Abstract P1-14-11: Assessing Prognosis and Therapy Response in Primary Systemic Therapy of Breast Cancer with Magnetic Resonance Spectroscopy
Authors: Bolan PJ , Wey A , Eberly LE , Nelson MT , Haddad TC , Yee D , Garwood M 
Published: August 2014

Abstract
PURPOSE: We have previously reported results of a pilot study in patients with locally advanced breast cancer receiving primary systemic chemotherapy (PST) showing that a decrease in tumor choline concentration ([tCho]) measured one day after starting treatment was associated with clinical response based on MRI. In this follow-up study with a larger cohort, we assessed whether early changes in [tCho] were associated with clinical response, based on both MRI and pathology, and survival.
METHODS AND MATERIALS: Women with locally advanced breast cancer scheduled for PST were scanned using a high-field MRI/MRS protocol prior to treatment, day 1 after treatment, and at the end of the first course of chemotherapy. MRI/MRS was performed on a 4 T Varian system with unilateral transmit/receive breast coils. MRI consisted of contrast-enhanced T1-weighted 3D gradient echo scans with one-minute temporal resolution. A single-voxel MR spectrum was acquired from the index lesion after MRI, and the concentration of total choline compounds ([tCho]) was quantified using water as an internal reference. Clinical response was assessed using RECIST criteria for measuring the longest diameter (LD) of the index lesion, and by pathologic complete response (pCR) at definitive surgery. Overall survival (OS) and invasive disease free survival (IDFS) were assessed by retrospective review of clinical records and the social security death index. The associations of change in [tCho] with pCR/LD response and with IDFS/OS were assessed using logistic/Cox regression, respectively, adjusted for node positivity and pCR status.
RESULTS: Of the 74 women enrolled in the trial, 51 women (ages 28–71, median 47 years) were scanned at all time points and included in the final analysis. Of these, 17 subjects had a partial or complete imaging RECIST response based on a ≥30% decrease of the LD of the index lesion. Pathologic complete response, defined as no detectable invasive disease in the breast, was observed in 13/51 overall subjects and in 6/35 hormone receptor positive (ER+ or PR+) subjects. Median follow-up time for survival analysis was 64 months (range 11–102 months). Linear models showed no significant association between change in [tCho] and either pCR or RECIST response. An increase in [tCho] between the pretreatment scan and day 1 after treatment was found to be associated with reduced likelihood of both OS and IDFS. We found no association between pCR status and either OS or IDFS when considering all subjects and in the HR+ cohort (see Table 1). No results could be reported for the HR- group (14 subjects) due to an insufficient number of events.

CONCLUSION: Compared to our previous study, we did not confirm that changes in [tCho] were associated with RECIST responses. However, increased MRS-measured [tCho] after 1 day of treatment was associated with reduced OS and IDFS independent of pCR. We conclude that increases in [tCho] might be a negative predictor of chemotherapy benefit.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-11.