women not invited at 71-73 who self-referred, the degree of contamination could be greater than anticipated following the pilot and greater numbers of women to be randomised could consequently be required. RGW reported that previous trials had encouraged women over 70 to self-refer for breast screening. JJ also reported that PHE does encourage women to return for breast screening in their 70s despite there being little evidence in support of this.

There was some discussion on how this number could be minimised. RP said that it gave a greater case for recruiting as many over 70 women as possible to increase numbers.

Action: Discuss with PHE the inconsistency in their approach to women over 70.

Action: Start inviting those aged 74-76 ASAP. Look at BSUs that have a high self-referral rate.

It was noted that the meeting held in the Richard Doll Building in Oxford in September 2016 for representatives from Breast Screening Units (BSUs) had been well received and had a good attendance from BSUs.

3. Mid-year update

TMG members found the mid-year newsletter useful. A similar communication will be sent to TMG and DMEC members in 2017.

Action: JP/KB Send mid-year newsletter to TMG and DMEC members later in 2017

4. Updated Protocol with recent Amendment

Amendment 4.0 approved Sept 2016 included an:

Updated protocol to include option for two extra breast screening invitations in 74-79 age group, reference to the trial as “AgeX” in the protocol’s title, text, and descriptive material, revision of the Introduction and Background to bring them up to date.

Updated patient Information sheet which include changes to reflect possibly inviting women for screening throughout their 70s, ask women to let their screening office know if they are unable to attend their appointment, mention that record linkage to routinely collected NHS data will use data from NHS Digital (previously HSCIC),following a request from NHS Digital that this be mentioned. There was some discussion to clarify the intended exclusion from analyses of women who had had previous breast disease or breast surgery. It was agreed that the types of previous breast disease and of previous breast surgery would be looked at when relevant hospital data were available.

It was also agreed that the implementation of the extra screens should be carried out paying attention to a shortage of workforce within the BSUs.

Action: Discuss types of previous breast disease at next TMG meeting when relevant data are available.

5. External review

A document was circulated containing all data sources. The study has recently had approval from NHS Digital for the provision of hospital admissions data (HES) data earlier this year. HES records for 2.5 million women will be provided this spring/summer. Other data sources include PHE for screening data, cancer outcomes data and cancer screening history. ONS provide mortality and incident cancer data via NHS Digital.

Public Health England (PHE) have recently asked for an independent external review of the AgeX trial to be carried out, and a letter describing the results of the review was circulated to members. The anonymous reviewers wrote a strongly favourable report in support of the trial with an average score of 9.3 out of 10. The reviewers asked for a clarification of a couple of points. The TMG discussed response to the reviewers proposed by RP. It was agreed to clarify some of the responses and give more succinct replies to the questions and send our response to PHE.

Action: RP to edit our response to PHE and send it to them.

6. Plans for inviting women 74-79

2016 Summary of European Commission Recommendations on Breast Cancer Screening was circulated. They conditionally recommend screening for women 70- 74. The fact that there is no evidence for recommending this gives good grounds for supporting the trial.

RP stated that the EBCTCG was currently undertaking a review of individual data from all previous trials of breast screening; results should be available by 2018.

7. Trial update

As at the end of December 2016:

• 65 breast screening units are randomising
• 2,933,000 women are estimated to have been randomised to date
• 1,873,000 aged 47-49
• 1,060,000 aged 71-73
• the number of women randomised is increasing by an estimated 45,300 per month
• 29,000 aged 47-49
• 16,400 aged 71-73
• Almost all mammography now digital
• Inner city BSUs tend to have lower uptake 

8. Any other business

RGW reported a concern regarding a shortage of Radiographers and Radiologists which may have an impact on the trial that was expressed at the British Society of Breast Radiology meeting in Nov 2016. VB was attending a meeting of Breast Screening Radiologists on the 23^rd February 2017. It was suggested that the investigators describe the trial at scientific meetings.

Action: Trial needs to be actively communicating with BSUs in order to explain its rationale and importance, as was done in the early years of the trial. In particular present information about AgeX at scientific meetings.

Action: Need to start pilots for adding screening invitations 74+