Prediction of a Pathological Complete Response Defined as ypT0/is ypNx in the Setting of a Preoperative Systemic Therapy (EC-T+-Trastuzumab) of Invasive Breast Carcinoma by Evaluating bcl2 and TP53 on the Pretherapeutic Core Needle Biopsy Specimen
Daniel Klein, Katja C Siegmann-Luz, Markus Hahn, Tanja N Fehm, Ulrich F Vogel. University Hospital, Eberhard-Karls-University, Tuebingen, Baden-Wuerttemberg, Germany
Background: Preoperative systemic therapy may be the best tool to acquire information on the response of a malignant tumor to chemotherapy. To avoid unnecessary toxicity it would be helpful to predict the pathological complete response (pCR) for a certain chemotherapy regimen on the pretherapeutic core needle biopsy specimen (pCNBS).
Design: 126 patients with invasive breast cancer were treated preoperatively (GeparQuattro study: Epirubicin, Cyclophosphamide, Docetaxel, +-Trastuzumab). Besides ER, PGR and HER2 TP53 and bcl2 were determined immunohistochemically on the pCNBSs. Additional molecular analysis of TP53 was done in a few selected cases.
Results: Using the TP53 and bcl-2 expression three groups of breast carcinomas could be designed to predict the pCR defined as ypT0/is ypNx:
1. bcl2(% positive tumor cells) > TP53 (%): Prediction: No pCR.
n = 71; no pCR: 69/71 (97%). Especially invasive lobular carcinomas belong to this group.
Subgroup: HER2+: non-pCR: 7/8 (87%). The pCR case: unusual strong bcl2.
2. bcl2 < TP53 with TP53 not 0 or not 90-100%: Prediction: pCR.
n = 17; pCR: 15/17 (88%); pCR: 15/16 (94%) if an adenosquamous carcinoma is excluded.
Subgroup: HER2+: pCR: 10/10 (100%).
3. bcl2 <= TP53 with TP53 = 0 or TP53 = 90-100%: Prediction: Not possible without an additional molecular analysis of TP53.
n = 38; pCR: 14/38 (36%). Preliminary sequence analysis of a few cases of this group revealed TP53 mutations in the exons 5-8 in non-pCR cases, whereas a wild type TP53 could be found in the pCR cases.
Subgroup: HER2+ TP53>=90%: n = 6; pCR: 5/6 (83%). The non-pCR case: no trastuzumab; point mutation exon 5.
Subgroup: HER2+ TP53 = 0: n = 4; non-pCR: 3/4 (75%). One of these cases sequenced: point mutation exon 7.
Conclusions: The immunohistological determination of TP53 and bcl2 on the pCNBSs allows the definition of three groups of breast carcinomas to predict the therapy response. According to literature the evaluation of the expression signature for the TP53 status seems to be superior to the sole sequence analysis of TP53. The prediction of ypN0 cannot be achieved by this classification.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 27, Wednesday Morning