Abstract P5-21-06: Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC)
Authors: Ferro Antonella , Caldara Alessia , Dipasquale Mariachiara , Trentin Chiara , Triolo Renza , Barbareschi Mattia , Bernardi Daniela , Pellegrini Marco , Cazzolli Daniela , Berlanda Gabriella , Gasperetti Fabio , Maines Francesca , Tuttobene Paolina , Caffo Orazio , Galligioni Enzo 
Published: May 2015

Abstract
BACKGROUND:
IBC is a heterogeneous disease with several subtypes molecularly identified by gene expression profile. Since subtypes defined by immuhistochemistry (IHC) panel are similar although not identical to molecular subtypes, IHC may represent an easier alternative to identify them.
PURPUSE:
To assess the clinical outcomes of pts who received NC for IBC and the differences by IHC-related subtypes.
METHODS:
We retrospectively reviewed the clinical records of the pts treated with NC for stage II-III IBC from 2000 to 2013. For each pt we recorded baseline tumor size, type of NC [which consisted of anthracyclines (A) + taxanes (T) in HER2- and T + trastuzumab (H) ± A in HER2+ pts), type of surgery, pathological response (pCR defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS). IHC subtypes were defined according to ER and PgR expression, Ki-67 level, and HER2 status:
Luminal A (LA): ER and PR+, neg HER2 and Ki67&lt; 14% (= 3%)
Luminal B (LB): ER and/or PR+, neg HER2 and Ki67≥14% (=30%)
Luminal HER2 (LHER2): ER and/or PR+, positive HER2 and any Ki67 (=27%)
HER2 positive (HER2+): neg ER and PR, positive HER2 and any Ki67 (=12%)
Triple negative (TN): neg ER and PR, neg HER2 and any Ki67 (13%)
Unknown subtype in 33 cases (15%)
The loco-regional and distant RFS and OS were evaluated according to pCR.
pCR and survival outcomes were also assessed on the basis of both pre- and post- NC Ki67 levels.
RESULTS:
In the consecutive series of 213 pts who received NC median age was 50 yrs (r. 25-75). The NC consisted of an A+T based regimen in HER2 negative (145 pts) and of a T+ H with A (31 pts) or without A (34 pts) in HER2+ disease.
Only 14 did not receive surgery: 10 for distant metastases development and 4 because still on NC. Quadrantectomy was performed in 120 pts (60%). Among all pts, pCR was achieved in 44 pts(22%) with further 4 pts showing a RT ≤1 mm.
Relationship between pCR and subtypes, ki67 and recurrence rate LA (%)LB (%)LHER2 (%)HER2+TN (%)Median Ki67 (%)Recurrence Rate (%)pCR012.542.527.517.5484.5No pCR10042.329.28.814.63731.5p Value &lt;0.001 =0.001
All but 19 HER2+ pts (84) received H obtaining pCR in 38% of cases regardless chemotherapy type (A-based 35% vs Not A- 38%)
The median follow-up was 45 months (range 1-166 ms).
The 4y-RFS and OS were better in which achieved pCR than those did no (RFS 92 vs to 74%; p=0.0014 and OS 95 vs 78%; p=0.0074).
Median Ki67 in pretreated core biopsy was 40 compared to 27% in post-NC RT. Patients with high (&gt;30%) post-NC Ki67 levels showed significantly higher risk for disease relapse (4 y-RFS 60%; p=0.0019) and death (4y OS 71%; p=0.018) compared with patients with &lt;15% (4y-RFS 93 and OS 88%) or &gt;15-30 Ki67 levels (4y-RFS 83 and OS 82%).
CONCLUSIONS:
According to literature data, pts achieving pCR after NC showed better RFS and OS compared to no pCR pts. The pCR rate was significantly higher in aggressive subtypes (HER2 and TN). In HER2 disease, pCR was achieved by using chemo + H, irrespective of A-addition. Interestingly high pre-NC KI67 levels seem to predict the possibility obtaing pCR, while post-NC Ki67 levels seem to be of prognostic value in pts who do not receive pCR.
Citation Format: Antonella Ferro, Alessia Caldara, Mariachiara Dipasquale, Chiara Trentin, Renza Triolo, Mattia Barbareschi, Daniela Bernardi, Marco Pellegrini, Daniela Cazzolli, Gabriella Berlanda, Fabio Gasperetti, Francesca Maines, Paolina Tuttobene, Orazio Caffo, Enzo Galligioni. Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC) [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 P5-21-06.