Onitilo AA, Engel JM, Greenlee RT, Mukesh BNBreast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7: 4-13

Department of Hematology/Oncology, Marshfield Clinic Weston Center, Weston, Wisconsin 54401, USA.
Clinical Medicine & Research 07/2009; 7(1-2):4-13. DOI: 10.3121/cmr.2009.825
Source: PubMed


To compare the clinicopathologic features and survival in the four breast cancer subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2-; ER/PR-, Her2+; and ER/PR-, Her2-.
A 7-year retrospective study of 1134 invasive breast cancer subjects. Clinical and pathologic features and survival of the four subtypes were compared.
Using ER/PR+ and Her2- as a reference, ER/PR-, Her2- had the worst overall survival (hazard ratio, 1.8; 95% confidence interval [CI], 1.06-3.2) and the worst disease-free survival (hazard ratio, 1.5; 95% CI, 0.8-3.0). In ER/PR+, Her2-, chemotherapy conferred significant overall and disease-free survival advantages. Subtype comparison revealed statistically significant differences in outcomes.
The triple negative subtype has the worst overall and disease free survival. Efforts should be directed at standardization of current testing methods and development of more reliable and reproducible testing.

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    • "The gene expression profile revealed that the levels of Estrogen (ER), Progesterone (PR) hormone receptors (HR) and HER2 overexpression characterize tumors of different subtypes, including Luminal A (ER + and/or PR + and HER2-), Luminal B (ER + and/or PR + and HER2+), HER2 overexpressed (ER- PR- HER2+) and triple negative (TN; ER- PR- HER2-) breast cancer [2-5]. Subtypes have different prognostic values, and Luminal A and triple negative tumors show the best and worst outcomes, respectively [6-9]. "
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    ABSTRACT: Background The frequencies of molecular breast cancer subtypes vary among different human populations. The Northeastern region of Brazil has a mixed population of African, Indigenous and European ancestry. This retrospective study investigated breast cancer subtypes and applied therapies in a public hospital of Northeastern Brazil. Methods Data of 633 patients with invasive breast cancer from 2005 to 2011 were obtained from medical records. Status of hormone receptor (HR), HER2 and Ki67 expression index of 269 out of 633 patients were used to define subtypes of Luminal A and B, HER2 and triple negative (TN) breast cancer. Expression index of Ki67 ≥ 14% was applied to distinguish Luminal A from Luminal B subtypes. Results Overall, 185 (68.77%) and 132 (49.07%) patients showed positive hormone receptor (HR+) and positive HER2 (HER2+) tumors. The mean age ranged from 53.33 to 58.25 years for patients with tumors of Luminal B and Luminal A subtypes, respectively (p = 0.0182). In general, 67.39% of patients with TN tumors aged over 50 and 19.57% aged between 31 and 40 years (p = 0.0046). The rate of small tumors (T1: ≤ 2.0 cm) varied from 22.73% to 52.46% for TN and Luminal A subtypes (p = 0.0088). The rate of high graded (G3) tumors was increased for HER2 and TN subtypes (35.29% and 34.28%) compared to Luminal A and Luminal B subtypes (3.92% and 12.62%), respectively (p < 0.0001). The five-year survival rate ranged from 92.86% to 75.00%, for Luminal A, HER2 and TN subtypes, respectively (HR: 0.260 to 1.015; 95% CI: 0.043 to 3.594; p = 0.2589). Patients with HER2 positive (HER2+) breast tumors did not receive immunotherapy and chemotherapy application varied from 54.84% to 86.49% for Luminal A and HER2 subtypes, respectively (p = 0.0131). Conclusions The results of this study revealed a high percentage of HER2+ breast tumors and an increased rate of patients with TN tumors aged over 50 years. This emphasizes the need for establishing immunotherapy as an additional therapeutic option to improve clinical outcomes for patients with HER2+ tumors and to investigate the risk factors of TN breast cancer.
    Full-text · Article · Sep 2014 · BMC Women's Health
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    • "Treatment of the basal-like class is currently based on cytotoxic drugs and have a worse overall and disease-free survival [2,4]. A small subclass, referred to as the special histological types (being medullary and adenoid cystic carcinomas) can still be eligible to endocrine treatment [2]. "
