From DEPARTMENT OF ONCOLOGY AND PATHOLOGY Karolinska Institutet, Stockholm, Sweden PROGNOSTIC AND PREDICTIVE FACTORS IN VIETNAMESE BREAST CANCER: A COMPARISON WITH SWEDISH PATIENTS AND EFFECT ON SURVIVAL VU

Breast cancer is a leading cause of cancer death among women in Western and Asian countries. Previous studies showed that Asian and African-American patients more often had poor tumor prognostic factors than Caucasian patients. There are however only few reports on tumor prognostic factors and survival in Vietnamese breast cancer patients. The aim of this study was to investigate prognostic/predictive factors in Vietnamese operable breast cancer which were compared with those in Swedish breast cancer patients and to estimate survival. Primary breast cancer tissues were collected randomly for analysis of hormone receptors, HER2 status and cell proliferation. Clinical information, pathology report and treatment protocols were obtained from the files in the National Cancer Hospital, Vietnam. The hormone receptor content in tumors from Vietnam was analyzed by immunohistochemistry (IHC) using an automated slide stainer (Bench MarkXT, Ventana). Tumors with ≥10% stained nuclei were considered as receptor positive. Tumors from Sweden were analysed with an enzyme immunoassay (EIA) with a cut-off point of ≥0.10 fmol/μg DNA as positive. We found that differences of ER/PgR positivity between Vietnamese and Swedish breast cancer patients. The ER(+) rate was higher in premenopausal but lower in postmenopausal Vietnamese patients as compared to Swedish patients (71.1% vs. 58.4%, 44.7% vs. 71.6%, respectively). The PgR(+) tumors were found in 57.8% of preand 24.7% of postmenopausal Vietnamese patients. The corresponding figure for Swedish patients was 72.9% and 65.6%, respectively. We used IHC and silver in situ hybridization (SISH) technique to assess the HER2 status for Vietnamese and compared to Swedish series with tumors analyzed by IHC and FISH. It was found that tumors from Vietnamese patients with strong, intermediate and low levels of HER2 protein expression were 39%, 11% and 50%, respectively. The concordance between IHC and SISH was 87%. Postmenopausal women were amplified in 55% as compared to 36% in premenopausal women. HER2 gene amplification occurred more often in ER(-), PgR(-) tumors and in ductal carcinomas. HER2 gene amplified rate was present in 41% of Vietnamese breast cancers and 13% in a series of Swedish breast cancers. We chose the samples from age-matched patients treated in Stockholm, Sweden. Cell proliferation in the two series was stained by anti-Ki67 antigen with an automated procedure. Ki67 index was calculated by counting stained cell nuclei in a total of 400 cells in intermediate area. No difference in distribution and mean of Ki67 indices was seen between the two series, 27.7% (± 17.1%) vs. 26.9% (±23.1%) or with respect to age, tumor size and lymph node status. Swedish patients with poor prognosticators had significantly higher Ki67 indices than Vietnamese patients, 52.8% vs. 31.9% in ER(-), 39.6% vs. 30.7% in PgR(-) and 40.1% vs. 28.3% in HER2-amplified tumors. We estimated survival by using the life-table method. The Cox model was used to determine the relationship between survival and prognostic factors and treatment. The disease-free survival rate, overall survival rate and cancer-specific survival rate in Vietnamese patients was 75.8%, 80.6%, and 86.4%, respectively at 5 years; 62.3%, 68.1%, 78.9%, respectively at 9 years. Women with poor prognostic factors had worse survival. Postmenopausal women had significantly lower survival as compared to premenopausal women as analyzed by univariate analysis (HR=0.6, 95% CI: 0.38-0.95, p=0.029), however, not by multivariate analysis (HR=0.67, 95% CI: 0.41-1.08, p=0.1). Premenopausal women had more benefit than postmenopausal patients from either endocrine treatment or chemotherapy. This thesis suggests that Vietnamese breast cancers have different tumor cell characteristics to those reported for Caucasian patients in general.