Abstract P4-05-14: The PI3KCA mutations are frequent and remain along with recurrence of liver metastases from breast cancer in women who underwent up to 3 liver resections
Authors: Ruiz Archie , Sebagh Mylène , Saffroy Raphaël , Allard Marc-Antoine , Bouvet De La Maisonneuve Philippe , Bosselut Nelly , Adam René , Lemoine Antoinette , Morere Jean-François 
Published: May 2015

The Liver resection associated with anticancer and hormonal treatments for metastatic breast cancer results in improved patient survival. However, many patients have tumor recurrence. The frequently observed mutations in PIK3CA that have been associated with resistance to chemotherapy and to anti-HER2 or anti-estrogen therapies treatment, could be involved in the recurrence of liver metastases (and targeted in the future). Therefore, we have analyzed the incidence of the two major 'hot spot' mutations in the helical and catalytic domains of PI3KCA in the liver metastases from breast cancer (LMBC) isolated in a selected cohort of 20 women who underwent at least 2 liver resections with curative intent. Twelve of them had a third hepatectomy. The first hepatectomy was between 1 to 6 yrs after the diagnosis of primary tumors. A total of 73 LMBC were analyzed.

The characteristics of the LMBC at the first hepatectomy : the median age was 52 yrs (range: 30 to 64). Five patients had a solitary tumor whereas the others had up to 5 nodules. The tumor stages varied from stage IA to IIIA and were ductal tumors for 80% of them. Hormonal status varied from the negativity for the receptors to estrogen (ER), progesterone (PR) and HER2 (n=4), to the clearcut positivity ER (n=2), PR (n=3), HER2 (n=4). Out of 20 patients, 6 had LMBC carrying PI3KCA mutations (1 H1047R, 6 E545K). When LMBC were multinodular, all the nodules except one harbored the PI3KCA mutation.

The characteristics of the recurrent LMBC: out of the 6 LMBC with PI3KCA mutations, 4 recurred and underwent a third hepatectomy. One patient whose LMBC did not harbor any PI3KCA mutations at the first liver resection had mutant PI3KCA in the LMBC from the second to the fourth liver resection. All the nodules of the 5 women harbored the same PI3KCA mutation. In parallel, 7 women underwent a third liver resection with no PI3KCA mutations in any of the nodules analyzed. There was no relationship between the recurrence of LMBC with PI3KCA mutations and the surgical margins. The frequency of women whose LMBC carry PI3KCA mutations increased at the third hepatectomy

In conclusion, PI3KCA mutations are frequently observed in LMBC in all the nodules and persist along with the recurrence. However, PI3KCA could constitute a new target in the neoadjuvant setting before hepatectomy.

Citation Format: Archie Ruiz, Mylène Sebagh, Raphaël Saffroy, Marc-Antoine Allard, Philippe Bouvet De La Maisonneuve, Nelly Bosselut, René Adam, Antoinette Lemoine, Jean-François Morere. The PI3KCA mutations are frequent and remain along with recurrence of liver metastases from breast cancer in women who underwent up to 3 liver resections [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 P4-05-14.