MRI study of long-term body composition alterations in HER2+ breast cancer survivors

Early breast cancer (EBC) remains the most common invasive cancer in North American women. With improvements in detection, systemic therapies and supportive care, long-term survival in early stage disease now approaches 90%. In EBC survivors, fat pool distribution, specifically visceral and intermuscular fat (IMF) is associated with increased cardiovascular disease risk regardless of pre-existing risk factors or cancer treatments. We previously showed that 1 year after trastuzumab initiation, visceral fat and IMF volumes increased significantly while muscle volume decreased in HER2+ EBC patients. However, the longer-term effects of such exposures on body composition remain unknown.

We hypothesized that over time, deleterious changes would progress with increasing fat and decreasing skeletal muscle in EBC patients exposed to trastuzumab-based chemotherapy.

A follow-up MRI study was conducted with prior participants of the MANTICORE (Multidisciplinary Approach to Novel Therapies In Cardio-Oncology REsearch) trial. Enrolment was limited to those without recurrent disease; 54 patients consented to participate. Eight scans were not included (tissues outside field of view, files unevaluable) thus 46 scans were included. The identical MRI protocol was used at all timepoints with five slices centered at the 3rd lumbar vertebra. Sum of volumes of muscle, IMF and visceral fat were measured using custom semi-automated software. Bones and organs were removed from the visceral fat pool. Repeated measures of ANOVA with appropriate post-hoc correction for multiple comparisons were performed at baseline, 3-month, 12-month, 24-month and 5 years.

Participants were 58.6 ± 8.6 years of age and median 5.5 years had elapsed since trastuzumab completion. All were living independently with no cardiac events occurring in the intervening years. Ten had initiated cardiometabolic pharmacotherapy (beta-blockade, ACEI/ARB, diuretic or diabetes). Muscle mass increased over the 5 years (main effect of time, p=0.002); however, was lower at 1 year versus 3 months (Fig 1A). IMF also increased over 5 years (main effect of time, p=0.005) but the pattern was different with increases observed as early as 3-months (Fig 1B). Visceral fat increased up to 2 years then plateaued (main effect of time, p= 0.038; Fig 1C).

To our knowledge, this is the first and longest prospective study assessing changes in body composition in EBC using MRI both during and years after trastuzumab-based chemotherapy. Our data suggests that there may be ‘targetable’ timepoints for interventions such as pharmacotherapy, nutrition and exercise-based rehabilitation aiming to improve the quality and quantity of life in EBC survivors.Figure 1