Abstract P1-07-07: Overtime distribution and predictors of local recurrences (LRs) in patients with hormone receptor positive (HR+) and node positive (N+) breast cancers (BCs): 10 -year follow-up analysis of UNICANCER-PACS 01 and PACS04 trials
Authors: Pistilli B , Filleron T , Mazouni C , Zingarello A , Lacroix-Triki M , Rivera S , Coudert B , Serin D , Canon J-L , Campone M , Bachelot T , Goncalves A , Levy C , Cottu P , Petit T , Eymard J-C , Tunon De Lara C , Roché H , Roca L , Lemonnier J , Delaloge S 
Published: February 2018

Abstract
Purpose:Incidence of LRs in patients (pts) treated for HR+ HER2- localized BC and distribution overtime have not been described in recent years after introduction of new generation of adjuvant therapies and more extensive use of radiotherapy. We evaluated the incidence and distribution overtime of LRs in pts with HR+ HER2- N+ BCs who entered PACS 01 and PACS04 trials.
Patients and Methods: Data were analyzed from 2909 pts with HR+/HER2- BC out of 5008 included in both trials. Pts underwent mastectomy or lumpectomy plus axillary dissection for a localized N+ BC and, according to study design, were randomized to: 6 cycles of FE100C (standard arm) versus FE100C x 3 cycles followed by docetaxel 100 mg/m2 x 3 cycles (FEC-D) (PACS01) or 6 cycles of Epirubicin 75mg/m2 and Docetaxel 75 mg/m2 (ED75)(PACS04). Loco-regional radiotherapy was mandatory after lumpectomy and recommended in other cases. All pts received 5 years of hormone therapy (HT). A competing risk multivariate analysis was conduct using Fine and Gray model to identify risk factors associated to isolated LRs. Competing events were nodal recurrence, contralateral BC, distant metastasis and death. Cumulative incidence associated to each event was estimated by a Kablfleish-Prentice estimator.
Results: Pts' median age was 50 (22-65); 67.2% underwent lumpectomy, 32.8% mastectomy; 67.6% had 1 to 3 N+, 32.4% more than 3 N+; 45.7% had lymphovascular invasion; 49.5% received FE100C, 35.8% ET75, 14.7% had FEC-D; while radiotherapy was given to 97.3% and HT to 92.2%, of whom 90.5% received tamoxifen. At a median follow-up of 9.1 years, 60 pts (2.1%) experienced LR as first event. The 5-year and 10-year cumulative incidence of LRs were 1.04% and 2.53%, respectively. The cumulative incidence of LRs increased from the 5th year, and the annual risk tended to remain constant over time. Multivariate analysis of competing risk showed that younger age, conservative surgery and omission of HT (not prescribed or non-adherence) were independently associated with risk of developing LRs.
Table 1. Multivariate analysis on competing risk of predictors of LRsVariablesHR 95%CIP valueAge at entry (&lt;35 years, ≥ 35)*0.95 [0.92; 0.99]0.009Mastectomy, lumpectomy0.39 [0.17; 0.86]0.020&gt; 20mm, ≤20 mm0.68 [0.37; 1.24]0.203N+ &gt;3, 1-31.73 [0.99; 3.02]0.055Grade II/III, I1.06 [0.50; 2.24]0.885PR+,PR-1.78 [0.70; 4.53]0.223Type of chemotherapy 3FEC-3D, 6FEC/6ET1.32 [0.65; 2.69]0.446Number of cycles 6, &lt;60.71 [0.17; 0.75]0.630Hormone therapy Yes,No0.36 [0.17; 0.75]0.006*treated as continuous variable
Conclusion: Our analysis showed that incidence of LRs in pts with HR+ N+ BCs treated within PACS trials were considerably lower as compared to earlier studies. These findings may reflect differences in treatment era, as the more extensive use of radiotherapy and new generation of adjuvant chemotherapy. Despite current adjuvant strategies, young age at diagnosis and omission of HT remain independent risk factors of LRs.
Citation Format: Pistilli B, Filleron T, Mazouni C, Zingarello A, Lacroix-Triki M, Rivera S, Coudert B, Serin D, Canon J-L, Campone M, Bachelot T, Goncalves A, Levy C, Cottu P, Petit T, Eymard J-C, Tunon De Lara C, Roché H, Roca L, Lemonnier J, Delaloge S. Overtime distribution and predictors of local recurrences (LRs) in patients with hormone receptor positive (HR+) and node positive (N+) breast cancers (BCs): 10 -year follow-up analysis of UNICANCER-PACS 01 and PACS04 trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-07.