Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience

BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.

Reproducibility of the Nottingham modification of the Scarff- Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system

Background The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson （NSBR） histological grading system for invasive breast cancer （IBC） adopted by the World Health Organization （WHO） has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system.Methods Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index （Ki-67LI） was determined by immunohistochemistry, and its correlations with histological grade and survival were determined.Results With respect to interobserver reproducibility, NSBR grading was fairly reproducible （kappa=0.34）; as for the components of NSBR grading, agreement was best for tubule formation （kappa=0.46）, intermediate for nuclear pleomorphism （kappa=0.42）, and poorest for mitotic count （kappa=0.28）. In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading （kappa=0.30-0.69） and nuclear pleomorphism （kappa=0.28-0.69）, moderate to substantial for tubule formation （kappa=0.51-0.78）, and slight to substantial for mitotic count （kappa=0.19-0.71）.There were characteristic Ki-67LI ranges for grades 1,2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival.Conclusions The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate grading and treatment for IBC. Ki-67, with proven prognostic significance, adds complementary value to the NSBR system.