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Caroline Lohrisch

Bio: Caroline Lohrisch is an academic researcher from University of British Columbia. The author has contributed to research in topics: Breast cancer & Medicine. The author has an hindex of 14, co-authored 40 publications receiving 5624 citations. Previous affiliations of Caroline Lohrisch include European Organisation for Research and Treatment of Cancer.


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Journal ArticleDOI
TL;DR: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with 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.)

4,815 citations

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TL;DR: Exemestane is well tolerated and active in the first-line treatment of hormone-responsive MBC, and an ongoing EORTC phase III trial is comparing the efficacy, measuring time-to-disease progression, of exemstane and tamoxifen.

221 citations

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TL;DR: No differences in the efficacy study end points were observed between the two treatment arms, and treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen.
Abstract: PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m2 as an intravenous bolus plus paclitaxel 175 mg/m2 as a 3-hour infusion) or AC (doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m2) and cyclophosphamide (750 mg/m2) dose escalation was planned at cycle 2 if no grade ≥ 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. T...

215 citations

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TL;DR: It is demonstrated that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials.
Abstract: Purpose: Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% of breast cancers, as well as pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications of HRD signatures. Whereas BRCA1/2 mutations confer sensitivity to platinum-based chemotherapies, it is not yet clear whether mutation signatures can independently predict platinum response. Experimental Design: In this observational study, we sequenced tumor whole genomes (100× depth) and matched normals (60×) of 93 advanced-stage breast cancers (33 platinum-treated). We computed a published metric called HRDetect, independently trained to predict BRCA1/2 status, and assessed its capacity to predict outcomes on platinum-based chemotherapies. Clinical endpoints were overall survival (OS), total duration on platinum-based therapy (TDT), and radiographic evidence of clinical improvement (CI). Results: HRDetect predicted BRCA1/2 status with an area under the curve (AUC) of 0.94 and optimal threshold of 0.7. Elevated HRDetect was also significantly associated with CI on platinum-based therapy (AUC = 0.89; P = 0.006) with the same optimal threshold, even after adjusting for BRCA1/2 mutation status and treatment timing. HRDetect scores over 0.7 were associated with a 3-month extended median TDT (P = 0.0003) and 1.3-year extended median OS (P = 0.04). Conclusions: Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials. Clin Cancer Res; 23(24); 7521–30. ©2017 AACR.

127 citations

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TL;DR: The two-fold risk of relapse and breast cancer death associated with high-risk medial breast tumors may be due to occult spread to internal mammary nodes (IMNs).
Abstract: PURPOSE: To explore the independent prognostic impact of medial hemisphere tumor location in early breast cancer. PATIENTS AND METHODS: A comprehensive database was used to review patients referred to the British Columbia Cancer Agency from 1989 to 1995 with early breast cancer. Patients were grouped according to relapse risk (high or nonhigh) and adjuvant systemic therapy received. Multiple regression analysis was used to determine whether the significance of primary tumor location (medial v lateral hemisphere) was independent of known prognostic factors and treatment. RESULTS: In the adjuvant systemic therapy groups, medial location was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral location. Five-year systemic disease-free survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (P < .005). Corresponding 5-year disease-specific survival rates were 75.7% and 80.8%, respectively (P < .03). No significant differences we...

121 citations


Cited by
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TL;DR: A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed and strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored.
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...

4,560 citations

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TL;DR: Broad treatment recommendations are presented, recognizing that detailed treatment decisions need to consider disease extent, host factors, patient preferences, and social and economic constraints.

3,160 citations

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TL;DR: Lapatinib plus capecitabine is superior to cape citabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab.
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.)

3,149 citations

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TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.

2,831 citations