Cardiotoxicity in Primary Breast Cancer: Expert Responses to Frequently Asked Questions

Ms. Major Campos is a clinical nurse specialist in medical oncology at Memorial Sloan-Kettering Cancer Center in New York City. She received her master's degree in nursing from Columbia University in New York City. She works in a collaborative practice model managing patients receiving medical care for breast cancer. Her practice is focused on symptom management, patient education, triage, and protocol coordination. Ms. Major Campos is viewed as a clinical expert and lectures extensively on breast cancer patient care.

Maureen Major Campos, RN, MS, reported a financial interest/relationship or affiliation in the form of: Speakers’ Bureau, Genentech BioOncology, Abraxis Oncology, and Amgen, Inc.

Case Discussions Based on Oncology Nurse Submissions

Improvements in adjuvant therapy will continue to prolong overall survival in women diagnosed with early stage breast cancer. Nurses have an opportunity to educate this patient population regarding clinical trial data and therefore influence adherence to therapy. A nursing assessment at each treatment infusion can also influence appropriate management of a patient with declining cardiac function. A significant emphasis has been placed on survivorship in this patient population as science continues to advance its understanding of the patterns of breast cancer growth. Quality of life studies are needed to further understand the impact of adjuvant treatment on the healthy population of patients who undergo adjuvant treatment.

Breast Cancer Survivorship Pyschological Support Update

In recent years, cancer survivorship issues have received greater attention and research interest as the number of cancer survivors increases in the United States, and the cancer advocacy movement gains in strength. Cancer survivorship is defined as a continuum from the time of diagnosis to the end of life. It has been conceptualized as a progression through three phases or “seasons” of survival incorporating: (1) surviving the treatment and its side effects, (2) beginning to return to normal life while being monitored for recurrence, and (3) long-term adjustment, when the cancer experience is viewed as an episode in a full life. In 2004, the most recent year with complete Surveillance, Epidemiology, and End Results (SEER) data, there were 10.1 million cancer survivors; of these, more than 2.4 million were breast cancer survivors. Family members, friends, and caregivers of the woman diagnosed with breast cancer are also considered to be cancer survivors.

Psychosocial distress, at varying levels of severity, accompanies the cancer experience. There are calls to consider distress the sixth vital sign; it would then be routinely monitored along with pulse, blood pressure, respiration, temperature, and pain. Periods of highest distress for the woman with breast cancer are associated with transition points in treatment. Completion of treatment may be a cause of increased anxiety rather than joy. There are many potential barriers to meeting the psychosocial needs of women with breast cancer after active treatments ends. The Institute of Medicine of the National Academies has released several reports during recent years describing strategies to acknowledge and meet these needs, declaring that provision of psychosocial services should be a standard of care for survivors of cancer. Oncology nurses play a key role in assessing the patient, family members, and caregivers for signs of distress. In so doing, an atmosphere of compassion and trust is created such that the breast cancer survivor feels free to share psychosocial concerns and have them addressed by appropriate specialists if necessary.

Dr. Ewer is a professor of medicine at the University of Texas M. D. Anderson Cancer Center, Houston. He received his doctor of medicine from the University of Basel Medical Faculty, Switzerland, and received his doctor of jurisprudence from the University of Houston Law Center. His special interests include cardiotoxicity of anticancer treatments, medical ethics, and patients’ rights. He has written more than 200 publications and lectures frequently throughout the United States, Europe, and Asia.

Michael Ewer, MD, reported a financial interest/relationship of affiliation in the form of: Consultant, Roche Laboratories, Inc., sanofi-aventis U.S., and Genentech BioOncology; Speakers' Bureaus, Roche Laboratories, Inc., sanofi-aventis U.S., and Genentech BioOncology..

