Abstract PS13-02: Global myocardial perfusion is reduced in premenopausal breast cancer patients treated with ovarian function suppression and aromatase inhibitor therapy: An adenosine stress T1 map CMR study
Authors: Thomas Alexandra , D'Agostino Ralph B. , Ansley Katherine C. , Park Sung , Kotak Anuj , Sorscher Steven M. , Melin Susan , Douglas Emily H. , Vasu Sujethra , Romitti Paul A. , Hundley William G. , Jordan Jennifer H. 
Published: February 2021

Introduction: Premenopausal women with high-risk hormone receptor-positive (HR+) breast cancer (BC) undergo abrupt menopause induction with aromatase inhibitor (AI) anti-estrogen therapy and ovarian function suppression (OFS). This treatment improves recurrence-free survival but may increase cardiovascular (CV) risk associated with early hypoestrogenemia as observed in women with non-cancerous reasons for early loss of ovarian function. We sought to identify if OFS+AI therapy is associated with myocardial perfusion changes, a subclinical marker of coronary heart disease. Methods: We evaluated women with paired adenosine cardiovascular magnetic resonance imaging scans at 3-to 6-month intervals using cines and T1 maps in standard short-axis planes. As increased blood flow from vasodilation increases adenosine stress parametric T1 values of the myocardial tissue, the myocardial perfusion reactivity was calculated from the percent increase of stress versus native (pre-stress) T1 maps. Double-blinded post-processing of images was performed in CircleCVI software. Statistical analyses were performed in MATLAB (p&lt;0.05 defined as statistically significant) using paired t-tests for within-group comparisons and two-sample t-tests for between-group comparisons. Results: Twenty-one premenopausal women (16 Caucasian, 5 African American; median age 44.7 years) were accrued in 16 months - 14 with HR+ BC within 3 years of initiating OFS+AI (median 8 months) and 7 with triple negative BC within 3 years of chemotherapy (median 10 months) for comparators. Global myocardial perfusion reactivity to adenosine stress declined in HR+ women on OFS+AI therapy during the 3-6 month study interval (-1.3%; 95%CI: -3.4-0.7%) which was significantly different (p=0.02) from changes observed in comparators who had an improvement in perfusion during the interval (3.2%; 95%CI: -1.2-7.6%) (Table). Left ventricular (LV) function remained unchanged during the 3-6 month interval for all groups (p&gt;0.05). The cardiovascular stress tests identified two HR+ women (14%) with abnormal results during stress imaging who were sent for further cardiovascular evaluations.Conclusions: Women with HR+ BC treated with OFS+AI exhibited a decline in global microcirculatory perfusion during an adenosine cardiac stress test with normal LV functional parameters. Alternatively, triple negative BC patients trended to have an improvement in LV function during the interval with non-significant improvement in myocardial perfusion. This study demonstrates a decline in myocardial perfusion in premenopausal women on OFS+AI therapy, suggesting subclinical coronary artery effects due to early hypoestrogenemia. Future work should confirm these results, identify women at higher risk, and test strategies to mitigate cardiotoxicity in premenopausal women with HR+ BC.

Table: Cardiovascular magnetic resonance (CMR) study measures for HR+ BC patients on OFS+ AI therapy and triple negative BC patientsCMR MeasureHormone Receptor-Positive Breast Cancer(n=14)Triple Negative Breast Cancer(n=7)p-value for difference in change by groupBaselineFollow-upp-valueBaselineFollow-upp-valueLV Ejection Fraction, %56 (51, 61)56 (51, 62)0.8255 (50, 60)60 (55, 65)0.060.12EDVindex, mL/m270.6 (63.7, 77.5)69.9 (63.5, 76.3)0.7365.2 (58.0, 72.3)66.8 (51.4, 82.1)0.740.60ESVindex, mL/m231.3 (26.2, 36.5)30.4 (26.2, 34.5)0.3729.4 (23.8, 35.0)27.1 (19.4, 34.8)0.360.55SVindex, mL/m239.3 (34.3, 44.2)39.5 (33.9, 45.1)0.9035.8 (32.3, 39.3)39.7 (31.2, 48.2)0.230.29Myocardial mass index, g/m248.1 (42.7, 53.6)44.6 (40.0, 49.3)0.0843.5 (40.2, 46.8)41.0 (33.3, 48.7)0.420.77Global myocardial perfusion reactivity, %2.8 (1.1, 4.4)1.4 (-0.4, 3.3)0.191.4 (-0.9, 3.7)4.6 (0.9, 8.4)0.130.02Basal SAX myocardial perfusion reactivity, %2.2 (0.7, 3.7)1.4 (0.3, 2.5)0.261.8 (0.2, 3.4)2.1 (-1.7, 5.9)0.850.46Mid SAX myocardial perfusion reactivity, %2.4 (-.3, 5.2)0.5 (-1.5, 2.7)0.221.2 (-1.9, 4.2)3.3 (-0.9, 7.6)0.360.12Apical SAX myocardial perfusion reactivity, %3.4 (1.2, 5.7)2.1 (-1.4, 5.7)0.490.8 (-2.6, 4.1)8.8 (3.7, 13.9)&lt;0.05&lt;0.01LV = left ventricular, EDV = end diastolic volume, ESV = end systolic volume, SV = stroke volume, SAX = short-axis slice; volumetric and mass measures indexed to body surface area. Data are presented as mean (95% Confidence Interval).

Citation Format: Alexandra Thomas, Ralph B. D'Agostino, Jr., Katherine C. Ansley, Sung Park, Anuj Kotak, Steven M. Sorscher, Susan Melin, Emily H. Douglas, Sujethra Vasu, Paul A. Romitti, William G. Hundley, Jennifer H. Jordan. Global myocardial perfusion is reduced in premenopausal breast cancer patients treated with ovarian function suppression and aromatase inhibitor therapy: An adenosine stress T1 map CMR study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-02.