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Edith A Perez

Publications and source records attributed to Edith A Perez.

At least 19 recordsLinked to original sources
PubMed2026

Profiling Dectin-2-Positive Tumor-Associated Macrophages Across Human Cancers by Immunohistochemistry.

PURPOSE: To characterize the prevalence and distribution of Dectin-2-positive macrophages across human tumors and develop a research immunohistochemistry (IHC) assay to assess Dectin-2 in cancer tissues. MATERIALS AND METHODS: C-type lectin domain family 6 member A (CLEC6A), the gene encoding Dectin-2, was evaluated across 38 tumor types using The Cancer Genome Atlas. A fit-for-purpose Dectin-2 IHC assay was developed using a monoclonal antibody selected from screening 11 anti-Dectin-2 antibodies. Assay performance was supported by Dectin-2-expressing and parental cell line controls, macrophage-associated staining patterns, and comparison with an orthogonal CLEC6A in situ hybridization method using RNAscope. Dectin-2 expression was assessed in tissue microarrays (n = 553 samples) across 6 cancer types and whole tissue sections (n = 137) across 7 cancer types. RESULTS: The Cancer Genome Atlas analysis identified enriched CLEC6A expression in several tumor types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and subsets of head and neck cancer (HNC) and colorectal cancer (CRC). By IHC, Dectin-2-positive macrophages were detected across tumor types, with notable heterogeneity within and across cancer types. In tissue microarrays, NSCLC showed the highest frequency of Dectin-2-positive macrophage infiltration, with 38% of cases with staining ≥1% of tumor area. Whole tissue section analysis confirmed and expanded these findings, with ≥50% of NSCLC, melanoma, HNC, TNBC, and CRC samples showing Dectin-2-positive macrophages in ≥1% tumor area. CONCLUSIONS: Dectin-2 expression was observed in subsets of tumor-associated macrophages across multiple human cancers, with relatively enriched expression in NSCLC, melanoma, HNC, TNBC, and CRC. To our knowledge, this study represents the first broad protein-level characterization of Dectin-2 across multiple human tumor types, identifies cancers with relatively enriched Dectin-2-positive macrophage infiltration, and provides a foundation for future translational studies of Dectin-2-targeted therapies.

Humans↗
PubMed2006

Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer.

PURPOSE: Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss. PATIENTS AND METHODS: Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than -2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12. RESULTS: The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P < .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P < .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P < .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P < .0001), respectively. CONCLUSION: With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.

Adult↗
PubMed2006

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.

Female↗
PubMed2006

The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen.

BACKGROUND: Tamoxifen is biotransformed to the potent anti-estrogen, endoxifen, by the cytochrome P450 (CYP) 2D6 enzyme. CYP2D6 genetic variation and inhibitors of the enzyme markedly reduce endoxifen plasma concentrations in tamoxifen-treated patients. Using a North Central Cancer Treatment Group adjuvant tamoxifen trial, we performed a comprehensive evaluation of CYP2D6 metabolism by assessing the combined effect of genetic variation and inhibition of the enzyme system on breast cancer recurrence and death. METHODS: Medical records were reviewed at each randomizing site to determine whether CYP2D6 inhibitors were co-prescribed with tamoxifen. Extensive metabolizers were defined as patients without a *4 allele (i.e., wt/wt) who were not co-prescribed a CYP2D6 inhibitor. Patients with decreased CYP2D6 metabolism were classified as intermediate or poor metabolizers (PM) based on the presence of one or two CYP2D6*4 alleles or the co-administration of a moderate or potent CYP2D6 inhibitor. The association between CYP2D6 metabolism and clinical outcome was assessed using Cox modeling. RESULTS: Medication history was available in 225/256 eligible patients and CYP2D6*4 genotype in 190 patients. Thirteen patients (6%) were co-prescribed a CYP2D6 inhibitor [potent (n = 3), moderate (n = 10)], resulting in the following CYP2D6 metabolism: extensive (n = 115) and decreased (n = 65). In the multivariate analysis, patients with decreased metabolism had significantly shorter time to recurrence (p = 0.034; adj HR = 1.91; 95% CI 1.05-3.45) and worse relapse-free survival (RFS) (p = 0.017; adj HR = 1.74; 1.10-2.74); relative to patients with extensive metabolism. Cox' modeling demonstrated that compared to extensive metabolizers, PM had the most significant risk of breast cancer relapse (HR 3.12, p = 0.007). CONCLUSION: CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer. Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women.

Adult↗
PubMed2006

Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17.

