Automated Low Dose Risk Assessment Mammography (ALDRAM)
Condition: Breast Cancer
Study type: Interventional

Summary: 
      Breast cancer (BC) is the commonest cause of death in young women. Breast screening in women
      aged 35-45, at increased risk due to their family history, has been shown to improve
      survival. However, 80% of women who develop BC do not have a family history. Numerous studies
      have shown that high mammographic density (MD) is one of the strongest risk factors for BC
      development. Full field digital mammography (FFDM) can be used to assess MD, however it is
      not recommended for population BC screening in those <40 years of age due to the concerns
      about the use of ionising radiation. Safe and accurate high throughput methods to quantify MD
      in young women are thus required to improve risk prediction and reduce BC mortality. This
      study aims to develop a low dose mammogram, with quantification of density using artificial
      intelligence, to facilitate high throughput risk assessment in young women. 600 women aged
      30-45, previously identified as being at increased risk of BC and attending for annual
      mammography at The Nightingale Centre will be recruited. Participants will undergo FFDM of
      the right breast as usual, however, following acquisition of the craniocaudal (CC) view, the
      breast will remain compressed and the mammogram dose reduced by 90% to deliver a LD
      mammogram. This process will be repeated for the right medio-lateral oblique (MLO) view. The
      left breast FFDM will proceed as normal. It is estimated that each extra exposure will take
      1-2 minutes only. Deep machine learning methods will be used to define the relationship
      between standard FFDM views and their low dose counterparts and determine which view (CC vs
      MLO) provides the best correlation to be taken forward to the next stage of the research.
    

Detailed description: 
      The more prolonged compression of the breast required to acquire the LD images may cause some
      additional breast discomfort. However, in a similar study in The Netherlands only 1% of women
      could not tolerate the procedure.

      Participants will receive an extra dose of ionising radiation amounting to 20% of the
      radiation dose of a single FFDM view (of which 4 are usually taken, 2 on each breast). The
      risks associated with this are described in section B and entered into the PIS.

      The research question for this study is whether an automated, low dose mammogram can be
      developed to provide an accurate assessment of mammographic density, and thus breast cancer
      risk, in women aged 30-45.

      The two key objectives are:

        1. To develop machine learning methods for automated quantification of mammographic density
           using low dose mammograms in a study of 600 women attending for annual Full Field
           Digital Mammography (FFDM).

        2. To validate Automated Low Dose Risk Assessment Mammography (ALDRAM) against automated
           FFDM assessment that has been shown to predict BC risk.

      Breast cancer is the commonest of all causes of death in young women. Currently the only
      factor triggering referral to risk assessment clinics is the presence of a family history.
      Although this is known to confer increased risk, only 20% of young women who develop BC
      actually have such a family history of the disease. Thus 80% of cases come 'out of the blue'
      and methods to assess risk in the general population are required if we are to improve
      survival (screening in those at increased risk aged 35-45 has been shown to reduce
      mortality). High mammographic density has been shown in multiple studies to confer
      significantly increased risk of BC, however population screening with full field digital
      mammograms is not recommended in those <40 primarily due to the reduced sensitivity and use
      of a moderate doses of ionising radiation. There is thus an urgent need for safe, high
      throughput, techniques to accurately define mammographic density in young women - the purpose
      of this study. Following consent and initial Case Report Form (CRF) completion, mammography
      will commence as standard. The right breast craniocaudal (CC) view will be performed first
      and the steps below followed:

        1. The breast will be positioned as standard for the CC view.

        2. The Automatic Optimisation of Parameters (AOP; also known as Automatic Exposure Control
           (AEC)) will be performed for target, filter, Peak KiloVoltage (kVp) and MilliAmpere
           second (mAs) selection for Full Field Digital Mammography (FFDM).

        3. The full field CC view will be performed as standard.

        4. The breast will remain compressed whilst the radiographer manually reduces the mAs by
           90% or to the minimum value of 4 mAs (the machine does not deliver less than 4 mAs). No
           other parameters will be changed. A repeat CC exposure at this reduced dose will be
           performed.

        5. The machine will be reset to automatic and the subsequent mediolateral oblique (MLO)
           view will be obtained and the low dose view performed again as above.

        6. The left breast CC and MLO views will then be obtained as standard.

        7. This concludes the woman's participation in the study. The images from the low dose and
           FFDMs will then be processed to determine whether mammographic density from low dose
           mammograms correlates with that from FFDM and what modifications are required to
           automated algorithms for future studies.
    

Intervention name(s): Low dose mammogram
Intervention type(s): Radiation
Intervention description(s): Low dose mammogram
Intervention model: Single Group Assignment
Intervention model description: The research question for this study is whether an automated, low dose mammogram can be developed to provide an accurate assessment of mammographic density, and thus breast cancer risk, in women aged 30-45.
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Low dose mammogram