Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status.
OBJECTIVE
The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer.


METHODS
Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER- patients were analyzed. This analysis was evaluated by the validation patients' cohort of our institute prospectively.


RESULTS
Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER- group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER- patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER- patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse.


CONCLUSIONS
Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.
Park
Yeon Hee
YH
Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
Lee
Soohyeon
S
Cho
Eun Yoon
EY
Choi
Yoon La
YL
Lee
Jeong Eon
JE
Nam
Seok Jin
SJ
Yang
Jung-Hyun
JH
Ahn
Jin Seok
JS
Im
Young-Hyuck
YH
D000328:Adult; D000367:Age Factors; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D003430:Cross-Sectional Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen