Clinical evaluation of 4D Breast Imaging for Personalized Breast Cancer Treatment

After breast cancer diagnosis, staging and characterization are performed to
determine optimal local and/or systemic treatment. When possible, breast
conserving therapy is used. To make breast conserving therapy possible,
neoadjuvant therapy (NAT) is used to reduce tumor size. Achieving
pathologically complete response (pCR) during NAT is associated with improved
outcomes and survival rates, especially in patients with the most aggressive
malignancies, but currently only up to 40% of NATs result in pCR.
Variability in NAT response may be due to tumors being heterogeneous and
therefore treatment being based on the most prominent, e.g., molecular profile,
may fail to target other, molecularly distinct, areas of the tumor. This
non-uniform NAT response leads to non-pCR, associated with poorer outcomes.
Furthermore, during NAT, response is not closely monitored, so the treatment is
not adjusted even though the tumor may be progressing, may have never responded
or stopped responding, or has already completely responded close and accurate
monitoring of early treatment response will allow for flexibility in therapy,
maximizing the possibility of cure.
Finally, if pCR was not achieved or cannot be assured, accurate assessment of
the remaining tumor extent is important to optimize surgical plans. An optimal
surgical plan, developed also taken into consideration the localization of in
situ vs. invasive disease, will minimize the need for re-excision while allow
for a more tissue-conserving surgery plan.
Clearly, there is evidence that advanced imaging could, and should, play an
important role in personalizing and optimizing NAT and breast conserving
therapy. We hypothesize that using four-dimensional dynamic contrast-enhanced
dedicated breast computed tomography (4D DCE-BCT) will result in the ability to
characterize sub-tumor habitats of different physiological and molecular nature
that respond differently to NAT, monitor and predict final response to NAT, and
help guide surgical plans, including avoiding surgery completely when pCR to
NAT is certain to have been achieved. Therefore, 4D DCE-BCT will have a very
significant impact on breast cancer treatment, resulting in an important
decrease in breast cancer mortality and morbidity.

Part A: Determine the performance of using 4D DCE-BCT for tumour staging.
Part B: Determine the performance of 4D DCE-BCT in monitoring of treatment
response and prediction of final treatment outcome based on early response in
patients that undergo NAT. Of special interest will be determining the ability
to predict pCR, to be able to obviate the need for surgical intervention.

Observational cohort study.

The research will not be directly beneficial to the subjects since the research
4D DCE-BCT results will not influence the subject*s treatment, if any. Patients
do also not have a direct disadvantage of participation, except for the small
risk associated with the additional x-ray dose for the 4D DCE-BCT acquisitions.
The mean glandular radiation dose to an average breast is ~15.0 mGy, which is a
low dose for post-diagnostic use on breast cancer patients who will either
undergo radiotherapeutic treatment (thousands of times higher dose) or
mastectomy. Successful completion of this project will have a high payoff with
a very significant impact on breast cancer treatment, resulting in an important
decrease in breast cancer mortality and morbidity