Abstract P4-12-01: Long term follow up of patients (pts) with HER2positive (H+) early stage breast cancer (ESBC) treated with trastuzumab (T)
Authors: Bose R , Zanoni D , Gullo G , Fennelly D , Walshe J , Ballot J , Defrein A , O'Donovan N , Mc Dermott E , Evoy D , Silva N , Crown J 
Published: May 2016

Abstract
Background. H+BC is an aggressive variant of BC with earlier and more frequent metastatic relapse than HER2 normal disease. Following the reports in 2005 of several large random assignment trials which showed that the anti-HER2 monoclonal antibody T improved the outcome of pts with H+ESBC receiving chemotherapy, we introduced Trastuzumab (T) as a routine component of standard adjuvant (AdjRx) and neo-adjuvant (NAdjRx) therapy for all pts with H+ESBC at our institution. Others had received it investigationally from 2000-2004. We report our 14 year experience with Adj and NAdjRx with T.
Methods. We compiled a comprehensive database of all patients ever treated at our institution with Adj or neo-Adj T for H+ESBC. All pts were cross-checked through the Pathology, Pharmacy and Med Onc datasets, and all cases were individually reviewed.
Results. Out of 764 pts included in the H+BC medical oncology database, we identified 518 pts (AdjT=373, NAdjT=145) with stage I-III disease treated with T between August 2000 and October 2014. Pts characteristics: median (range) age: 54 (26-86) yrs, hormone-receptor (HR) status: HR positive (HR+) 64%/HR negative (HR-) 35%/HR unknown 1%, lymph node positive (LN+): 52% (AdjT: 44%/NAdjT 72%), systemic therapy+T: TCH [docetaxel/carboplatin/trastuzumab] 306 (59%), anthracycline and taxane regimens-85 (16%), single-agent taxane 48 (9%), other regimens or T without chemotherapy-79 (15%). The database lock out date was May 31st 2015. The median follow-up (FU) time is 50.6 (1.4-156.6) months.
The overall relapse rate (RR) in the whole population is 8.9% (AdjT 9.4%/NAdjT 7.6%) and distant RR is 8.3% (AdjT 9.1%/NAdjT 6.2%). OS rate in the whole study population is 93.4% (AdjT 92.5%/NAdjT 95.9%). RR was lower in pts with HR+ [7.2% (AdjT 7.1%/NAdjT 7.8%)] than in those with HR- [10.6% (AdjT 11.9%/NAdjT 7.4%)] disease. Among all the subgroups the lowest RR was observed in the HR+/LN- subgroup (2.7%) whilst the highest was in the HR-/LN+ subgroup (15.5%). Pts treated in the NAdjT cohort had a pathological complete response (pCR) rate of 38.6%. In the whole study population the median time to relapse (TTR) was 31.8 (7.9-97.6) months with no difference between AdjT and NAdjT cohorts. 87% of all relapses happened within 60 months of first T. Out of 6 delayed relapses (after month 60) 4 were HR+, 1was HR unknown and 1 was HR- in the form of a contralateral axillary recurrence, possibly from a second occult breast primary. Among pts treated prior to March 2010 (N=267), who have a minimum FU of 5 yrs, the RFS is 86.5% and the OS rate of 89.1%.
Conclusions. The prognosis of pts with HER2+ ESBC in the T era is excellent. Despite the large proportion of pts with LN+ disease in our database, over 90% are alive at almost 5 years. HR+ confers a better prognosis than HR- in both LN+ and LN- disease. Long-term outcome data show that nearly 90% of all relapses occur within 5 yrs from initiation of anti-HER2 therapy especially in the HR- subgroup. Late relapse is rare in HR- pts. Adjuvant hormonal therapy is likely to contribute meaningfully to the favourable outcome of HR+/HER2+ ESBC and may explain the discordance between the improved survival of ER+ Adj pts and the improved pCR reported for neoAdj T in ER+ pts.
Citation Format: Bose R, Zanoni D, Gullo G, Fennelly D, Walshe J, Ballot J, Defrein A, O'Donovan N, Mc Dermott E, Evoy D, Silva N, Crown J. Long term follow up of patients (pts) with HER2positive (H+) early stage breast cancer (ESBC) treated with trastuzumab (T). [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 P4-12-01.