PURPOSE: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. PATIENTS AND METHODS: Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. RESULTS: Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81% < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6% v -0.71%; P = .044) and lumbar spine BMD (-5.35% v -0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). CONCLUSION: After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.

Adult↗
PubMed2006

HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial.

PURPOSE: To evaluate concordance between local and central laboratory HER2 testing results in patients from the North Central Cancer Treatment Group (NCCTG) N9831 adjuvant trial of trastuzumab. PATIENTS AND METHODS: NCCTG N9831 is a randomized, phase III clinical trial comparing three drug regimens: doxorubicin/cyclophosphamide followed by paclitaxel with trastuzumab added concurrently, sequentially, or not at all as adjuvant therapy for women with HER2-positive resected breast cancer. Originally, patients were eligible if their tumors were HER2 positive by either local laboratory immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). A protocol modification in 2002 made central laboratory testing mandatory, with additional testing of discordant cases conducted by a reference laboratory. Concordance between local and central laboratory, and level of agreement between central and reference laboratory HER2 findings in discordant cases were examined. RESULTS: HER2 positivity was confirmed in 85.8% of 2,535 patients registered since March 2002. When local and central evaluation used the same methodology, concordance was 88.1% for FISH and 81.6% for a diagnostic test for presence of the HER2 protein. Among discordant cases examined at the reference laboratory, there was 94.3% agreement for IHC (0, 1+, 2+) and 95.2% agreement for FISH (not gene amplified). CONCLUSION: There was a high degree of discordance between local and central testing for IHC and FISH, but a high degree of agreement between central and reference laboratories. These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy.

Antibodies, Monoclonal↗
PubMed2006

Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer.

CONTEXT: Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. OBJECTIVE: To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. DESIGN, SETTING, AND PATIENTS: Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. MAIN OUTCOME MEASURES: Disease-free and overall survival. RESULTS: For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. CONCLUSION: Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen.

PURPOSE: In the adjuvant treatment of estrogen receptor (ER)-positive breast cancer, additional markers are needed to identify women at high risk for recurrence. EXPERIMENTAL DESIGN: We examined the association between the ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial (NCCTG 89-30-52). RESULTS: Tumor blocks were obtained from 211 of 256 eligible patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients. The cut point for the two-gene log 2(expression ratio) that best discriminated clinical outcome (recurrence and survival) was selected and identified women with significantly worse relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS), independent of standard prognostic markers. The cut point differed as a function of nodal status [node negative (59th percentile) versus node positive (90th percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was not associated with relapse or survival. In contrast, in the node-negative cohort (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [hazard ratio (HR), 1.98; P = 0.031], DFS (HR, 2.03; P = 0.015), and OS (HR, 2.4; P = 0.014), independent of standard prognostic markers. CONCLUSION: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied.

Adult↗
PubMed2006

Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial.

PURPOSE: MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. METHODS: The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. RESULTS: Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p < 0.0001 and p = 0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p = 0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p = 0.027) whereas the HRs for DDFS and OS showed no significant change over time. CONCLUSION: These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.

Aged↗
PubMed2006

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52.

PURPOSE: This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease. PATIENTS AND METHODS: Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause. RESULTS: There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64-1.10) and that for death was 0.89 (95% CI: 0.67-1.18). As expected there was more virilization in women who received Flu. CONCLUSIONS: This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.

Adult↗
PubMed2006

Fulvestrant in women with advanced breast cancer after progression on prior aromatase inhibitor therapy: North Central Cancer Treatment Group Trial N0032.

PURPOSE: Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. This study was designed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor (AI). PATIENTS AND METHODS: A one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and, at most, one additional hormonal agent. Tumors must have been estrogen receptor and/or progesterone receptor positive. The primary end point was objective response rate, and secondary end points were time to disease progression, survival, duration of response, and toxicity. RESULTS: Eighty patients were enrolled, and three were ineligible. Characteristics of the 77 eligible patients included median age of 68 years, performance score of 0 or 1 in 91% of patients, visceral dominant disease in 88% of patients, two prior hormonal treatments in 73% of patients, and prior chemotherapy for metastatic disease in 32% of patients. Eleven patients (14.3%) achieved a partial response, and 16 patients (20.8%) had stable disease for at least 6 months, for a clinical benefit rate of 35%. Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen. Median time to progression was 3 months, and median survival time was 20.2 months. Fulvestrant was well tolerated. CONCLUSION: Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.

Aged↗
PubMed2006

New therapies in the treatment of breast cancer.

