Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12550-e12550
Author(s):  
Aimaz Afrough ◽  
Heather Lin ◽  
Angelica M. Gutierrez-Barrera ◽  
Jennifer Keating Litton ◽  
Vicente Valero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Brca Mutations ◽  
Her2 Breast Cancer

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.

scholarly journals The Effectiveness of Lapatinib in HER2-Positive Metastatic Breast Cancer Patients Pretreated With Multiline Anti-HER2 Treatment: A Retrospective Study in China

2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Xinzhao Wang ◽  
Lin Wang ◽  
Qian Yu ◽  
Zhaoyun Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival ◽  
Line Setting

Background: The aim of this study was to evaluate the effectiveness of lapatinib in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Methods: We retrospectively reviewed the medical records of patients who received lapatinib for salvage treatment at any line setting from January 1, 2007 to August 31, 2019 at Shandong Cancer Hospital and Institute. Results: A total of 115 (89.1%) patients were included in the study. In the overall cohort, the median disease-free survival (DFS) was 19.0 months; the median progression-free survival (PFS), 6.3 months; and median overall survival (OS), 88.0 months, with 32.2% of patients alive at 5 years. In the second line setting, the median PFS among trastuzumab, lapatinib, and trastuzumab plus lapatinib were 4.2 months, 5.2 months, and 7.3 months, respectively ( P = 0.004). No significant differences between the median PFSs and OSs of the different line salvage treatments with lapatinib was observed (all P > 0.05). For brain metastasis patients, the median PFSs in first line, second line, and more than 3 lines were 7.2 months, 4.5 months, and 6.3 months, respectively. Conclusions: Our findings suggest that patients would benefit more from trastuzumab plus lapatinib than from lapatinib or trastuzumab alone for second line treatment in the advanced stages of the disease. Lapatinib could be used as an alternative selection for HER2-positive metastasic breast cancer patients when there is disease progression after trastuzumab or pyrotinib treatment, which is used as part of China’s national health insurance.

scholarly journals Assessment of Survival and Cardiotoxicity of Adjuvant Trastuzumab among HER2 Breast Cancer Patients in an Oncology Centre in Malaysia

2018 ◽  
Vol 3 (1) ◽  
pp. 33
Author(s):  
Harissa Husainy Hasbullah ◽  
Anita Bustamam ◽  
Tho Lye Munn ◽  
Vincent Phua
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer

Introduction: Adjuvant trastuzumab has been used in human epidermal growth factor-2 (HER2) breast cancer to improve survival but with concern of cardiotoxicity. Our study is the first to review efficacy and toxicity of adjuvant trastuzumab in Malaysia. Methods: This is a retrospective cohort study on HER2 non metastatic breast cancer patients in University Malaya Medical Centre diagnosed between October 2006 and May 2011. Two cohorts were created based on whether or not they received adjuvant trastuzumab. Disease free survival (DFS) and overall survival (OS) for both groups were estimated using Kaplan Meier method and compared using Log rank test. Cox proportional hazards regression models analysed for potential covariates of age, tumour size and grade, node and estrogen receptor (ER) status. Trastuzumab cardiotoxicity was defined as left ventricular systolic dysfunction or heart failure with or without symptoms and graded using Common Terminology Criteria for Adverse Events (CTCAE 4.0). Results: 170 HER2 non metastatic breast cancer patients were identified. Thirty-three received trastuzumab and 136 did not. Median age was 53.4 ± 10.3 years old. Significantly more ER negative patients received trastuzumab. Four years DFS in ‘trastuzumab’ versus ‘no trastuzumab’ cohort was 90.9% vs 74.5% (p = 0.027). Four years OS was 91% vs 84.7% (p = 0.30) respectively. Majority tolerated trastuzumab with no toxicity. Five patients (15.2%) experienced cardiotoxicity (all grade I).Conclusions: Adjuvant trastuzumab significantly improved DFS in HER2 breast cancer. Treatment was well tolerated. With this we propose the justification for adjuvant trastuzumab in HER2 breast cancer in our population.

