Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain
Ismael Ghanem , Carlos Castañeda , Ana Perez-Campos , Oscar Toldos , Blanca Sancho Perez , Luis Manso , Jose Luis Rodriguez-Peralto , Mónica Calderón , Hernan Cortes-Funes , David Lora , Rosa Garcia-Martin , Eva Ciruelos
Background: Early triple-negative breast cancer (TNBC) patients (p) without pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT) have unsuccessful prognosis. Predictive factors for pCR are necessary in order to improve the treatment choice. The aims of the study are to determine the expression of different biomarkers (BM) in the initial biopsy (IB) of TNBC, to analyze the relationship between the BM expression and pCR, and to determine the expression changes of BM after NCT. Methods: We reviewed retrospectively the medical records of 49 TNBC p treated with NCT between 2001 and 2011 at two institutions. Expression of 14 BM in the IB and after NCT was independently analyzed by inmunohistochemistry by two pathology specialists. Staining intensity 0-1 + was considered as negative expression, and 2-3-4 + as positive. Ki 67>13% was interpreted as positive. Results: Forty-nine p with a median age of 47 years (27-79) were evaluated. Twenty-seven p (55%) had grade 3. Tumor stages were T1(2%), T2(26%), T3(39%), and T4(33%). 38p (77%) were node positive. Five p (10%) received anthracyclines and 42p (86%) anthracyclines plus taxanes. Fourteen p (29%) presented pCR, 27p (55%) partial response, 4p (8%) stable disease, 2p (4%) progressive disease, and 2p (4%) were not evaluable. The BM expression in the IB was: CD44 (88%), CK 5/6 (27%), EGFR ( 0%), Ki 67 (73%), Wt-1 (10%), p-Akt (24%), HER2 (19%), NY-ESO-1 (11%), MAGE A1 (0%), HER3 (14%), BRCA1 (84%), PTEN (12%), IGFR1 (12%) and AR (14%). Diferentially expressed BM in IB for p with and without pCR, respectively, were p-Akt 0/8(0%) vs 5/13(38%) p=0.11, CK 5/6: 4/9 (44%) vs 2/15 (13%) p=0.15 and Ki 67: 7/7(100%) vs 10/17(59%) p=0.06. The Table shows the BM expression before and after NCT for p without pCR. Conclusions: Tumor samples of TNBC show high expression of CD44, ki67, and BRCA1. Most of BM has a decrease in expression after NCT. CK 5/6, Ki 67, and p-Akt could be predictive factor for pCR, although larger prospective studies are needed.
Biomarker | n | Pre-NCT n (%) |
Post-NCT n (%) |
---|---|---|---|
CD44 | 15 | 12 (80) | 10 (67) |
CK 5/6 | 13 | 1 (8) | 1 (8) |
EGFR | 15 | 0 | 0 |
Ki 67 | 15 | 9 (60) | 6 (40) |
Wt-1 | 7 | 1 (14) | 0 |
p-Akt | 10 | 3 (30) | 0 |
HER 2 | 13 | 3 (23) | 1 (8) |
NY-ESO-1 | 12 | 0 | 1 (8) |
MAGE A1 | 13 | 0 | 0 |
HER 3 | 6 | 0 | 0 |
BRCA1 | 9 | 7 (78) | 5 (56) |
PTEN | 7 | 1 (14) | 2 (29) |
IGFR1 | 14 | 1 (7) | 0 |
Androgen R (AR) | 14 | 3 (21) | 0 |
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