PREDICTIVE FACTORS FOR pCR IN HER2+ BREAST CANCER

Clin Cancer Res. 2016 Jan 12. pii: clincanres.0965.2015. [Epub ahead of print]

PTEN EXPRESSION AND p4EBP1 IMMUNOREACTIVE SCORE AS PREDICTOR FOR pCR IN HER2 POSITIVE BREAST CANCER.

Loibl S1, Darb-Esfahani S2, Huober J3, Klimowicz A4, Furlanetto J5, Lederer B6, Hartmann A7, Eidtmann H8, Pfitzner BM9, Fasching PA10, Tiemann K11, Jackisch C12, Mehta K13, von Minckwitz G14, Untch M15, Denkert C16.

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Abstract

BACKGROUND: 

Phosphatidylinositol 3-kinase (PI3K)/AKT pathway and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) aberrations are common in breast cancer. We investigated the correlation between PIK3CA, PTEN, p4EBP1 (phosphorylated E4 binding protein 1) and pathological complete response (pCR) in patients receiving neoadjuvant therapy.

METHODS: 

We retrospectively evaluated PIK3CA, PTEN and p4EBP1 protein expression in centrally HER2-positive patients (n=181) who received EC/trastuzumab followed by docetaxel/trastuzumab alone or concomitant/followed by capecitabine within the GeparQuattro study. PTEN was assessed using the automated quantitative immunofluorescence analysis and was analysed as a dichotomic variable. p4EBP1 was assessed by immunohistochemistry and used as a continuous and dichotomic variable.

RESULTS: 

p4EBP1 was available from 137, PTEN from 108, PIK3CA genotype from 83 patients. Overall, pCR rate in PTEN low tumors was 27.6%, in PTEN high 57.1% (p=0.010). pCR rates were not statistically different between PIK3CA wildtype (wt) and mutant (mut) (35% vs 22%) or p4EBP1 IRS≤4 and IRS>4 (39% vs 33%). pCR rate was 57.1% (8/14) in PTEN high/PIK3CA wt and decreased to 15.4% in PTEN low/PIK3CA mut tumors (p=0.023). In multivariable analysis adjusted for baseline parameters, PTEN independently predicted pCR in the following cohorts: overall (OR 7.54 [95%CI 2.03-28.06] p=0.003), PIK3CA wt (OR 23.81 [1.75-324.05] p=0.017), p4EBP1 IRS>4 (OR 11.53 [1.84-72.24] p=0.009), and HR-positive (OR 40.91 [2.93-570.44] p=0.006). p4EBP1 was independently predictive for pCR in PIK3CA wt tumors (OR 0.14 [0.03-0.78] p=0.025).

CONCLUSION: 

The study showed the potential role of PIK3CA genotype, PTEN and p4EBP in predicting pCR after anthracycline-taxane based chemotherapy and anti-HER2 treatment.