Abstract P5-08-49: Incidence and prognostic importance of hyponatremia in a cohort of patients with breast cancer
Authors: Castillo JJ , Glezerman IG , Boklage SH , Lamerato LE , Chiodo JA , Tidwell BA , Schulman KL 
Published: May 2016

Abstract
Background: It has been suggested that hyponatremia (HN) may be a negative prognostic factor in patients with cancer but little research has been conducted specifically in breast cancer (BC). We measured the incidence of hyponatremia (hypervolemic and euvolemic) after BC diagnosis and its prognostic importance for progression free (PFS) and overall survival (OS).
Methods: This retrospective cohort analysis utilized data from the Henry Ford Health System electronic medical record, tumor registry, and administrative databases. Study data were collected electronically and via medical record abstraction. Adults diagnosed (2002-2010) with incident invasive BC were selected if they had a known disease stage at the time of tumor registration, were classified as an analytic case, had ≥ 1 administration of chemo/radiation therapy ≤ 6 months from diagnosis, met continuous enrollment thresholds, and did not experience hypovolemic HN post index. Only the first tumor registered from each patient was considered study-eligible. Hypervolemic or euvolemic HN incidence (serum sodium ≤ 135 mEq/L) was measured per 1000 person-years (PY) of observation and classified as mild (131–135 mEq/L), moderate (125–130 mEq/L) or severe (&lt;125 mEq/L) based on the lowest observed value. A Cox proportional hazards model was used to assess the prognostic value of HN as a time-varying covariate on PFS and OS while controlling for age, race, income, morphology code, diagnosis year, cancer stage at diagnosis, performance status at diagnosis, and hormone receptor status.
Results: 527 patients were eligible (mean [SD] age 56.4±11.3 years, 61% Caucasian). Mean (SD) follow-up was 3.7±2.8 years. Eighty-five percent of patients had infiltrating ductal carcinoma; 72% and 65% had estrogen or progesterone sensitive tumor, respectively; 35% were HER2 positive; and 15% had triple negative disease. Eighty-two percent of patients had early stage (I, II) disease at time of diagnosis. HN episodes (n=377) occurred in 204 patients (39%) at a rate of 193 per 1000 PY (95% CI, 174–213.5), with 89% of the total episodes (337/377) classified as mild, 10% (36/377) as moderate, and 1% (4/377) as severe. Additionally, 7% of all BC patients (37/527) had at least one episode of moderate/severe HN. Median time to first HN episode was 174.5 days and the median HN episode duration was 24.0 days. Five year OS in patients developing HN was 92%, compared to 97% in patients who never developed HN. Hazard ratio (95% CI, p-value) for OS in the HN group was 4.4 (1.5-12.7; p=0.006) after controlling for age, diagnosis year, race, income, morphology, cancer stage, performance status, and hormone receptor status. Fifty patients had progressive disease during follow-up with a mean (SD) time to progression of 763.4 (758.1) days. Hazard ratio (95% CI, p-value) for PFS in the HN group was 1.4 (0.8-2.7; p=0.262) after controlling for age, race, income, morphology, cancer stage, performance status, and hormone receptor status.
Conclusions: Incidence of hypervolemic or euvolemic HN is high (39%) after a BC diagnosis, and the occurrence is associated with significantly poorer OS. A significant impact on disease progression was not observed.
Citation Format: Castillo JJ, Glezerman IG, Boklage SH, Lamerato LE, Chiodo JA, Tidwell BA, Schulman KL. Incidence and prognostic importance of hyponatremia in a cohort of patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-49.