Background: In women with breast cancer receiving neoadjuvant chemotherapy, residual cancer burden (RCB) predicts distant recurrence and survival. In those with high risk tumors, locoregional recurrence (LRR) remains a concern, and has been associated with type of local therapy received. We evaluated the impact of local therapy on LRR in the ISPY-2 TRIAL.

Methods: Data were analyzed in Stata 14.2, using Chi2 test, log rank test, and a Cox proportional hazards model. RCB was considered a categorical variable (0/1 versus 2/3), as described in prior publications. Breast surgery categories were lumpectomy +/- radiotherapy, or mastectomy +/- radiotherapy. Axillary surgery was defined as sentinel lymph node (SLN) surgery (≤6 nodes removed) or axillary dissection (>6 nodes).

Results: Follow up data from the I-SPY2 TRIAL were available for 630 patients (median follow up 2.76 yrs, range 0.4-7.2). Type of local therapy was significantly associated with clinical stage at presentation, with stage III patients most frequently undergoing mastectomy + radiation (p<0.001). Women with higher RCB were more likely to undergo mastectomy than those with lower RCB (61.3% vs 48.8% mastectomy rate, p=0.002), and more likely to receive adjuvant radiotherapy (62.0% vs 53.9%, p=0.048). There was no association between clinical stage, type of surgery, or radiotherapy and LRR (Table). Higher RCB was significantly associated with LRR, with 3 year locoregional recurrence free rate of 95.1% in RCB 0/1 versus 89.9% in RCB 2/3 (p=0.003).

In a Cox model adjusting for clinical stage, tumor subtype, surgical therapy, RCB status, nodal radiation, and age, significant predictors for LRR were tumor subtype and RCB status. Hazard ratio (HR) for LRR in those with RCB 0/1 was 0.39 compared to those with RCB 2/3 (95% CI 0.17-0.87, p=0.021). There was no difference in LRR between breast conservation and mastectomy; within the breast conservation group, those who had lumpectomy alone had higher hazard of LRR compared to those having lumpectomy + radiation (HR 3.1, 95% CI 1.1-9.2, p=0.043).

Conclusions: Extent of surgical therapy was not associated with local tumor control, regardless of advanced tumor stage at presentation. Rather, tumor biology and response to therapy were the best predictors of LRR. These data highlight the opportunity to minimize the morbidity of extensive surgical therapy for patients with excellent response to systemic therapy.

LRR rates by clinical features and treatment status

  FrequencyLRR RateP value
Clinical Stage    0.5 
240 (47.5%) 5.8%   
II 185 (36.6%) 8.7%   
III 80 (15.8%) 6.3%   
Tumor Subtype    0.014 
ER+PR+Her2- 161 (26.4%) 3.1%   
ER+PR-Her2- 56 (9.2%) 3.6%   
Her2+ 176 (28.9%) 6.3%   
Triple negative 216 (35.5%) 11.1%   
Local therapy    0.169 
Lumpectomy 85 (13.5%) 11.8%   
Lumpectomy with radiation 198 (31.4%) 5.6%   
Mastectomy 173 (27.5%) 5.2%   
Mastectomy with radiation 174 (27.6%) 8.6%   
Axillary surgery    0.23 
None 5 (0.8%) 20%   
SLN 329 (52.2%) 5.8%   
ALND 296 (47%) 8.5%   
Axillary radiation    0.535 
Yes 42 (6.7%) 9.5%   
No 588 (93.3%) 7.0%   
Axillary management    0.2 
No surgery or radiation 5 (0.8%) 20.0%   
SLN 312 (50%) 5.3%   
SLN+Axillary radiation 17 (2.7%) 8.3%   
ALND 271 (43%) 10.3%   
ALND+Axillary radiation 25 (4%) 5.4%   
RCB    0.002 
0/1 293 (50.1%) 3.8%   
2/3 292 (49.9%) 10.3%   
  FrequencyLRR RateP value
Clinical Stage    0.5 
240 (47.5%) 5.8%   
II 185 (36.6%) 8.7%   
III 80 (15.8%) 6.3%   
Tumor Subtype    0.014 
ER+PR+Her2- 161 (26.4%) 3.1%   
ER+PR-Her2- 56 (9.2%) 3.6%   
Her2+ 176 (28.9%) 6.3%   
Triple negative 216 (35.5%) 11.1%   
Local therapy    0.169 
Lumpectomy 85 (13.5%) 11.8%   
Lumpectomy with radiation 198 (31.4%) 5.6%   
Mastectomy 173 (27.5%) 5.2%   
Mastectomy with radiation 174 (27.6%) 8.6%   
Axillary surgery    0.23 
None 5 (0.8%) 20%   
SLN 329 (52.2%) 5.8%   
ALND 296 (47%) 8.5%   
Axillary radiation    0.535 
Yes 42 (6.7%) 9.5%   
No 588 (93.3%) 7.0%   
Axillary management    0.2 
No surgery or radiation 5 (0.8%) 20.0%   
SLN 312 (50%) 5.3%   
SLN+Axillary radiation 17 (2.7%) 8.3%   
ALND 271 (43%) 10.3%   
ALND+Axillary radiation 25 (4%) 5.4%   
RCB    0.002 
0/1 293 (50.1%) 3.8%   
2/3 292 (49.9%) 10.3%   

Citation Format: Silverstein J, Suleiman L, Yau C, Price ER, Singhrao R, Yee D, DeMichele A, Isaacs C, Albain KS, Chien AJ, Forero-Torres A, Wallace AM, Pusztai L, Ellis ED, Elias AD, Lang JE, Lu J, Han HS, Clark AS, Korde L, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Wood WC, Park JW, Liu MC, Olopade O, Leyland-Jones B, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, I-SPY 2 TRIAL Consortium, Berry DA, Asare SM, Esserman LJ, Boughey JC, Mukhtar RA. The impact of local therapy on locoregional recurrence in women with high risk breast cancer in the neoadjuvant I-SPY2 TRIAL [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-01.