Abstract P2-03-01: Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer
Authors: Saraf Anurag , Tahir Ismail , Hu Bonnie , Dietrich Anna-Sophia , Tonnesen Paul Erik , Sharp Greg , Tillman Gayle , Fintelmann Florian , Jimenez Rachel 
Published: March 2023

Background Adjuvant endocrine therapy (ET) is standard of care in women with hormone receptor-positive (HR+) breast cancer (BC) with the goal to reduce recurrence. However, early discontinuation of ET occurs in 30-40% of women, largely attributable to toxicity, and leads to increased recurrence risk. There is considerable overlap in risk factors that predict toxicity from ET and chemotherapy, including age, co-morbidities, and geriatric conditions. Baseline low skeletal muscle area (SMA) on chest computed tomography (CT) is a surrogate marker for sarcopenia and predicts for significant toxicity and intolerance to chemotherapy in women with BC. No study has assessed the association of sarcopenia with toxicity-related discontinuation of ET in women with early-stage HR+ BC. Methods This single center retrospective cohort study included consecutive women with Stage 0-II HR+ BC who received ET and adjuvant radiotherapy (RT) from 01/2011-12/2017. Inclusion required a minimum of 5-year clinical follow-up after diagnosis. We used a validated deep learning pipeline to quantify SMA (cm2) at the tenth thoracic (T10) vertebral body on existing RT planning CT. The skeletal muscle index (SMI [cm2/m2] = SMA/(patient height (m))2) was calculated to adjust for patient height. Sarcopenia was defined as SMI&lt; 32.3 cm2/m2, based on a previously validated independent cohort of young healthy women. The primary endpoint was toxicity-related discontinuation of ET less than 60 months after initiation of ET. Secondary endpoints included any NCI CTCAE v5.0 Grade 3-5 toxicity from ET and ipsilateral breast tumor recurrence. We assessed associations between ET discontinuation and SMI (continuous), as well as thoracic sarcopenia (dichotomous), using logistic regression adjusting for baseline characteristics. We used cox proportional hazards regression to assess disease-free survival (DFS), defined as ipsilateral breast tumor recurrence, locoregional recurrence, or distant metastasis adjusting for baseline and treatment characteristics. Results A total of 265 women (median age 67 years) met inclusion criteria. The majority of women had a comorbidity index of 0-1 (89%) and were Caucasian (89%). The median follow-up was 82 months, 5-year overall survival was 96% and 5-year DFS was 94%. Diagnoses included DCIS (12%), IDC (76%), or ILC (12%); most were T1 (69%) or T2 (18%) and N0 (85%), ER-positive (100%), PR-positive (85%), or HER2-negative (9%). Most common ET type was anastrozole (63%), letrozole (16%), and tamoxifen (17%). SMI (continuous) was not associated with older age, Charlson Comorbidity Index (CCI), race, or tumor stage. A total of 64 (24%) women experienced toxicity-related early discontinuation of ET. On multivariate analysis (MVA), lower SMI was associated with increased toxicity-related early discontinuation of ET (Odds Ratio [OR] 0.89 per 1 cm2/m2 SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. Lower SMI was associated with higher risk of grade 3-5 toxicity from ET (OR 0.89 per 1 unit SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. On MVA, sarcopenia was associated with higher risk of toxicity-related early discontinuation of ET (OR 2.43, p=0.019). DFS was associated with toxicity-related early discontinuation of ET (HR 8.06, p=0.005), grade 3 histology (HR 1.42, p=0.042), and multifocal disease (HR 2.55, p=0.040), but not age, histology, stage, or lymphovascular invasion (p&gt;.05 for all). Conclusion Low baseline thoracic skeletal muscle is associated with toxicity-related early ET discontinuation in women with early-stage HR+ BC. Further studies should attempt to generalize this association to all HR+ BC who are candidates for ET. High-risk patients may be candidates for aggressive symptom management or alternative adjuvant therapies.

Citation Format: Anurag Saraf, Ismail Tahir, Bonnie Hu, Anna-Sophia Dietrich, Paul Erik Tonnesen, Greg Sharp, Gayle Tillman, Florian Fintelmann, Rachel Jimenez. Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-01.