History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium

Albina N. Minlikeeva, Jo L. Freudenheim, Rikki A. Cannioto, J. Brian Szender, Kevin H. Eng, Francesmary Modugno, Roberta B. Ness, Michael J. LaMonte, Grace Friel, Brahm H. Segal, Kunle Odunsi, Paul Mayor, Emese Zsiros, Barbara Schmalfeldt, Rüdiger Klapdor, Thilo Dӧrk, Peter Hillemanns, Linda E. Kelemen, Martin Kӧbel, Helen Steed, Anna de Fazio, on behalf of the Australian Ovarian Cancer Study Group, Susan J. Jordan, Christina M. Nagle, Harvey A. Risch, Mary Anne Rossing, Jennifer A. Doherty, Marc T. Goodman, Robert Edwards, Keitaro Matsuo, Mika Mizuno, Beth Y. Karlan, Susanne K. Kjær, Estrid Høgdall, Allan Jensen, Joellen M. Schildkraut, Kathryn L. Terry, Daniel W. Cramer, Elisa V. Bandera, Lisa E. Paddock, Lambertus A. Kiemeney, Leon F. Massuger, Jolanta Kupryjanczyk, Andrew Berchuck, Jenny Chang-Claude, Brenda Diergaarde, Penelope M. Webb, Kirsten B. Moysich, on behalf of the Ovarian Cancer Association Consortium

Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes. History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94. Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.