C-MYC AND pCR IN BREAST CANCER

 Eur J Cancer. 2011 Aug;47(12):1779-88. Epub 2011 Jul 7.

Association between c-myc amplification and pathological complete response to
neoadjuvant chemotherapy in breast cancer.

Yasojima H, Shimomura A, Naoi Y, Kishi K, Baba Y, Shimazu K, Nakayama T, Kim SJ, 
Tamaki Y, Noguchi S.

Department of Breast and Endocrine Surgery, Osaka University Graduate School of
Medicine, Osaka, Japan.

BACKGROUND: The aim of this study was to investigate whether c-myc amplification 
in human breast cancer is associated with response to neoadjuvant chemotherapy
comprising paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC).
METHODS: Tumour tissue samples were obtained before neoadjuvant chemotherapy
(P-FEC) from 100 primary breast cancer patients (stage II/III). C-myc and HER2
amplification were examined by FISH, and oestrogen receptor (ER), progesterone
receptor (PR), Ki67, and topoisomerase 2α (TOP2A) expression were examined
immunohistochemically. Pathological complete response (pCR) was defined by a
complete loss of tumour cells in the breast without any lymph node metastasis.
RESULTS: C-myc amplification was observed in 40% (40/100) of breast tumours, and 
was significantly associated with ER-negative tumours (23/40 for ER(-) versus
17/60 for ER(+), P=0.004), high histological grade tumours (11/18 for grade 3
versus 29/82 for grades 1+2, P=0.043) and TOP2A-positive tumours (28/51 for
TOP2A(+) versus 12/49 for TOP2A(-), P=0.002). pCR rate was 20% for total patients
(10.0% for ER(+) and 35.0% for ER(-)). Further, breast tumours with c-myc
amplification (c-myc(+)) showed a significantly (P=0.041) higher pCR rate (12/40)
than those without such amplification (c-myc(-)) (8/60). This association between
pCR and c-myc amplification was observed in ER-positive tumours (4/17 for
c-myc(+) versus 2/43 for c-myc(-), P=0.048) but not in ER-negative tumours (8/23 
for c-myc(+) versus 6/17 for c-myc(-), P=0.973).
CONCLUSION: Our results suggest that c-myc amplification is significantly
associated with a high pCR rate to P-FEC in breast tumours, especially in
ER-positive tumours.