Abstract P3-13-05: Long-term outcome of neoadjuvant endocrine therapy followed by breast conserving surgery
Authors: Yau JD , Turnbull AK , Renshaw L , Keys J , Leeper A , Thomas JS , Dixon JM 
Published: February 2018

Background:Neoadjuvant therapy (NET) in women with large or locally advanced estrogen receptor(ER)-rich breast cancers (BC) allows the option of breast-conserving surgery (BCS) + radiotherapy (RT). The aim was to study the long term safety of this strategy.

Methods: 280 postmenopausal women (median age 77, range 50-95, table 1) with ER-rich BC had BCS after NET (median duration 4.8 mths, range 1.7-42.8 mths). 221 (79%) received only letrozole. 59 (21%) began on letrozole and were switched to anastrozole, exemestane or tamoxifen due to adverse events or lack of clinical response. 200 patients (71%) had adjuvant RT (RTgroup) and 25 (9%), adjuvant chemotherapy. Median follow-up = 5.5 years.

Table 1: Clinical characteristics of patients.CharacteristicNo. PatientsTumour SizeT131 (11%)T2169 (60%)T314 (5%)T456 (20%)Unknown10 (4%)Grade136 (13%)2153 (55%)370 (25%)Unknown21 (7%)Nodes+ve101 (36%)-ve177 (63%)Unknown3 (1%)ER Allred615 (5%)762 (22%)8203 (73%)

Results:

254 patients had NET response data. 74% had a clinical response. NET response was higher for grade 1 (84%) than for 2 (73%) or 3 (72%) cancers.

Actuarial local recurrence rates (LRR) were 8% (95%CI±0.04) and 12% (95%CI±0.06) at 5 & 10 years. Actuarial overall BC recurrence rates were 14% (95%CI±0.04) and 27% (95%CI±0.12) at 5 & 10 years, with BCS death rates of 7% (95%CI±0.04) and 14% (95%CI±0.10) at 5 & 10 years, showing only half with recurrence died from BC. Crude all-cause mortality but not BC-specific survival (BCSS) favoured those who had adjuvant RT (P&lt;0.001) or chemotherapy (P=0.006). The 15-year rate was 50.9%, while BCS death rate was only 7.3%.

Positive nodes were associated with worse overall recurrence free survival (RFS) (P=0.007) but not local RFS or BCSS. Tumour size was not associated with RFS or BCSS. Tumour grade was not associated with RFS but grade 3 patients had a lower BCSS (P=0.002) compared to patients grade 1/2 cancers.

RT was associated with improved LRR (P&lt;0.0001) and overall RR (P=0.038): 5 & 10 year in RTgroup were 5% (95%CI±0.04) + 7% (95%CI±0.04) vs 9% (95%CI±0.12) + 31% (95%CI±0.24) in no-RTgroup. The 5 & 10 year ORR in the RTgroup was 14% (95%CI±0.06) and 39% (95%CI±0.16) vs 28% (95%CI±0.16) + 38% (95%CI±0.24) in the no-RTgroup. Although differences were not significant, BCSS was higher in the no-RTgroup: 5 & 10 yearly BCSS rates were 10% (95%CI±0.04) and 20% (95%CI±0.12) vs 6% (95%CI±0.08) + 12% (95%CI±0.14) in RTgroup.

16/67 patients with T3/4 cancers with no RT had lower overall RFS (P=0.018) but no difference in local RFS. 13/98 patients with node +ve disease with no RT had lower LRR (P=0.002) and overall RR (P=0.024). 54/169 node -ve patients with no RT had lower LRR (P=0.019) but similar overall RR. 50/183 patients with grade 1/2 cancers had no RT and had lower LRR (P&lt;0.0001) and overall RR (P=0.049). BCSS was not associated with RT use in subgroups related to tumour size, node status or grade.

Discussion:

· Response to NET is not worse in ER rich grade 3 or node positive cancers.

· After NET, BCS and RT provides excellent LRR.

· BCSS rates were low; most died of other causes.

· NET followed by BCS and RT is safe even for grade 3 and node positive cancers.

· BCS alone provides adequate disease control for majority with significant co-morbidities.

Citation Format: Yau JD, Turnbull AK, Renshaw L, Keys J, Leeper A, Thomas JS, Dixon JM. Long-term outcome of neoadjuvant endocrine therapy followed by breast conserving surgery [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 P3-13-05.