The CAROLE (CArdiac Related Oncologic Late Effects) Study: A Phase II, single-arm feasibility trial.

Abstract

11569 Background: Long-term breast cancer survivors are at risk of late effects from cardiotoxic (tox) radiation (RT) and chemotherapy (chemo). However, there is a paucity of data to recommend appropriate cardiac screening for those ~10 years (yrs) after diagnosis (dx). This phase II, single arm study assessed multimodality screening in a heterogeneous cohort of long-term survivors. Methods: Our prospective, single center pilot study enrolled 201 (of 200 planned) eligible patients (pts): age 18-65 at dx, with treatment (tx) for breast cancer (any stage/tx) in 2004-2011 (≥6 yrs prior), with no cardiac disease (dz) at dx. The primary endpoint was presence of any cardiac dz (preclinical or clinical) on electrocardiogram (EKG), echocardiogram (echo), or coronary artery calcium CT (CAC CT); secondary endpoint included clinical (clin) dz alone. Subgroups assessed were: no tox chemo or RT (no tox), tox RT (left-sided) alone, tox chemo (anthracycline) alone, and both tox chemo and tox RT (tox chemoRT). Results: After enrollment (6/2017-7/2018), 200 pts had sufficient data for analysis. Median age was 50 (29-65) at dx, 63 (37-77) at imaging, and interval (dx to imaging) was 11.5 (6.7-14.5) yrs. There were 44% no tox, 31.5% tox RT, 16% tox chemo, and 8.5% tox chemoRT pts. Among all pts, 77.6% displayed evidence of any cardiac dz, 51.5% had clin dz. Per modality, rates of any and clin dz were: 27.1%/10% EKG, 50.0%/25.3% echo, and 50.8%/45.8% CAC CT. Among subgroups, these rates were: 73.9%/53.4% no tox, 82.5%/58% tox RT, 75%/38.7% tox chemo, and 82.4%/35.3% tox chemoRT (NS on χ2 test, p = .58/p = .15). Multivariable logistic regression with tox RT, tox chemo, and age as covariates, showed no significant tox RT (NS) or tox chemo effect (NS), however, increasing age was significantly associated with higher incidence of cardiac dz (p < 0.01; OR = 1.12 per yr, 95% CI: 1.07-1.18). Conclusions: Among pts with a median of > 10 yrs post breast cancer tx, multimodality CAROLE screening was feasible and showed high rates of cardiac dz (any/clin = 77.6%/51.5%) among all subgroups, including those without tox tx. This study provides evidence for long-term cardiac screening in a diverse group of breast cancer survivors and provides a novel pathway for evaluation. Clinical trial information: NCT03235427.

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative

“…These findings suggest that the choice of antihypertensive may be more important in cancer survivors than the general population in preventing cardiac events. Given what is known regarding cancer treatments' effects on the heart [11,38], nonsymptomatic cardiac changes resulting from a broad set of cancer treatments may leave women with underlying cardiovascular vulnerabilities (i.e., increased fibrosis due to radiation or a prothrombotic state due to targeted biologic agents) [11] that differ from their cancer-free peers. In this context, it is plausible that BB medications convey greater cardioprotection relative to ACEi/ARB in cancer survivors potentially owing to their mechanism of action rather than through BP control.…”