scholarly journals Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer

2014 ◽  
Vol 48 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Tanja Marinko ◽  
Jure Dolenc ◽  
Cvetka Bilban-Jakopin
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Left Breast ◽  
Thoracic Wall ◽  
Breast Cancer Patients ◽  
Long Term Effects ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

AbstractBackground. Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too.Conclusions. Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance.

scholarly journals Suboptimal Therapy Following Breast Conserving Surgery in Triple Negative and HER2-Postive Breast Cancer Patients

2021 ◽  
Author(s):  
Jeffrey E. Johnson ◽  
Paula D Strassle ◽  
Guilherme C de Oliveira ◽  
Chris B. Agala ◽  
Philip M. Spanheimer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Systemic Therapy ◽  
Triple Negative ◽  
Early Stage ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Optimal Therapy ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Purpose To assess potential disparities in guideline-concordant care delivery among women with early stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. Methods Women ≥40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. Results 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5-years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82). Conclusion Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.

Increased FoxP3 and PD-L1 in non-pCR tissue from early stage HER2 positive breast cancer patients treated with trastuzumab-pertuzumab based regimens.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 602-602
Author(s):  
Jeremy Meyer Force ◽  
Lynn Jackson Howie ◽  
Sara Abbott ◽  
Rex C. Bentley ◽  
Paul K. Marcom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Tumor mutation burden and PIK3CA mutations are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12610-e12610
Author(s):  
Qiyun Shi ◽  
Juncheng Xuhong ◽  
Jia Ge ◽  
Feng Liu ◽  
Yang Lan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Mutation Burden ◽  
Positive Breast Cancer

e12610 Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods: To date, a total of 96 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results: Among the cohort of 96 cases, a total of 32 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 18 of them achieved total pCR. The most frequently mutated driver genes were TP53 (75%), PIK3CA (44%), NBN (9%), RUNX1 (9%), FANCD2 (9%), ATRX (9%), MAP3K1 (9%) and NF1 (9%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (63%), MYC (22%), CCND1 (19%), CDK12 (16%) and FGF19 (16%), respectively. The median tumor mutation burden (TMB) of the 36 patients was 4.23 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had significantly higher median TMB (5.29 vs 3.17 mut/Mb, P = 0.025). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (88.9% vs 14.3%, P < 0.001). Conclusions: Preliminary results suggested that HER2-positive breast cancer patients with higher TMB and activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. *Qiyun Shi and Juncheng Xuhong contributed equally. #Co-corresponding author (Dr. Jun Jiang, [email protected]; Dr. Xiaowei Qi, [email protected]). Clinical trial information: ChiCTR1900022293.

Correlation between mutation landscape and clinical outcomes of neoadjuvant therapy in HER2-positive breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 579-579
Author(s):  
Ning Liao ◽  
Yulei Wang ◽  
Kai Li ◽  
Bo Chen ◽  
Guo-Chun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Early Stage ◽  
Pathologic Response ◽  
Stage I ◽  
Missense Mutations ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

579 Background: The standard management of early stage human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer (BC) involves neoadjuvant therapy with combination of chemotherapy and HER2-targeted therapy followed by surgery. However, diverse pathologic responses were observed. We interrogated whether baseline genomic heterogeneity contributes to the varied therapeutic responses. Methods: Capture-based targeted sequencing using a panel consisting of 520 cancer-related genes, spanning 1.6MB of human genome, was performed on tissue biopsy samples, obtained prior to neoadjuvant therapy, of 33 HER2+ women with stage I-III BC. The median age of the cohort was 53. The correlation between genomic alterations and pathologic response were analyzed by multivariate analysis. Results: A majority of them was diagnosed with stage II (67%, 22/33), while 30% (10/33) had stage III and 3% (1/33) had stage I disease. 58% (19/33) were HR+ and 42% (14/33) were HR-. Mutation profiling of baseline samples revealed 349 mutations spanning 145 genes, with TP53, CDK12 and PIK3CA being the top 3 most frequently mutated genes. Neoadjuvant regimen was comprised of trastuzumab and HER2 inhibitor (i.e. pertuzumab or lapatinib). 15 patients used single HER2 inhibitor;18 used dual HER2 inhibitors. Endocrine therapy was also administered to HR+ patients (19/33) in combination with trastuzumab and HER2 inhibitor. Complete pathologic response (pCR) was observed in 45.5% (15/33) of patients. Interestingly, ROS1 copy number amplifications (CANs) were only identified in patients achieved pCR (p = 0.033). In contrast, missense mutations in PIK3CA and CNAs in CCND1, FGF19, FGF3, FGF4, SPOP, HNF1B and BRIP1 showed a trend of being less likely to mutate in pCR patients (p values between 0.05-0.1). Previous reports have suggested that pCR rates in HER2+ patients are associated with HR status. However, our data revealed comparable pathologic response of patients based on either HR status or neoadjuvant regimen. Conclusions: Our data revealed a distinct mutational profile between patients achieved pCR vs patients did not. Further studies with a larger cohort are required to confirm these findings.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer

