Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

Tomorrow's targeted therapies in breast cancer patients: What is the risk for increased radiation-induced cardiac toxicity?

Magné N, Chargari C, Macdermed D, Conforti R, Védrine L, Spano JP, Khayat D

Department of Medical Oncology, Hôpital Pitié Salpêtrière, Paris, France.

Ongoing clinical trials are now investigating the benefits of new targeted therapies, including ErbB and tyrosine kinase inhibitors (TKI) and antiangiogenics. Those may carry a potential risk for additional cardiac toxicity, particularly in association with radiotherapy. Although the risk of symptomatic cardiotoxicity is low, more subtle functional declines may increase mortality with longer follow-up and necessitate caution when assessing concurrent or sequential trastuzumab or lapatinib with radiotherapy. Potential additive toxicity encourages more conformal irradiation modalities minimizing cardiac dose, such as gating, intensity-modulated radiotherapy or Helical Tomotherapy. We recommend the collection of substantial information relevant to cardiac radiotoxicity in further clinical trials of targeted agents in breast cancer treatment, including doses delivered to cardiac structures, especially the coronary arteries. The incorporation of new biomarkers or modalities for assessment of cardiac function may also become necessary to detect cardiac toxicity at earliest stage.

Published 8 February 2010 in Crit Rev Oncol Hematol.
Full-text of this article is available online (may require subscription).

Articles on Herceptin published 8 February 2010:

In vitro evaluation of avidin antibody pretargeting using (211)At-labeled and biotinylated poly-L-lysine as effector molecule.   Cancer, 116: 1101-1110.

BACKGROUND:: Pretargeting is an approach for enhancing the therapeutic index of radioimmunotherapy by separating the administrations of tumor-targeting substance and radiolabel. In this study, a pretargeting model system of avidin-conjugated monoclonal antibody trastuzumab and biotinylated, (211)At-labeled poly-L-lysine was constructed and analyzed in vitro. METHODS:: Avidin activated by 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt ... [Abstract] [Full-text]

Improved efficacy of alpha-particle-targeted radiation therapy: dual targeting of human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72.   Cancer, 116: 1059-1066.

BACKGROUND:: Human epidermal growth factor receptor-2 (HER-2) and tumor-associated glycoprotein 72 (TAG-72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER-2, is effective in the treatment of disseminated intraperitoneal disease when labeled with (213)Bi or (212)Pb. (213)Bi-humanized CC49 monoclonal antibody (HuCC49DeltaCH2), which binds to TAG-72, inhibits the growth of subcutaneous xenografts. A next logical step to improve ... [Abstract] [Full-text]

HER2 targeting as a two-sided strategy for breast cancer diagnosis and treatment: Outlook and recent implications in nanomedical approaches.   Pharmacol Res.

At present, mammary carcinoma is the second most common type of malignant tumor in adult women after lung cancer, as more than one million women are diagnosed with breast cancer every year. Despite advances in diagnosis and treatment, which have resulted in a decrease in mortality in recent decades, breast cancer remains a major public health problem. One of the most significant unresolved clinical and scientific problems is the occurrence of resistance to clinical treatments and their toxicity ... [Abstract] [Full-text]

Articles on Herceptin published 5 February 2010:

Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up.   Breast Cancer Res Treat.

Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with TNB do not benefit from established targeted drugs with endocrine therapy or trastuzumab. The aim of the study was to analyze the prevalence of candidate biomarkers in tumors from patients with TNB. Tissue microarrays were prepared from primary tumors from premenopausal breast cancer patients (500/564) randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical (IHC) staining included ER, PR, ... [Abstract] [Full-text]

A Phase II Neoadjuvant Trial of Sequential Nanoparticle Albumin-Bound Paclitaxel Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide in Locally Advanced Breast Cancer.   Clin Breast Cancer, 10(1): 81-6.

Background: Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy. Patients and Methods: Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to ... [Abstract] [Full-text]

Pathologic Complete Response to Preoperative Sequential Doxorubicin/Cyclophosphamide and Single-Agent Taxane With or Without Trastuzumab in Stage II/III HER2-Positive Breast Cancer.   Clin Breast Cancer, 10(1): 40-5.

Background: Four major clinical trials have established that trastuzumab added to adjuvant systemic chemotherapy for women with HER2+ breast cancer significantly improves disease-free and overall survival compared with chemotherapy alone. We evaluated pathologic complete response (pCR) rate and cardiac safety of preoperative doxorubicin and cyclophosphamide followed by a taxane with or without trastuzumab. Patients and Methods: We reviewed pCR rate and change in left ventricular ejection ... [Abstract] [Full-text]

Understanding resistance to endocrine agents: molecular mechanisms and potential for intervention.   Clin Breast Cancer, 10(1): E6-E15.

Background: We developed a mouse model system that mimics hormone-dependent postmenopausal breast cancer. In this model, human estrogen receptor-positive (ER+) breast cancer cells (MCF-7) stably transfected with aromatase (MCF-7Ca) are grown as tumors in ovariectomized female nude mice. Using this model, we have established that aromatase inhibitors (AIs) such as letrozole and anastrozole that reduce estrogen production are more effective than the antiestrogen agent tamoxifen. This intratumoral ... [Abstract] [Full-text]

Trastuzumab and lapatinib beyond trastuzumab progression for metastatic breast cancer: strategies and pitfalls.   Expert Rev Anticancer Ther, 10(2): 179-84.

The discovery of HER2 gene amplification and protein overexpression in approximately 15-20% of breast cancers and access to the tailored humanized antibody, trastuzumab (Herceptin((R))), have heralded a new era in breast cancer therapy. Trastuzumab combined with chemotherapy has caused marked tumor responses and increased overall survival in patients with metastatic breast cancer, and has also increased survival in the adjuvant setting after radical surgery. However, due to many causes, ... [Abstract] [Full-text]

© 2004-2010 Herceptin Research Today. All Rights Reserved.