Proliferation Determined by Ki-67 Defines Different Pathologic Response to Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer.
BACKGROUND
This study aimed to assess the role of proliferation measured by Ki-67 as a predictive factor for pathologic complete response (pCR) to trastuzumab-based chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2(+)) breast cancer (BC).


METHODS
A total of 81 patients with HER2(+) BC were treated with a sequential schedule consisting of 4 cycles of cyclophosphamide (600 mg/m(2)) and doxorubicin (60 mg/m(2)) every 3 weeks, followed by 4 cycles of weekly paclitaxel (80 mg/m(2)) or docetaxel (100 mg/m(2)) every 3 weeks combined with trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg every 3 weeks) as neoadjuvant treatment. Histologic subgroups classified by hormone receptor (HR) expression and Ki-67 index were 17% HR(+)/Ki-67 ≥ 50%, 41% HR(+)/Ki-67 < 50%, 25% HR-negative (HR(-)) Ki-67 ≥ 50%, and 17% HR(-)/Ki-67 < 50%.


RESULTS
pCR, defined as the absence of invasive cells in the breast and axillary lymph node, was achieved in 33 patients (41%). The median Ki-67 expression was significantly higher in tumors with pCR (53%) compared with tumors without pCR (30%) (P < .001). Receiver operating characteristic (ROC) curve methodology suggested that 50% was the optimal Ki-67 cutoff point to best identify patients who achieved a pCR. The pCR rate was significantly different between histologic subgroups: HR(-)/Ki-67 ≥ 50% (70%), HR(+)/Ki-67 ≥ 50% (71%), HR(-)/Ki-67 < 50% (22%), and HR(+)/Ki-67 < 50% (18%) (P < .001). A multivariate analysis revealed that a Ki-67 marker ≥ 50% was the only independent predictive factor of pCR (P = .003; odds ratio [OR], 0.133; 95% confidence interval [CI], 0.036-0.5). The median follow-up was 32 months (range, 14-48 months). Patients who achieved a pCR had significantly lower recurrence (P = .001) and higher overall survival (OS) (P = .013) compared with those who did not. There were no statistically significant differences in disease-free survival (DFS) and OS in relation to HRs, the Ki-67 marker as a continuous or categorical variable, and histologic subgroups.


CONCLUSIONS
Proliferation determined by Ki-67 expression ≥ 50% was an independent predictive factor for pCR in patients with HER2(+) BC treated with trastuzumab-based chemotherapy.
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain. Electronic address: asmoncomed@yahoo.es.
Alfonso
A
Sánchez-Muñoz
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain.
Victor
V
Navarro-Perez
Medical Oncology Service, Complejo Hospitalario de Jaén, Jaén, Spain.
Yessica
Y
Plata-Fernández
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain.
Angela
A
Santonja
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain.
Ignacio
I
Moreno
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain.
Nuria
N
Ribelles
Medical Oncology Service, Hospital Universitario Virgen de la Victoria of Málaga, Málaga, Spain.
Emilio
E
Alba
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D059186:Chemoradiotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab / Q000008:administration & dosage
D003520:Cyclophosphamide; D003841:Deoxycytidine; D004317:Doxorubicin; D019394:Ki-67 Antigen; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
HER2-positive breast cancer; Ki-67 marker; Neoadjuvant trastuzumab-based chemotherapy; Pathologic complete response; Predictive factor