2020 ◽  
Vol 16 (17) ◽  
pp. 1165-1177
Author(s):  
Yolanda Jerez ◽  
Blanca Herrero ◽  
Marta Arregui ◽  
Blanca Morón ◽  
Miguel Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Future Directions ◽  
Her2 Positive Breast Cancer ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

HER2-positive breast cancer accounts for 18–20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

scholarly journals Cost of Illness of HER2-Positive and Recurrent HER2-Positive Breast Cancer – A Danish Register-Based Study from 2005 to 2016

2021 ◽  
Author(s):  
Maria Spanggaard ◽  
Jens Olsen ◽  
Kenneth Forsström Jensen ◽  
Michael Andersson
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Healthcare Costs ◽  
Early Stage ◽  
Labour Productivity ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background: Information and knowledge about cost of illness and labour productivity in patients with HER2-positive early-stage and metastatic breast cancer treated with trastuzumab is limited. The aim of this study was to estimate the direct and indirect costs associated with treatment of HER2-positive breast cancer among patients with early-stage and metastatic breast cancer, treated with trastuzumab, in a 10-year period after diagnosis. Materials and Methods: This study included all Danish HER2-positive breast cancer patients (≥18 years) treated with trastuzumab between 2005 and 2016 identified in the Danish national registers. Among this population, patients experiencing metastatic breast cancer were identified. For the study populations, we estimated total healthcare costs and indirect costs for one year prior to the breast cancer diagnosis and up to 10 years after diagnosis compared with a group of matched controls free of breast cancer.Results: We identified 4,153 HER2-positive breast cancer patients, whereof 27% were identified with metastatic breast cancer. During the follow-up period of 10 years, we estimated excess healthcare costs of EUR 115,000 among the total study population compared to controls; EUR 211,000 among patients with recurrence; and EUR 89,000 among patients without recurrence. Healthcare costs were found to be highest in the first year after diagnosis and also peaked in the year after recurrence. Labour productivity was significantly lower among patients with recurrence 10 years after breast cancer diagnosis compared with controls.Conclusions: In this study, we estimated the direct and indirect cost associated with HER2-positive breast cancer to be significantly increased during the 10 years after diagnosis, specifically among patients experiencing recurrence of breast cancer.

scholarly journals ANTI-HER2 ANTIBODIES IN COMBINATION WITH CHEMOTHERAPY OR CHEMOTHERAPY-FREE REGIMENS TARGETING HER2-POSITIVE BREAST CANCER: A SYSTEMATIC REVIEW

2020 ◽  
Vol 20 (2) ◽  
pp. 285-306
Author(s):  
Siti Muhamad Nur Husna ◽  
Faezahtul Arbaeyah Hussain ◽  
Maya Mazuwin Yahya ◽  
Anne Dyhl-Polk ◽  
Kah Keng Wong
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Therapeutic Antibodies ◽  
Breast Cancer Patients ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.

Patterns of endocrine therapy in a national cohort of early stage HER2-positive breast cancer patients

2019 ◽  
Vol 28 (6) ◽  
pp. 812-820 ◽  
Author(s):  
Hanna E. Tervonen ◽  
Benjamin Daniels ◽  
Monica Tang ◽  
David B. Preen ◽  
Sallie-Anne Pearson
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
National Cohort ◽  
Positive Breast Cancer

scholarly journals Effects of Various Treatment Regimens on the Survival of HER2-positive Breast Cancer Patients with Brain Metastasis

The Physician ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. c12
Author(s):  
Shantal Edirappuli ◽  
Emma Bedowes
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Treatment Regimens ◽  
Her2 Positive Breast Cancer ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Overexpression of HER2 (human epidermal growth factor receptor 2) occurs in around 20% of breast cancers. This particular subtype is known to be very aggressive and had the worst prognosis prior to the introduction of targeted therapy. The development of anti-HER2 therapies such as trastuzumab and pertuzumab has shown to dramatically improve the prognosis of patients with HER2-positive breast cancer.

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