Systematic review on hormone receptor testing in breast cancer.

Assessment of hormone receptors (estrogen and progesterone) helps to direct therapy for women with breast cancer. Immunohistochemistry is most commonly used to assess hormone receptor status and it is essential that these tests are performed accurately and reliably within and across laboratories. The overall purpose of this guideline is to improve the quality and accuracy of hormone receptor testing and its utility as a prognostic and predictive marker for invasive and in situ breast cancer. Medline, EMBASE, the Cochrane Database of Systematic Reviews, and abstracts from the San Antonio Breast Cancer Symposium were searched. An environmental scan of the internet and of international guideline developers and key organizations was performed. Preanalytic elements such as the collection, fixation, and storage of samples, and analytic elements such as selection of antibodies and scoring methods that seem to offer the best results for immunohistochemical assessment of hormone receptors are presented. Proficiency testing or quality assurance of immunohistochemistry is described.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version).

PURPOSE: 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. METHODS: 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. RESULTS: 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 pre-analytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: 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.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. RECOMMENDATIONS: 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.

American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. RECOMMENDATIONS: 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.

Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline.

PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA)

Use of 5alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline.

PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA)

American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants.

PURPOSE: To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer. METHODS: An update committee reviewed literature published since the last guideline update in 2002. RESULTS: Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002. RECOMMENDATIONS: Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m(2) doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy-associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.

American Society of Clinical Oncology clinical practice guidelines: opportunities and challenges.

The American Society of Clinical Oncology (ASCO) published its first clinical practice guideline, which focused on the use of hematopoietic colony-stimulating factors, in 1994. Since then, ASCO has published 24 additional guidelines or technology assessments on a range of topics and is developing 11 additional guidelines. Guidelines are among ASCO's most valued products, according to membership surveys and data from the JCO.org Web site. However, the same data from ASCO members have highlighted a number of limitations to the guideline program. These relate to the timelines of guideline updates, difficulties locating guidelines and related products, and challenges to implementing ASCO guidelines in everyday clinical practice. This article outlines the concrete steps that the ASCO Health Services Committee (HSC) is taking to address these limitations, including the institution of a more aggressive guideline updating schedule, a transition from narrative to systematic literature reviews to support the practice recommendations, a new Board of Directors-approved policy to permit endorsement of other groups' guidelines, and a robust Clinical Tools and Resources program that offers a range of guideline dissemination and implementation aids. Additional work is underway to establish stronger and deeper collaborations with practicing oncologists to expand their role in the review, field testing, and implementation of guideline clinical tools and resources. Finally, the HSC is discussing evaluation of the guidelines program to maximize the impact of ASCO clinical practice guidelines on clinical decision making and, ultimately, the quality of cancer care.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. METHOD: An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. RECOMMENDATIONS: For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects.

PURPOSE: To review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors. METHODS: An American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006. RESULTS: Few studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans. CONCLUSION: An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

PURPOSE: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. RESULTS: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. RECOMMENDATIONS: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

PURPOSE: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2(HER2) testing in invasive breast cancer and its utility as a predictive marker. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. RESULTS: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry(IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. RECOMMENDATIONS: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3 + (uniform, intense membrane staining of 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1 +, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.