Systemic therapy for breast cancer is undergoing many interesting advances. In recent years, a better understanding of the underlying biology of cancer has led to the identification of several opportunities to target cellular pathways for therapeutic advantage. Hormonal therapy is often chosen as the first line of therapy because it is generally very well tolerated. However, most patients eventually become unresponsive to endocrine manipulation. Improved understanding of the mechanisms of hormonal resistance, and of the interplay between hormone receptors and cellular growth pathways, provides the rationale for combining signal transduction inhibitors and hormonal agents to overcome resistance. Emerging data from preclinical studies suggest that this goal might be achievable in the clinic. Antiangiogenic therapy has shown efficacy in colorectal and lung cancer and appears promising in breast cancer, although improved overall survival has not yet been shown. There have also been advances in cytotoxic chemotherapy. Reformulation of paclitaxel in polyoxy-castor-oil-free albumin nanoparticles (ABI-007) has allowed more convenient, safer, and enhanced drug delivery with associated improvement in outcomes. New agents with novel mechanisms of action are also in development and appear to have activity in cancer cells that are resistant to currently available agents.

Angiogenesis Inhibitors↗
PubMed2006

Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer.

Up to one fourth of women diagnosed with early breast cancer (EBC) have tumors that are human epidermal growth factor receptor 2 (HER-2) positive. This is associated with a high risk of relapse and death from meta-static disease. Trastuzumab, a monoclonal antibody directed against the extracellular domain of HER-2, improves survival and quality of life in women with HER-2-positive metastatic breast cancer receiving chemotherapy. Four major adjuvant trials-Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006-including between them >13,000 women with HER-2-positive EBC, have investigated different adjuvant treatment approaches with trastuzumab. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about half in this population. The benefit was similar across the trials despite differences in patient populations, chemotherapy regimens, and sequencing of treatment. At a 2-year follow-up, interim results from the combined analysis of the NSABP B-31 and NCCTG N9831 trials showed a one third lower mortality for trastuzumab, and there was a trend toward an overall survival benefit in the HERA and BCIRG trials. A small Finnish trial, FinHer, investigating another regimen of trastuzumab, has also shown similarly positive results. Further follow-up of the major adjuvant trials will clarify the survival benefit for women receiving trastuzumab, as well as the optimal treatment duration (1 or 2 years). Notably, cardiac events in the trastuzumab-containing arms of these trials have remained within acceptable levels, with a slightly higher (0.6%-3.3%) incidence of congestive heart failure that mostly responded to treatment. Further follow-up will provide information on long-term cardiac safety. Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies.

Antibodies, Monoclonal↗
PubMed2006

Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients with breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed-care population of women with breast cancer. PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tamoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an AI (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7% in the AI group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the AI group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the AI group than in the non-AI group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. CONCLUSION: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an AI for breast cancer.

Aged↗
PubMed2006

NCCN Task Force Report: Adjuvant Therapy for Breast Cancer.

The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

Adult↗
PubMed2006

Advances in adjuvant therapy for breast cancer.

The development of adjuvant therapy has made a significant positive impact on clinical outcomes for patients with breast cancer. Over the past 30 years the field of adjuvant therapy has evolved from its cyclophosphamide/methotrexate/5-fluorouracil beginnings by adding new agents and modifying treatment schedules and dosing. More recently, the application of targeted therapies based on hormone receptor status and HER2 expression is providing a new level of efficacy for these patients. The biologic agent trastuzumab, a monoclonal antibody directed against HER2, first demonstrated significant activity in patients with metastatic breast cancer, reducing the risk of death by 30%. The agent was then evaluated in an adjuvant setting in several large trials. In a recently published joint efficacy analysis, the addition of trastuzumab to standard adjuvant chemotherapy regimens led to a 52% reduction in events (ie, recurrent cancer, second primary cancer, or death before recurrence) and a significant improvement in overall survival. These dramatic findings highlight the need for accurate HER2 testing to best identify the HER2(+) patients who would benefit from the treatment. Currently there is some debate about how to best approach HER2 testing: with the protein-based immunohistochemistry or the genetic-based fluorescence in situ hybridization. Current research evaluating the different techniques may help to settle this question. Finally, new targeted agents are being investigated and ongoing research aims to identify additional potential therapeutic targets to further improve outcomes for these patients.

Angiogenesis Inhibitors↗
PubMed2006

HER2 testing in breast cancer: NCCN Task Force report and recommendations.

The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

Advisory Committees↗