Budget impact analysis of the use of lapatinib in the treatment of breast cancer in Italy

2009 ◽  
Vol 10 (1) ◽  
pp. 33-46
Author(s):  
Francesco Bamfi ◽  
Federica Basso ◽  
Massimo Aglietta ◽  
Carmelo Bengala ◽  
Vito Lorusso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Budget Impact ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Number Of Patients ◽  
The Impact

Objective: to estimate the impact of lapatinib utilization within the Italian National Health Service (NHS) resources consumption. Lapatinib is an oral inhibitor of kinase protein, approved as dual therapy with capecitabine for the treatment of metastatic breast cancer patients with HER2 overexpression who experience disease progression despite trastuzumab treatment. Methods: the analysis is based on a model, which structure can be summarized as follows: a) national cancer registries-based estimate of the yearly number of HER2+ breast cancer patients who develop metastatic disease in Italy; b) literature-based identification of the rate of patients eligible to receive lapatinib; c) identification of the current therapeutic strategy-mix; d) costing of the alternatives, and e) calculation of budget impact. Direct NHS costs (drug acquisition and administration, and monitoring for 8 cycles of 21 days) are estimated based on current Italian prices and tariffs. Results: the annual number of patients eligible for lapatinib-based therapy can vary from 1,676 to 2,172, according to the expected extent of the trastuzumab use as adjuvant therapy. The current strategy-mix beyond progression is based on drugs used in the clinical practice, with a portion of patients continuing trastuzumab. Pharmaceutical cost of lapatinib results higher than the average cost of the current pattern of treatments. This cost increase would be partially offset by the reduction of laboratory tests and hospital personnel work for the oral administration of lapatinib, as compared to intravenous strategies. Furthermore, a risk sharing agreement has been adopted by NHS and manufacturer, according to which the NHS pays only for responding patients. As a consequence, lapatinib-based therapy would increase yearly NHS expenditure by about 3.8-4.9 millions of euro. Conclusions: lapatinib is the only treatment option specifically indicated for the management of HER2+, metastatic breast cancer in patients who received prior treatments including trastuzumab and is estimated to induce a low budget impact for the Italian NHS.

scholarly journals Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Breast Cancer ◽  
2021 ◽  
Author(s):  
Takamichi Yokoe ◽  
Sasagu Kurozumi ◽  
Kazuki Nozawa ◽  
Yukinori Ozaki ◽  
Tetsuyo Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Neratinib in HER2-Positive Breast Cancer Patients

2019 ◽  
Vol 53 (6) ◽  
pp. 612-620 ◽  
Author(s):  
Rutugandha Paranjpe ◽  
Dima Basatneh ◽  
Gabriel Tao ◽  
Carmine De Angelis ◽  
Sobia Noormohammed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Common Adverse Effect ◽  
Stage I ◽  
Phase Iii ◽  
Therapeutic Window ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Safety And Efficacy ◽  
Her2 Breast Cancer

Objective:To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib in human epidermal growth factor receptor (HER2)+ breast cancer (BC). Data Sources: A PubMed search was performed using the term neratinib between September 12, 2018, and November 21, 2018. References of published articles and reviews were also assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib were evaluated. Data Synthesis: Neratinib, an irreversible inhibitor of HER1, HER2, and HER4, is Food and Drug Administration approved for the extended adjuvant treatment of stage I-III HER2+ BC to follow trastuzumab-based therapy. A phase III study has demonstrated statistically significant improvement in 5-year disease-free survival rate (90.2 vs 87.7; hazard ratio = 0.73, 95% CI = 0.57-0.92, P = 0.0083). Its most common adverse effect is diarrhea, observed in more than 90% of patients. The incidence of grade 3/4 diarrhea (~40%) is reduced by half with loperamide prophylaxis, which is recommended for the first 8 weeks of neratinib therapy. Other common adverse reactions are nausea and fatigue. The patients need to be monitored for liver function tests and drug interactions with acid-reducing agents, CYP3A4 inhibitors/inducers, and P-glycoprotein substrates with narrow therapeutic window. Relevance to Patient Care and Clinical Practice: American Society of Clinical Oncology and National Comprehensive Cancer Network clinical guidelines suggest the use of neratinib for extended adjuvant therapy following 1-year trastuzumab in stage I to III HER2+ BC. Diarrhea remains a clinically significant but manageable adverse event. Conclusion: Neratinib significantly improves treatment outcomes and has manageable toxicity in stage I to III HER2+ BC patients.

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