SPectroscopic Assessment of Chemotherapy Efficacy in breast cancer patients

Neoadjuvant chemotherapy (NAC) before surgery is used in patients with
aggressive breast cancer to reduce tumor volume and the risk of distant
metastases. Unfortunately, the effect of neoadjuvant chemotherapy can only be
assessed in a late phase of the therapy. Therefore, in case of an ineffective
therapy, patients already suffered from the side effects of chemotherapy
without any benefit. Currently, no good non-invasive method capable of
assessing the efficacy of chemotherapy before the surgery is available. By
using new non-invasive magnetic resonance imaging techniques we are able to
evaluate tumor metabolism (by means of 31P-magnetic resonance spectroscopy
(31P-MRS)). An ongoing feasibility study already showed differences in five
patients when the biomarkers are measured before and halfway the chemotherapy
(11-146 / NL36429.041.11). To validate this biomarker to predict the response
to NAC, more patients are needed. Furthermore, we are able to evaluate
indirectly the vascularity (dynamic contrast-enhanced magnetic resonance
imaging (with DCE-MRI)), cell density (with diffusion weighted imaging (DWI))
and the chemical exchange (with chemical exchange saturation transfer
(CEST-MRI)). If we are able to prove that biomarkers based on MRI measurements
that are assessed at the start of chemotherapy are able to select patients that
will not respond to therapy, we can prevent those patients from receiving more
of the ineffective neoadjuvant chemotherapy. The patient will not have to
endure the side effects of ineffective neoadjuvant chemotherapy, which have a
large impact on the quality of life of the patient and her direct environment.
Applying metabolic imaging will be a step ahead towards personalized cancer
care. It will provide more detailed information about the cancer, enabling
tuning of the therapy to the individual patient. If this method works in this
group of breast cancer patients it can be transferred to patients with other
types of cancer who receive neoadjuvant chemotherapy. Moreover, a non-invasive
method to assess metabolic changes directly in the cancer will also speed up
development of new systemic therapies as its effects can be assessed in an
early stage.

First, the threshold for the biomarkers of 31P-MRS will be determined. These
biomarkers can indicate whether a patient with breast cancer benefit from the
neoadjuvant chemotherapy (NAC). Then it is determined whether a (combination
of) biomarker(s) of DCE-MRI, DWI and CEST-MRI with and without 31P-MRS, also
leads to a threshold value that indicates whether a patient with breast cancer
will benefit from the NAC.

Prospective cohort study.

Subjects do not directly benefit from participation. Ultimately, in case of a
positive outcome, future patients may benefit from a 7 Tesla (T) MRI scan. The
added risks of study participation are considered negligible. Standardized 7T
MRI checklists will be in effect to ensure MRI safety. The burden for the
patient includes the time the patient will spend for making the extra 7T MRI
scans. Patients will be compensated for travel costs because of the extra
visits to the hospital for making the 7T MRI scan. Treatment of patients will
be based on the standard, evidence based, medical care and will not be
influenced by the DWI, CEST or 31P-MRS results of the 7T MRI scans or the
assessments of the pathological marker for tumor proliferation (Ki-67).