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Introduction: Aromatase Inhibitors (AI) are a mainstay of treatment for hormone receptor positive breast cancer (BC) in postmenopausal women. However, patients under AI treatment often suffer from Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS), defined as myalgias, arthralgias, or joint stiffness in hands, fingers, knees, hips and feet, which may limit treatment and subsequently increase BC mortality. The depletion of estrogen following AI initiation has been postulated to cause AIMSS. However, it has not yet been fully established about the clinical significance of AIMSS and its risk factors and the underlying mechanisms. The aim of this study is to identify epidemiologic risk factors associated with the development of AIMSS in BC patients on adjuvant AI therapy. Methods: We conducted a retrospective review of medical records among 111 stages 0-III hormone receptor positive BC patients who received adjuvant AI therapy, including anastrozole, letrozole or exemestane, between January 2009 and June 2017, at the University of Maryland Greenebaum Comprehensive Cancer Center. To be eligible, women had to be either postmenopausal or premenopausal, on a GnRH analog for at least 3 months, and report of no AIMSS before the AI initiation. We collected patients’ data on demographics, lifestyle factors, reproductive histories, tumor characteristics, types of AI and cancer treatment, co-morbidities, use of medications, length of AI therapy, and onset and severity of AIMSS. We defined severe AIMSS as AIMSS requiring the change of AI therapy or discontinuation of AI. The demographics and clinicopathological characteristics of patients on AI therapy and frequencies of AIMSS onset during AI treatment was characterized with means (SDs) or percentages. To estimate the association of severe AIMSS with epidemiologic risk factors, odds ratios (ORs) and 95% confidence intervals were calculated using multivariable-adjusted logistic regression. Results: This study included 111 BC patients with a mean age of 64 years. Their mean BMI at time of BC diagnosis was 30.8 kg/m2, and 41% of patients were White, 39% were Black, 4% were Asian/Pacific Islander, and 16% were other. Majority of patients (77%) had no prior experience of tamoxifen use and used letrozole as an initial AI therapy (70.3%); 15.3% used anastrozole, and 14.4% used exemestane. We found that 52.6% of patients experienced any degree of AIMSS while on AI therapy. In particular, 19.8% of patients required change or holding AI therapy, and 3.6% permanently discontinued AI because of AIMSS. We observed that older age at AI therapy initiation and higher levels of circulating vitamin D-25OH were significantly associated with lower odds of severe AIMSS. Multivariate ORs (95% Cis) comparing the highest to the lowest tertile of age and vitamin D levels at AI initiation were 0.18 (0.05-0.71) and 0.10 (0.02-0.49), respectively (all P-trend: ≤ 0.04). There were no significant association between race, body mass index, smoking, alcohol use, reproductive factors, type of AI therapy, and tamoxifen use prior to AI therapy. Conclusions: In our study, nearly 52.6% of BC patients on adjuvant AI therapy experienced AIMSS. Of those, 23.4% changed or discontinued AI regimen due to severe AIMSS. Older age and higher circulating levels of vitamin D-25OH at the initiation of adjuvant AI therapy were associated with lower risk of developing severe AIMSS. The study results support the clinical significance of AIMSS in BC patients leading to decreased adherence to AI therapy. The replication of our association with age and vitamin D levels in a larger study is warranted as it may provide a greater insight into etiologies of AIMSS. Citation Format: Yamin Sun, Simran Elder, Seungyoun Jung, Candace Mainor, Shruti Murali, Paula Rosenblatt, Katherine Tkaczuk. Factors associated with aromatase inhibitor associated musculoskeletal symptoms in early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-13.

525 Background: Hormone receptor positive (HR+) breast cancer comprises the largest subgroup of breast cancer. Aromatase Inhibitors (AI) are a key treatment for HR+ BC patients (pts) and reduce mortality. Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS), defined as myalgias, arthralgias, or joint stiffness, occur in up to 50% of pts leading to low adherence to and often discontinuation of therapy. Little is known of the mechanism of AIMSS or its predisposing risk factors. This study aims to identify risk factors associated with AIMSS development in BC patients on AI therapy. Methods: We conducted a medical record review of pts with non-metastatic HR+ BC on adjuvant AI therapy between January 2009 and June 2017 at the University of Maryland Comprehensive Cancer Center. This study included 194 ptswho were free of arthralgia prior to AI therapy. We analyzed pts’ demographics, lifestyle factors, reproductive history, tumor characteristics, medications, cancer treatment, co-morbidities, AI type, onset and severity of AIMSS. Severe AIMSS was defined as requiring change in AI therapy or discontinuation. Multivariable-adjusted logistic regression was used to identify risk factors for severe AIMSS. Results: The mean age of participants was 61. The mean BMI at diagnosis was 30 kg/m2. 41% of pts were White, 40% were Black, 7% other and 12% unknown. Most (79%) did not have a history of tamoxifen and 16% were on GnRH agonists. Most (71%) used letrozole as initial AI therapy; 18% anastrozole; and 11% exemestane. 56% experienced AIMSS while on AI therapy and 20% required change or hold of AI therapy. 4% permanently discontinued AI due to AIMSS severity. BMI at diagnosis was significantly positively associated with risk of AIMSS. Multivariate odds ratio (95% confidence intervals) comparing the highest to lowest tertile of body mass index (BMI) at diagnosis was 4.01 (1.07-10.90; Ptrend: 0.05). There were no significant associations with race, smoking, reproductive factors, type of AI therapy, tamoxifen use prior to AI therapy, medication use, experience of other cancer treatments, and tumor characteristics. Conclusions: 56% of BC pts on adjuvant AI therapy experienced AIMSS. 24% of these changed, held or discontinued AI regimen due to severe AIMSS. Higher BMI at diagnosis was associated with a higher risk of AIMSS. Our results confirm clinical significance of AIMSS among BC pts on AI therapy and suggest BMI as a modifiable factor for AIMSS. A larger study is warranted to replicate our findings and seek other possible risk factors for AIMSS.

