Abstract P2-08-11: High prevalence and incidence of new onset diabetes in metastatic breast cancer
Authors: Ballinger Tarah , El-Azab Sarah , Liu Ziyue , Guise Theresa , Imel Erik 
Published: March 2020

Abstract
Background: The association between pre-existing diabetes mellitus (DM) and subsequent increased incidence of breast cancer (BC), as well as worse survival after BC diagnosis, is well described. However, the reverse relationship of BC or metastases to development of new onset DM is unknown. Preclinical evidence suggests that increased bone destruction due to bone metastases or endocrine therapy impairs insulin secretion via TGFβ-mediated oxidation of the ryanodine receptor in pancreatic β- cells, predisposing patients to development of new onset DM. This analysis describes the prevalence and new onset of DM in metastatic BC compared to matched, unaffected controls and non-metastatic BC.
Methods: This retrospective study collected data on women from the Indiana Network for Patient Care (INPC, a multi-health system electronic health record data warehouse), and the Indiana State Department of Health Cancer Registry from 2015 to 2017. Diagnosis of BC and metastases were established using ICD codes from INPC and confirmed in the cancer registry. DM was defined using a combination of ICD codes, diabetic medication prescriptions, and hemoglobin A1c &gt;6.5%. Controls without BC were matched to all BC cases by birth year and race. The prevalence of DM before, or &lt; 30 days after, BC diagnosis is described for non- cancer controls, all patients with BC, and subgroups without metastases, any metastases, and with bone metastases. In patients without evidence of DM prior to or &lt; 30 days after BC diagnosis, the incidence of new onset DM was compared to matched controls over the same time period. The occurrence of new DM was evaluated both including and excluding the first 6 months after BC diagnosis to account for potential DM diagnosis simply due to medical attention. Prevalence and subsequent incidence of DM was compared between cases and controls using Pearson’s chi-square tests. Variables including demographics, comorbidities, BC treatment, A1c values, and DM treatments were also collected.
Results: Any DM diagnosis, pre-existing DM, and new onset DM were higher in breast cancer cases compared to controls (Table). While pre-existing DM was similar between those with metastatic and non-metastatic DM (35.0% vs. 32.2%, p=0.22), new onset DM was higher in metastatic disease compared to non-metastatic BC (14.4% vs. 7.0%, p&lt;0.001). Hemoglobin A1c was higher in those with metastatic disease, particularly those with bone metastases (8.8 vs 7.5, p&lt;0.001).
Conclusions: Diabetes is highly prevalent in this Indiana BC cohort. Incidence of new onset DM after BC is higher in those with metastatic BC compared to both controls and BC cases without metastatic disease. Hemoglobin A1c was highest in those with bone metastases, further supporting the hypothesis that bone turnover may influence insulin secretion and glucose metabolism. Additional investigation will analyze the influence of medications (chemo-, endocrine, and bone protective therapy) on development of DM. As more patients live longer with metastatic BC, identification and management of DM will be imperative given its impact on BC survival, treatment delivery, healthcare costs, and quality of life.
ControlsBreast cancer (BC) casesAllNon-metAll metBone metNon-bone metTotal n10212102129760452236216Any DM, n (%)2464 (24.1)4406 (43.1)3823 (39.2)223 (49.3)111 (47.0)112 (51.9)p-value2&lt;0.001&lt;0.001&lt;0.001&lt;0.001&lt;0.001Pre-existing DM1, n (%)2111 (20.1)3301 (32.2)3143 (32.2)158 (35.0)81 (34.3)77 (35.6)p-value2&lt;0.001&lt;0.001&lt;0.001&lt;0.001&lt;0.001New DM after BC1, n (%)353 (3.5)745 (7.3)680 (7.0)65 (14.4)30 (12.7)35 (16.2)p-value2&lt;0.001&lt;0.001&lt;0.001&lt;0.001&lt;0.001New DM &gt; 6 months after BC1, n (%)336 (3.3)621 (6.1)565 (5.8)56 (12.4)27 (11.4)29 (13.4)p-value2&lt;0.001&lt;0.001&lt;0.001&lt;0.001&lt;0.001HgbA1c in those with DM, Mean (SD)7.6 (1.6)7.6 (1.6)7.5 (1.6)8.3 (2.1)7.5 (1.6)8.8 (2.3)p-value21.00.001&lt;0.0010.40&lt;0.0011- For controls, values in relation to index date. 2 - p-values versus controls.
Citation Format: Tarah Ballinger, Sarah El-Azab, Ziyue Liu, Theresa Guise, Erik Imel. High prevalence and incidence of new onset diabetes in metastatic breast cancer [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 P2-08-11.