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The luminal-A-like and luminal-B-like breast cancer groups have distinct biological features that lead to differences in the treatment response and clinical outcome. The aim of this study was to examine the value of the distribution pattern of ERα expression, ESR1 SNPs as well as ESR1 mRNA expression in predicting tamoxifen response and survival in patients with luminal-A-like and luminal-B-like breast cancer. A total of 135 patients with both subtypes were stratified into two groups depending on the tamoxifen response: tamoxifen-resistant patients (TR) and tamoxifen-sensitive patients (TS). ESR1 mRNA expression was measured by real-time quantitative reverse transcription-PCR. Three polymorphisms of ESR1 (rs2077647, rs2228480 and rs1801132) were genotyped using a TaqMan assay. The distribution pattern of ERα expression was analyzed immunohistochemically using the visual assessment of staining. The primary endpoint was progression-free survival (PFS). There was a significant decrease in ESR1 mRNA expression level in the TR group when compared to the TS group among patients with luminal-B-like subtype (P = 0.038). ESR1 2014AA mutant genotype of rs2228480 was more prevalent in the TR patients with luminal-B-like subtype than the TS group (P = 0.045). In the luminal-A-like group, tamoxifen-resistant tumors were more frequently heterogeneous for ERα expression than tamoxifen-sensitive tumors (P = 0.016). Multivariate analysis showed a strong association of lymph node status and the distribution pattern of ERα expression with tamoxifen responsiveness in this cohort of patients. In addition, a luminal-A-like patients with the heterogeneous ERα expression had a significantly shorter PFS time than those with the homogeneous ERα (P = 0.013). These results indicate that the heterogeneous expression of ERα is an accurate predictor of tamoxifen response and survival in luminal-A-like breast cancer patients. ESR1 rs2228480 may act as a marker with a high prognostic potential in luminal-B-like tumors.

Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group-TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group-TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.

The aim of this retrospective study was to evaluate the objective clinical response (cOR), pathological complete response (pCR), and progression-free survival (PFS) in 231 Russian patients with four subtypes of breast cancer treated with neoadjuvant chemotherapy. About 130 (56.3 %) patients received anthracycline-based, 56 (24.2 %) capecitabine-containing (CAX), 28 (12.1 %) taxotere and 17 (7.4 %) non-anthracycline-containing chemotherapy regimens at the Tomsk Cancer Research Institute between 2000 and 2010. Tumors were subtyped according to the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) immunohistochemical data. The majority of tumors (48.9 %) were ER+/PR+ and HER2-negative (HR+/HER2-), 10.4 % were ER+ PR+ and HER2-positive (HR+/HER2+), 9.1 % were ER-/PR- and HER2-overexpressed (HER2-enriched) and 31.6 % were ER-/PR- and HER2-negative (triple negative). Both cOR and pCR were significantly higher in the triple-negative tumors compared to the other subtypes (P = 0.021 and P = 0.033, respectively). Among the four chemotherapy regimens, only CAX regimen had a predictive value for cOR (HR 2.30, 95 % CI 1.16-4.58, P = 0.009). Multivariate regression analysis showed that the triple-negative subtype (HR 2.54, 95 % CI 1.06-1.42, P = 0.011) and CAX regimen (HR 3.01, 95 % CI 1.01-1.46, P = 0.002) were significantly associated with cOR. No association between patient's PFS and a tumor subtype was observed. However, there was a trend for a prolonged PFS among patients with cOR (P = 0.056). Our data indicate a potentially better prognosis for triple-negative breast cancer patients if treated with the CAX neoadjuvant regimen.