Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

Abstract

To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 ≥ 14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies.

Correlation of Molecular Subtypes of Invasive Ductal Carcinoma of Breast with Glucose Metabolism in FDG PET/CT: Based on the Recommendations of the St. Gallen Consensus Meeting 2013

“…Over-expression of the C-erbB2 oncogene is associated with poor response to tamoxifen and other hormonal therapies, and hence, is known as a poor prognostic factor [27]. While our results revealed that the HER2(+) group has significantly higher SUVmax than the HER2(−) group (8.9 vs. 6.7 p = 0.002), many studies reported that there was no correlation between SUVmax and HER2 positivity [3, 8-10, 22, 23].…”

Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response

“…A subset of ERC tumours (around 10%) is also enriched with the HER2 receptor (Bauer et al 2010). Prior to the advent of anti-HER2 agents such as trastuzumab, patients with HER2C disease had a poorer 5-year overall survival (Nguyen et al 2008, Park et al 2012. Interestingly, although the recent HERA trial points to a similar trastuzumab response irrespective of hormone receptor status (Untch et al 2008), there is evidence that noeadjuvant trastuzumab may be less effective in ERC/ HER2C vs ERK/HER2C tumours (Bhargava et al 2011), suggesting that the presence of the ER in HER2C tumours may be an important consideration.…”

Fascin‐1 as a novel diagnostic marker of triple‐negative breast cancer

“…Histology grade was based on the Scarff‐Bloom‐Richardson system 15. According to ER, PR, HER2, and Ki‐67 status, all cases of breast cancer were categorized into four subtypes 16: luminal A (ER+ and/or PR+, HER2−, Ki‐67 < 14%), luminal B (ER+ and/or PR+, HER2−, Ki‐67 ≥ 14%; or ER+ and/or PR+, HER2+), HER2‐enriched (ER−, PR−, HER2+), and TNBC (ER−, PR−, HER2−). In cases with ER−, PR−, and HER2 2+ equivocal status, 24 underwent FISH, of whom 10 had HER2 amplification.…”