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    ABSTRACT: The most commonly used biomarkers to predict the response of breast cancer patients to therapy are the oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specific therapies such as endocrine treatment in the event of ER and PgR positivity, and the monoclonal antibody, trastuzumab, in the case of HER2-positive patients. Patients who are negative for these three biomarkers, the so-called triple negatives, however, derive little benefit from such therapies and are associated with a worse prognosis. Deregulation of the protein serine/threonine phosphatase type 2A (PP2A) and its regulatory subunits is a common event in breast cancer, providing a possible target for therapy. The data portal, cBioPortal for Cancer Genomics was used to investigate the incidence of conditions that are associated with low phosphatase activity. Four (4) adherent human breast cancer cell lines, MDA-MB-468, MDA-MB-436, Hs578T and BT-20 were cultured to assess their viability when exposed to various dosages of rapamycin or FTY720. In addition, RNA was extracted and cDNA was synthesised to amplify the coding sequence of PPP2CA. Amplification was followed by high-resolution melting to identify variations.Results and conclusion: The sequence of PPP2CA was found to be conserved across a diverse panel of solid tumour and haematological cell lines, suggesting that low expression of PPP2CA and differential binding of inhibitory PPP2CA regulators are the main mechanisms of PP2A deregulation. Interestingly, the cBioPortal for Cancer Genomics shows that PP2A is deregulated in 59.6% of basal breast tumours. Viability assays performed to determine the sensitivity of a panel of breast cancer cell lines to FTY720, a PP2A activator, indicated that cell lines associated with ER loss are sensitive to lower doses of FTY720. The subset of patients with suppressed PP2A activity ispotentially eligible for treatment using therapies which target the PI3K/AKT/mTOR pathway, such as phosphatase activators. Full text Access:
    Full-text · Article · Jan 2014
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    • "However, all of these are postoperative factors. In addition, though certain abnormal tumor-associated genetic molecules were identified as being able to predict the prognosis of the patients (5,6), their measurement is to a certain extent time-consuming and complex and frequently not integrated into clinical practice. Therefore, identifying pre-treatment prognostic factors, including a number of serum biomarkers, would offer the opportunity for more objective and reproducible measurement and risk stratification prior to surgery. "
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    ABSTRACT: Elevated levels of C-reactive protein (CRP) have been described as a prognostic factor in various types of human malignancy. In the present study, the prognostic potency of CRP was validated for patients with colorectal cancer (CRC) in order to guide patient management and define high-risk populations for follow-up or for therapeutic purposes. The association between the high sensitivity-CRP (hs-CRP) levels of a total of 123 patients with CRC and their clinicopathological characteristics was explored. Subsequently, univariate and multivariate analyses were performed to investigate the survival impact of pre-treatment hs-CRP levels in this cohort study. Statistically significant correlations between the serum levels of hs-CRP and lymph node and distant metastasis (P<0.001 and P=0.012, respectively), vascular and perineural invasion (P<0.001 and P<0.001), grades (P=0.022) and clinical stages (P=0.001), but not age and gender (P=0.616 and 0.676, respectively), were found. The five-year survival rate of patients with elevated (>5.0 mg/l) hs-CRP levels was demonstrated to be significantly less than that of those in the normal group (≥5.0 mg/l) by applying the Kaplan-Meier method (13.3 versus 57.0%, log-rank test P<0.001). Furthermore, following identification as a prognostic factor through using univariate analysis, high levels of hs-CRP (P<0.001) were validated as an independent prognosticator in CRC in the present study through using multivariate analysis. Pre-treatment serum CRP levels were associated with advanced and progressed CRC patients, therefore these levels may serve as a potential prognostic marker for CRC patients.
    Full-text · Article · Dec 2013 · Experimental and therapeutic medicine
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