ER, PgR, Ki67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab.
BACKGROUND
Neoadjuvant chemotherapy (NAC) with taxanes followed by fluorouracil, epirubicin, and cyclophosphamide (FEC), and concurrent trastuzumab is a potent regimen for HER2 over-expressing breast cancer. A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear. In the present study, we determined whether pCR was related to histological grade (HG) and several biological factors including p27(Kip1). We also assessed the prognosis of the pCR and non-pCR groups, and expected differences between those positive and negative for lymph node metastasis after chemotherapy.


METHODS
A total of 129 Japanese women with HER2-positive invasive breast cancer received either paclitaxel or docetaxel followed by FEC, with the concomitant administration of trastuzumab. The statuses of HG, ER, PgR, Ki67, and p27(Kip1) were evaluated to determine their relationship with pCR. Relapse-free survival (RFS) and overall survival (OS) were also analyzed for their relationship with pCR and pathological nodal involvement.


RESULTS
pCR was obtained in 84 out of 129 patients and the pCR rate was 65.1%. The pCR rates related to 5 factors were as follows: HG (grade 3, 70.0% vs. grades 1-2, 36.8%), ER (negative, 78.6% vs. positive, 40.0%), PgR (negative, 75.3% vs. positive, 38.9%), Ki67 (high, 72.0% vs. low, 47.2%), and p27(Kip1) (low, 71.0% vs. high, 50.0%). RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018). Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002).


CONCLUSIONS
High-HG, low-ER, low-PgR, high-Ki67, and low-p27(Kip1) were identified as predictive factors of pCR in NAC with trastuzumab, while pCR and negative nodes were predictive of better survivals.
Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan. chachagot-a-mail@hotmail.co.jp.
Sasagu
S
Kurozumi
Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan. ino@cancer-c.pref.saitama.jp.
Kenichi
K
Inoue
Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan. takei-hiroyuki@nms.ac.jp.
Hiroyuki
H
Takei
Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan. hiromatsu@cancer-c.pref.saitama.jp.
Hiroshi
H
Matsumoto
Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan. mkurosumi@cancer-c.pref.saitama.jp.
Masafumi
M
Kurosumi
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. junhorig@gunma-u.ac.jp.
Jun
J
Horiguchi
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. takeyoshi@gunma-u.ac.jp.
Izumi
I
Takeyoshi
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. tetsunari.oyama@gmail.com.
Tetsunari
T
Oyama
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human