Abstract P3-12-08: Association of serum prealbumin (transthyretin) with anthracycline chemotherapy toxicity in patients with invasive breast cancer
Authors: Armengol-Alonso A , Zamudio-Osuna K , Cortes-Franco I , Milke-García P , León-Rodríguez E 
Published: May 2015

Background: In Mexico about 60% of invasive breast cancer (IBC) cases are diagnosed in advanced or locally-advanced stages that require systemic treatment. The chemotherapy toxicity (CTox) depends largely on the free fraction of the drug, i.e. the fraction unbound to plasmatic proteins. There is evidence that the Prealbumin (P-Alb) is a good marker of hepatic protein production. Some studies relate reduced serum proteins with CTox. The aim of the study was to correlate serum P-Alb with the degree of hematologic, gastrointestinal and skin toxicity.

Patients and Methods: Prospective cohort from January 2010 to December 2011 which recruited 41 patients with newly diagnosed IBC who received chemotherapy FAC-50 (5-fluorouracil, Adriamycin and Cyclophosphamide). Anthropometric measurements and serum determination of blood count, total protein, albumin and prealbumin were performed at baseline. The presence and degree of toxicity was evaluated on day +12 and +21 of first cycle. Toxicity was evaluated by CTCAE (Common terminology criteria for adverse events) v.4.0 We used Mann-Whitney's U test and Spearman correlation. The cutoff points for P-Alb were calculated by ROC curves.

Results: Median age was 50 years, 56% and 17% were diagnosed in cTNM stage II-III. Eighteen patients (43.9%) had grade (G) 3-4 neutropenia and 2 (4.9%) had febrile neutropenia. Nine patients (21.9%) had G. 3-4 vomiting and 3 (7.3%) patients had G. 3-4 diarrhea. We classified the patients according to neutropenia, group 1 (N= 23 patients) (56%) without or G. 1-2 toxicity; and group 2 (N=18 patients) (43.9%) with G. 3-4 toxicity. No significant differences in age, cTNM stage, performance status, total body surface area, and body mass index between the groups were identified. Lower basal P-Alb (23.1 mg/dl) was observed in group 2 compared to group 1 (28.3 mg/dl). (p = 0.001). We observed significant differences between the P-Alb medians and degree of neutropenia, vomiting and diarrhea (p = 0.003, p = 0.001 and p = 0.025). The G. of neutropenia, vomiting and diarrhea were negatively correlated with P-Alb seric concentration (r = -0594, p = &lt;0.0001, r = -0418, p = 0.006 and r = -0642, p = &lt;0.0001) respectively. A cutoff of P-Alb ≤ 25 mg/dl for G. 3-4 neutropenia had a sensitivity (S) of 77% and (E) specificity 87%. (AUC 0.84). For diarrhea of any G. a cutoff of P-Alb ≤ 26.8 mg / dl had a S 78% and E 88% (AUC 0.80). A cutoff P-Alb≤ 26 mg/dl for vomiting of any G. had a S 90% and E 76% (AUC 0.86). HR for grade 3-4 neutropenia was 23.3 (95% CI 18.8-144) (p = 0.011); diarrhea any G. HR 28.5 (95% CI 3.03-268) (p = 0.0001) and vomiting any G. HR 28.8 (95% CI 4.89-169) (p = 0.011).

Conclusion: To our knowledge this is the first prospective study describing that P-Alb is negatively correlated with the presence and grade of hematologic and gastrointestinal toxicity secondary to anthracycline breast cancer chemotherapy. A cutoff value of prealbumin &lt;26 mg/dl has a good diagnostic accuracy for predicting CTox. (neutropenia, vomiting and diarrhea). The baseline P-Alb can identify patients at increased risk of severe CTox. Our results should be validated in other cohorts with a larger number of patients.

Citation Format: A Armengol-Alonso, K Zamudio-Osuna, I Cortes-Franco, P Milke-García, E León-Rodríguez. Association of serum prealbumin (transthyretin) with anthracycline chemotherapy toxicity in patients with invasive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-08.