Cholangiocarcinoma (CCA) is an uncommon cancer and accounts only for 3% of all gastrointestinal malignancies. In this report, we present a case of an intrahepatic cholangiocarcinoma masquerading as acute fatty liver of pregnancy (AFLP). A 38-year-old female who is 36-week pregnant presented with a 1-week history of headache, nausea, vomiting, and right upper abdominal pain, along with hepatomegaly. Laboratory investigations were remarkable for mild leukocytosis, hyperbilirubinemia, proteinuria, and elevated transaminases and prothrombin time. Ultrasound of the liver revealed hepatomegaly, fatty infiltration, and a right hepatic lobe mass. Based on the overall picture, AFLP was suspected, and the patient underwent delivery by Cesarean section. However, bilirubin and liver enzyme levels gradually increased after delivery. MRI revealed a large dominant hepatic mass along with multiple satellite lesions in both lobes. Biopsy revealed the presence of intrahepatic CCA. CCA presenting during pregnancy is extremely rare with only 9 other cases reported in the literature. Therefore, the signs and symptoms can be easily confused with other more common disorders that occur during pregnancy.

Introduction The "POEMS" Syndrome, defined by its hallmark features of polyneuropathy, organomagaly, endocrinopathy, monoclonal plasma cell proliferative disorder, and skin changes has long been an enigma in terms of diagnosis and treatment. In recent years, clinicians and researchers have attempted to clarify diagnostic criteria. It is known that "VEGF," vascular endothelial growth factor, plays a large role in the pathophysiology of this disease.1Most recently, Angela Dispenzieri proposed a set of diagnostic criteria, which were published in the American Journal of Hematology.2We applied this suggested diagnostic criteria retrospectively to patients in our institution who carried a diagnosis of POEMS Syndrome. Additionally, we recorded the VEGF of these patients and their outcomes. Methods The.medical record was queried for patients with POEMS diagnosed in the last 5 years. A total of 16 patients met criteria. The primary outcome was to determine the percentage of patients who met the criteria proposed by Dispenzieri. A secondary outcome was to determine, in those patients who did not meet the criteria, the reason that they were not met. Another secondary outcome was to determine the percentage of patients who were alive or deceased. The criteria proposed by Dispenzieri (Table 1) were applied to each patient to assess whether they were met. If the diagnostic criteria were not met, the reason as to why they were not was recorded. Each patient outcome of "alive," "deceased," or "unknown" was recorded. Results Of the 16 patients analyzed, 14 (88%) had enough information to be included. Of these 14 patients, nine (64%) met the criteria proposed by Dispenzieri. Of the five patients that did not meet the criteria, four (80%) did not meet them due to the lack of a presence of a major criteria. One patient of the five (20%) that did not meet the criteria did not have the mandatory finding of polyneuropathy. VEGF levels ranged from 26-9504pg/mL, with an average of 1190pg/mL. The range for the patients who met the diagnostic criteria proposed by Dispenzieri was 1755pg/mL. Of our total patient population analyzed, 10 out of 14 patients (72%) were alive at time of retrospective review, including six out of nine (66%) that met the diagnostic criteria. Two out of 14 patients (14%) were found on review to be deceased, including one out of the nine (11%) that met the diagnostic criteria. Two out of 14 patients (14%) were determined to be "unknown" if alive or deceased, both of whom met the diagnostic criteria. Discussion Patients with POEMS syndrome often experience a delay in diagnosis due to the rarity of the disease as well as a lack of high index of suspicion for the condition in many cases. Additionally, POEMS syndrome is often mislabeled as another neuropathic condition. Efforts have been made to establish a standard criteria for diagnosis. We applied the criteria proposed by Dispenzieri this year in the American Journal of Hematology. In our retrospective study, we found that that 64% of our patients who carried a diagnosis of POEMS syndrome met the criteria for POEMS diagnosis using these proposed criteria. We found that the most common reason for not meeting the criteria in our patient population was the lack of a major criterion. Major criteria (Table 1) include Castleman Disease, sclerotic bone lesions and VEGF elevation, one of which must be met to receive a diagnosis of POEMS syndrome. Additionally, one of our patients did not meet the criteria due to the lack of the mandatory finding of polyneuropathy. The average VEGF levels in our patients were 1190pg/mL, but were higher at 1755pg/mL in the cohort who met the diagnostic criteria. 72% of our total patients were alive at time of review, including 66% of the patients who met the diagnostic criteria. We conclude that the criteria proposed by Dispenzieri provide a concise guideline to identify patients with POEMS syndrome. These criteria are simple to apply, and would potentially help to increase the index of suspicion and earlier diagnosis of patients with POEMS syndrome. This would be expected to lead to earlier initiation of therapy. Additionally, this analysis supports previous studies that show that VEGF levels are correlated with disease activity and that overall prognosis for patients with POEMS syndrome is favorable. Disclosures No relevant conflicts of interest to declare.