American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer

University of Milan, Milano, Lombardy, Italy
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 06/2010; 134(6):907-22. DOI: 10.1043/1543-2165-134.6.907
Source: PubMed


To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.
The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.
Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria.
The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

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Available from: David G Hicks
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    • "Tumour grade was assigned according to Nottingham Grading System. ER and PR status were assessed on tissue microarrays (TMAs) using immunohistochemestry (IHC) with Dako (Glostrup, Denmark) ER antibody and Leica (Wetzlar, Germany) PR antibody and scored according to the American Society of Clinical Oncology and College of American Pathologists guidelines with a cutoff value of 1% positive tumour nuclei (Hammond et al, 2010). Her2 status were assessed visually using TMAs as previously described, that is, a score 3 þ is regarded as positive; 2 þ is regarded as equivocal, leading to referral for Her-2 FISH; and 0 and 1 þ are regarded as negative (Mohammed et al, 2012b). "
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    ABSTRACT: Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. Patients presenting between 1995 and 1998 were studied (n=474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14-3.09, P=0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+, CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16-5.92, P=0.020) and those who have low TSP (HR 1.98, 95% CI 1.09-3.57, P=0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35-5.36, P=0.014). Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment.British Journal of Cancer advance online publication 11 August 2015; doi:10.1038/bjc.2015.287
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    • "), cutoff definitions for the interpretation of results were modified and follow the current ASCO/CAP recommendations (Hammond et al. 2010). Since that date, at least 1 % of positively marking malignant cells is sufficient for determination of HR-status as positive. "
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    ABSTRACT: Adjuvant endocrine therapy (ET) is indicated in patients with steroid hormone receptor (HR)-positive breast cancer. The aim of this study was to evaluate the quality of HR determination and adjuvant endocrine treatment of breast cancer patients in a large cohort of more than 7000 women by analyzing data from a population-based regional cancer registry. Data from the Clinical Cancer Registry Regensburg (Bavaria, Germany) were analyzed. Female patients with primary, nonmetastatic invasive breast cancer who were diagnosed between 2000 and 2012 (n = 7421) were included. HR-status was available in 97.4 % (n = 7229) of the patients. This data set (n = 7229) was used for subsequent statistical analyses. Since 2009, almost a complete rate of 99.6 % of analyzed HR-status was achieved. In sum, 85.8 % of the patients (n = 6199) were HR-positive, whereas 14.2 % (n = 1030) were HR-negative. Overall, 85.3 % (n = 5285) of HR-positive patients received ET either alone or in combination with chemotherapy (CHT) and/or trastuzumab. The majority of premenopausal patients received CHT plus ET (716 patients, 52.3 %). In postmenopausal patients, the most frequent systemic therapy was ET alone (2670 patients, 55.3 %). Best overall survival (OS) was found in HER2-/HR-positive patients receiving CHT plus ET plus trastuzumab (7-year OS rate of 97.2 % in premenopausal patients versus 86.9 % in postmenopausal patients). Premenopausal patients had a reduced benefit from additional CHT than postmenopausal patients. Premenopausal patients receiving only ET had a 7-year OS rate of 95.3 % compared to 92.7 % of patients receiving CHT plus ET. In contrast, postmenopausal patients treated with CHT plus ET had a 7-year OS rate of 84.0 % in comparison with those patients receiving only ET with a 7-year OS rate of 81.7 %. Analysis of HR in patients with early breast cancer achieved a very high quality in recent years. The vast majority of HR-positive patients received ET, and this guideline-adherent use improved OS. Inverse effects of the CHT plus ET combination in premenopausal versus postmenopausal patients and a still existing minority of patients not receiving guideline-adherent treatment should be further investigated in future studies.
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    • "Diagnoses were made according to the recommendations of the World Health Organization classification for Tumours of the Breast (2012) and were confirmed by two experienced pathologists (HP.S., M.K.) with specific expertise in breast histopathology. All tumours were characterised as oestrogen receptor (ER) negative, progesterone receptor (PR) negative, both using a cutoff of 1% positive tumour cells (Hammond et al., 2010), and HER2 negative according to current guidelines (Wolff et al., 2007). All the cases had complete surgical resection of the primary tumour and surgical assessment of the axillary lymph nodes. "
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    ABSTRACT: Triple-negative breast cancer (TNBC) is a group of very aggressive breast tumours, characterized by lack of expression of oestrogen receptor (ER), progesterone receptor (PR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2). Nevertheless, TNBCs show different clinical characteristics and are very diverse regarding prognostic outcome. So far, only a few prognostic markers for TNBC have been reported that could be helpful for therapeutic stratification. Here we have analysed the expression of S100P and HYAL2 using immunohistochemistry (IHC) in a TNBC cohort of 98 patients with a follow-up for recurrence and death. TNBC patients with high expression of both proteins showed significantly shorter progression-free survival (PFS) (mean PFS = 35.9 months, P = 0.001) compared to TNBC patients with high expression levels of only one of the proteins (mean PFS = 69.4 months) and to TNBC patients with low expression of both proteins (mean PFS = 83.3 months). Moreover, multivariate Cox-regression model showed the combined expression of S100P and HYAL2 as independent prognostic factor for PFS (P = 0.001). The expression of S100P and HYAL2 indicated similar prognostic effect to the overall survival (OS) of TNBC patients. In addition, high expression levels of both S100P and HYAL2 showed significant association with different clinicopathological characteristics, such as more recurrence events (P = 0.004), and higher occurrence of metastasis (P = 0.002). Our study proposes S100P and HYAL2 as potential prognostic markers for TNBC. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Experimental and Molecular Pathology
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