Abstract P4-09-01: Impact of adjuvant chemotherapy on clinical and biological ageing in older breast cancer patients
Authors: Brouwers Barbara , Hatse Sigrid , Dal Lago Lissandra , Neven Patrick , Vuylsteke Peter , Debrock Guy , Van den Bulck Heidi , Smeets Ann , Bechter Oliver , Swerts Evalien , Kini Bailur Jithendra , Kenis Cindy , Laenen Annouschka , Dalmasso Bruna , Schöffski Patrick , Pawelec Graham , Wildiers Hans 
Published: May 2015

Abstract
Background. This prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on clinical and biological markers of ageing and frailty.
Materials and methods. Eligible patients were females ≥70y with early invasive breast cancer for whom adjuvant chemotherapy (4 x docetaxel-cyclophosphamide +/- trastuzumab and Granulocyte-Colony Stimulating Factor) was planned (ChemoG). The control group consisted of breast cancer patients for whom adjuvant chemotherapy was not indicated (ControlG). Patients were enrolled after surgery, underwent blood sampling and received full geriatric assessment (GA) and Quality of Life, (QoL) evaluation at baseline, at 3 months (3m) and 1 year (1y). GA results were summarized in a single score, LOFS (Leuven Oncology Frailty Score), ranging from 10 (very fit) to 0 (very frail). Chemotherapy administration and toxicity were recorded. An extensive (ageing) biomarker analysis is being performed, but this abstract focuses on mean leukocyte telomere length (TL), and circulating inflammatory cytokines (IL-6, IL-10, IGF-1, TNF-alfa, MCP-1, and RANTES). The primary endpoint was to assess whether adjuvant chemotherapy induces accelerated telomere attrition at 1y. Secondary endpoints were the evolution of other ageing biomarkers, LOFS and QoL during chemotherapy; correlations between ageing biomarkers, chronological age and LOFS at inclusion; and the predictive value of ageing biomarkers for functional decline, QoL decline, and chemotherapy toxicity.
Results. 57 patients were included (ChemoG), and 53 (ControlG), with mean age at diagnosis of 73,8y and 76,8y, and mean LOFS of 7,5 (SD 2,3) and 6,8 (SD 1,6). TL was similar in both groups at baseline, and decreased at 3m (p 0,05) and 1y (p 0,0009) in ChemoG, with a similar evolution in ControlG indicating no difference in evolution between both groups (test for interaction p 0,88). RANTES showed a similar decline at 1y in both groups. The other 5 markers remained stable in ControlG while significantly changing in ChemoG (significant time interaction): IL-6 decreased at 3m in the ChemoG (p 0,01) and returned to baseline values at 1y ; MCP-1 strongly decreased at 3m (p &lt;0,0001) but increased above baseline value at 1y (p &lt;0.0001) ; IGF-1 had a similar initial decline at 3m (p &lt;0,0001) yet with only slight recovery at 1y (p 0,006). On the other hand, IL-10 increased at 3m (p 0,04) but decreased at 1y (p &lt;0,0001), and TNF-alfa increased at 3m (p 0,001) and 1y (p &lt;0,0001). LOFS declined in ChemoG at 3m (p 0,0007) but returned to baseline level at 1y (p 0,6) while remaining stable over time in ControlG. Global QoL decreased slightly at 3m in ChemoG and returned to baseline while remaining stable in ControlG. IL-6 correlated most strongly with chronological age (p 0,0008) and LOFS (p 0,03) while associations were less clear for the other biomarkers. In ChemoG, MCP-1 and RANTES were associated with functional decline (IADL ≥1 point decline at 1y) but no biomarkers were associated with QoL decline and grade II-III-IV toxicity.
Conclusions. TL does not evolve differently over time in patients treated with or without chemotherapy. Chemotherapy has measurable impact on clinical frailty and other ageing biomarkers at 3 months, but these effects disappear at 1y follow-up.
Citation Format: Barbara Brouwers, Sigrid Hatse, Lissandra Dal Lago, Patrick Neven, Peter Vuylsteke, Guy Debrock, Heidi Van den Bulck, Ann Smeets, Oliver Bechter, Evalien Swerts, Jithendra Kini Bailur, Cindy Kenis, Annouschka Laenen, Bruna Dalmasso, Patrick Schöffski, Graham Pawelec, Hans Wildiers. Impact of adjuvant chemotherapy on clinical and biological ageing in older breast cancer patients [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 P4-09-01.