Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

Abstract

Background: Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians.

Methods: A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated.

Results: The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03) and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage) than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048). The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48) for the HER2 subtype of breast cancer.

Conclusions: The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2 detection and anti-HER2 therapy to potentially benefit a high proportion of breast cancer patients in China.

Figure 1

Double immunohistochemical staining for PR/HER2. To validate the lab staining method, commercial breast cancer tissue microarray (TMA) slides BR701 (US Biomax Inc.) were used. D1, TMA core with HER2+ and PR- staining. D2, HER2- and PR+ staining. G1, HER2+ and PR+ staining. D9, PR+ and HER2 weak-positive (borderline) staining. PR/HER2 double stains were comparable to standard single stains for HER2 and PR, although the PR signal in the double staining was somewhat weaker (original magnification: ×200).

Figure 2

Double immunofluorescence staining for ERα/ERβ. The same commercial breast cancer TMA slides were used to validate ERα staining. TMA cores C2 and C8, strong ERα nuclear staining. F10, weak ERα nuclear staining. F6, negative ERα staining. ERα fluorescent positive signals were comparable to standard single staining for ERα (original magnification: ×100).

Figure 3

Double immunofluorescence staining for ERα/ERβ using lab-constructed TMA control slides. For immunostaining quality control, lab-constructed slides were stained with each batch. One TMA core of breast tissue exhibited strong ERα and ERβ nuclear staining in tumor cells (T), other than normal epithelium (N). Most tumor cells exhibited co-expression of ERα and ERβ, as revealed in the overlapping image (original magnification: ×200).