METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.
RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P
METHODS: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 × 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
IMPACT: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
OBJECTIVE: This study aimed to assess the determinants of surgery choice in Asian patients with early breast cancer in a middle-income country.
MATERIALS AND METHODS: 184 patients with early breast cancer treated between Jan 2008 and Dec 2010 were recruited to complete a questionnaire. Chi-square test was used to analyze the association between surgery choice and demographic and tumour factors, surgeon recommendation, family member and partner opinions, fear of recurrence, avoidance of second surgery, fear of disfigurement, interference with sex life, fear of radiation and loss of femininity.
RESULTS: 85 (46%) had BCS while 99 (54%) had mastectomy. Age >60, Chinese ethnicity, lower education level, and larger tumour size were significantly associated with mastectomy. Surgeon recommendation was important in surgery choice. Although both groups did not place much importance on interference with sex life, 14.1% of the BCS group felt it was very important compared to 5.1% in the mastectomy group and this was statistically significant. There was no statistical difference between the two groups in terms of the other factors. When analyzed by ethnicity, significantly more Malay and Indian women considered partner and family member opinions very important and were more concerned about loss of femininity compared to Chinese women. There were no statistical differences between the three ethnic groups in terms of the other factors.
CONCLUSIONS: When counseling on surgical options, the surgeon has to take into account the ethnicity, social background and education level, age and reliance on partner and family members. Decision-making is usually a collective effort rather than just between the patient and surgeon, and involving the whole family into the process early is important.
METHODS: Two prospective groups of 423 and 965 newly diagnosed breast cancer patients in University of Malaya Medical Centre, Kuala Lumpur, Malaysia diagnosed in two time periods ie. 1993 to 1997 and in 1998 to 2002 were studied. Vital status was obtained from the National Registry of Births and Deaths. The overall survival was calculated from the date of diagnosis to the date of death from any cause. The survival differences between the two groups were analysed using the log-rank or Peto-Wilcoxon method. Survival estimates and independent prognostic factors were estimated by the Kaplan-Meier method and multivariate analysis using Cox proportional hazard models. P values less than 0.05 were considered statistically significant. Analyses were performed using SPlus 2000 Professional Release 2.
RESULTS AND DISCUSSION: Median follow-up for the two groups were 55 months (SD 29.2 months) in the first group and 52 months (SD 24.43) in the second group. There was improvement in 5-year observed survival from 58.4% (CI 0.54-0.63) to 75.7% (CI 0.73-0.79). The improvement in survival was significantly seen in all co-variates (p< 0.05) except for those aged 40 years and below (p= 0.27), tumour size 2 to 5 cm (p=0.11), grade 3 (p=0.32) and patients with Stage IV disease (p= 0.80). Stage of disease, lymph node (LN) involvement, size and grade were identified as independent prognostic factors in cohort one. For the second cohort; stage and LN involvement remained independent factors with the addition of ER status and ethnicity.
CONCLUSIONS: There was improvement in 5-year observed survival. Besides known prognostic factors, Malay ethnicity was an independent prognostic factor.
METHODS: We studied 522 patients who underwent mastectomy between 1998 and 2002 and followed them up until 2008. We defined PMLRR as recurrence to the axilla, supraclavicular nodes and or chest wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors for locoregional recurrence were determined using the Cox proportional hazards regression model.
RESULTS: The overall PMLRR rate was 16.4%. ILR developed in 42 of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained disease free after treatment while 17 (40.5%) suffered disease progression. Univariate analyses identified race, age, size, stage, margin involvement, lymph node involvement, grade, lymphovascular invasion and ER status as probable prognostic factors for ILR. Cox regression resulted in only stage III disease and margin involvement as independent prognostic factors. The hazard of ILR was 2.5 times higher when the margins were involved compared to when they were clear (aHRR 2.5; 95% CI 1.3 to 5.0). Similarly, compared with stage I those with Stage II (aHRR 2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse prognosis for ILR.
CONCLUSION: Margin involvement and stage III disease were identified to be independent prognostic factors for ILR. Close follow-up of high risk patients and prompt treatment of locoregional recurrence were recommended.
METHODS: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors.
RESULTS: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy.
CONCLUSION: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.
OBJECTIVE: To evaluate the association between clinico-pathological features and HER2 overexpression in breast cancer.
METHODS: This is a retrospective study conducted in the Department of Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined by immunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosed breast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression.
RESULTS: HER2 overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely related to ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumour grade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2 overexpression was significantly associated with higher tumour grade (p= 0.018, CI 1.25-11.04), PR negativity (p= 0.002, CI 0.30-0.77) and lymphovascular positivity (p= 0.042, CI 1.01-2.12).
CONCLUSIONS: HER2 overexpression was observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a more aggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. No significant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathology subtype and stage of disease from this study.