Anthracyclines and HER2 Inhibitors: Benefits vs. Risks

Myocardial dysfunction is the most commonly discussed manifestation of cardiotoxicity associated with cancer therapy, however, other equally troubling effects include ischemia, dysrhythmia, and pericardial toxicities. It is now recognized that therapeutic agents, particularly the anthracyclines, may cause myocyte damage and death. This form of damage, referred to as Type I chemotherapy-related cardiac dysfunction (CRCD), has characteristic ultrastructural properties. Despite substantial loss of myocytes, the heart, as an organ with considerable reserves, often compensates and does not exhibit clinical evidence of damage unless additional factors or toxicities cause sequential cardiac stress, further cell damage, and ultimately, clinically recognizable dysfunction.

Other agents, most notably trastuzumab, cause a temporary loss of contractile function, but with a much lower propensity for progressing to cell death. In isolated state, cardiac dysfunction resulting from these agents, now referred to as Type II CRCD, typically recovers to near baseline levels. However, as many patients are treated with a Type I CRCD-causing agent followed by a Type II agent, the first may result in a subclinical injury that surfaces as a result of the additive dysfunction caused by a subsequent insult. Because both Type I and Type II CRCD-causing agents lead to decreased cardiac contractility, their relative contributions to cardiac dysfunction cannot be determined using available clinical tools.We are only now beginning to understand these interactions and develop strategies for the proper screening, monitoring, surveillance, and treatment of cardiac dysfunction associated with cancer therapy.

Update on Clinical Trials of Antiangiogenesis Agents in Breast Cancer/Metastatic Breast Cancer Treatment Update

Metastatic breast cancer (MBC) remains a largely incurable disease. However, survival rates continue to increase as advances in the understanding of the biology of tumorigenesis are made. Angiogenesis plays a major role in tumor formation and therefore, agents targeting this process, including the monoclonal antibody bevacizumab, are particularly successful at treating tumors. In addition, the introduction of the monoclonal antibody trastuzumab has dramatically improved outcomes for women with human epidermal growth factor receptor 2 (HER2)-positive MBC and reaffirmed the value of targeting specific cellular proteins as a means of controlling disease. This has led to the development of a plethora of new agents for the treatment of HER2-positive breast cancer in the metastatic setting, though optimal chemotherapy regimens are still under investigation.

Dr. Giordano is an assistant professor in the Department of Breast Medical Oncology at the University of Texas M. D. Anderson Cancer Center, Houston. She also serves as a vice-chairperson on M. D. Anderson’s Institutional Review Board. She received her doctor of medicine from the Johns Hopkins School of Medicine, Baltimore, Maryland, and completed her fellowship at the University of Texas M. D. Anderson Cancer Center. Dr. Giordano’s research interests include breast cancer in the elderly, breast cancer outcomes, and male breast cancer. She is an active member of the American Society of Clinical Oncology and American Association for Cancer Research.

Sharon Giordano, MD, MPH, reported a financial interest/relationship or affiliation in the form of: Speakers' Bureau, Roche Laboratories, Inc.

Anthracyclines and HER2 Inhibitors: Benefits vs. Risks

Anthracyclines and HER2 inhibitors (eg, trastuzumab) are among the most important agents in the treatment of breast cancer. Anthracycline-based chemotherapy improves survival of patients with early stage breast cancer; the new nonanthracycline regimen of docetaxel and cyclophosphamide has also proved effective. In addition, trastuzumab, a humanized monoclonal antibody directed against HER2, improves overall survival of patients with HER2-positive early stage breast cancer as well as metastatic breast cancer; it is associated with a 40% to 50% reduction in risk of death from breast cancer. Despite their efficacy, anthracyclines and HER2 inhibitors also carry a risk of cardiac dysfunction. Patients treated with anthracyclines are at an increased risk of developing congestive heart failure, particularly with increasing cumulative dose. In addition, older patients, those who have preexisting cardiac disease, or patients treated concurrently with anthracyclines and HER2 inhibitors, may be at an even greater risk. It is therefore crucial that patients are monitored closely for signs of cardiac impairment in order to minimize the risks without compromising the level of benefit derived.