Elizabeth Tan-Chiu

Bio: Elizabeth Tan-Chiu is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Breast cancer & Metastatic breast cancer. The author has an hindex of 19, co-authored 38 publications receiving 10704 citations. Previous affiliations of Elizabeth Tan-Chiu include University of North Florida & Allegheny College.

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer

Abstract: Background We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. Methods The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclit...

Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or Without Trastuzumab As Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer: NSABP B-31

Abstract: Purpose Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) –positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. Patients and Methods National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. R...

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

Abstract: Purpose The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2) –overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population. Patients and Methods This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy. Results With a follow-up of ≥ 12 months among 112 treated patients, the objecti...

erbB-2 and Response to Doxorubicin in Patients With Axillary Lymph Node-Positive, Hormone Receptor- Negative Breast Cancer

Abstract: Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors-DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.44-0.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P =.01 ; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44-0.85), P = .003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.79-1.35), P = .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06). Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma.

Abstract: BACKGROUND This report is an 8-year update of the authors' previous findings from National Surgical Adjuvant Breast Project (NSABP) Protocol B-17, which relates to the influence of pathologic characteristics on the natural history and treatment of intraductal carcinoma (DCIS). METHODS Nine pathologic features observed in a pathologic subset of 623 of 814 evaluable women enrolled in this randomized clinical trial were assessed for their role in the prediction of second ipsilateral breast tumors (IBT), other events, and selection of breast irradiation (XRT) following lumpectomy. RESULTS The frequency of subsequent IBT was reduced from 31% to 13% (P = 0.0001) by XRT. The average annual hazard rates for IBT were reduced by XRT for all pathologic features examined. Four characteristics were individually noted to be significantly related to IBT, but only moderate-to-marked and absent-to-slight comedo necrosis were found to be independent high and low risk predictors, respectively, for such an event in patients of both treatment groups. XRT effected a 7% absolute reduction at 8 years in the low risk group. Despite a relatively high incidence (≈40%) of IBT consisting of invasive cancer, mortality due to breast carcinoma after DCIS for the entire cohort was found to be only 1.6% at 8 years. CONCLUSIONS The degree of comedo necrosis in patients with DCIS appears to be sufficient for discriminating between high and low risks for IBT following lumpectomy for DCIS. Although margin status, unlike in our previous report, was found to have only a slight or borderline influence on the frequency of IBT at 8 years, excision of DCIS with free margins is advised. The low risk group exhibits a statistically significant reduction of IBT from XRT. The decision to forgo XRT in the treatment of this singular subset of patients would appear to depend on clinical considerations and the input of informed patients rather than being standard practice. [See editorial on pages 375–7, this issue.] Cancer 1999;86:429–38. © 1999 American Cancer Society.

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer

Abstract: Background We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. Methods The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclit...

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer

Abstract: background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)

American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer

Abstract: 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...

Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer

Abstract: A b s t r ac t The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. Conclusions Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2- positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572.)