First Do No Harm: HER2-Positive Breast Cancer, Trastuzumab, and Cardiac Monitoring Guidelines

As one who developed severe cardiac effects secondary to my cancer treatment, I have been gratified to see the growing number of dedicated cardio-oncology programs across the country. As the June 2015 issue of the journal Evidence-Based Oncology powerfully highlighted, cancer survivors may be at risk for a number of cardiotoxicities due to their treatment that may emerge during active therapy or many years later as late effects. In addition, certain risk factors, preexisting cardiac conditions, and cardiac co-morbidities may limit therapeutic options for newly diagnosed or previously treated cancer patients, such as those with second cancers. With a growing understanding of the risk of cardiotoxicity associated with chemotherapeutic agents such as anthracyclines, chest radiation, and molecularly-targeted therapies, as well as the large number of patients with cardiac risk factors or co-morbidities, cardio-oncology has emerged as an important subspecialty, resulting in the establishment of cardio-oncology programs most often based at or in collaboration with comprehensive cancer centers.

In my role as an advocate, many of my efforts have concentrated on the need for greater knowledge among primary care providers (PCPs) and specialists other than oncologists regarding the very real risks for severe cardiotoxicities and other serious late effects in cancer survivors that may develop many years, often decades, after their treatment. (See “Radiation and Cardiotoxicity: A Cancer Survivor’s Story,” in Evidence-Based Oncology, June 2015 issue.) The fact is that, as reported by the American Society of Clinical Oncology’s “The State of Cancer Care in America: 2014,”¹ we are facing a severe upcoming shortage of oncologists in the United States. In addition, there is already an increasing number of cancer survivors who previously would have continued to see their oncologists yet who are now gradually being transitioned back to their PCPs. Yet a serious knowledge-gap concerning optimal cancer survivorship care remains among PCPs. In a striking study published in the Journal of General Internal Medicine in December 2011, a nationally representative sample of 1072 PCPs and 1130 medical oncologists were surveyed concerning their knowledge, attitudes, and practices for follow-up care of breast and colon cancer survivors. Entitled “Differences Between Primary Care Physicians’ and Oncologists’ Knowledge, Attitudes, and Practices Regarding the Care of Cancer Survivors,” the authors reported that “There are significant differences in PCPs' and oncologists' knowledge, attitudes, and practices with respect to care of cancer survivors. Improving cancer survivors' care may require more effective communication between these 2 groups to increase PCPs' confidence in their knowledge and must also address oncologists' attitudes regarding PCPs' ability to care for cancer survivors.” For example, concerning the respondents’ knowledge about breast cancer follow-up care components, the investigators found a large difference in reported confidence among PCPs and oncologists in caring for late physical effects of cancer, with 23% PCPs and 77% oncologists expressing high confidence in their knowledge.²

Yet the problem may run deeper. A recent study suggests that there may be gaps in knowledge of and/or insufficient adherence to certain clinical guidelines among some oncologists. ³ For patients with HER2+ breast cancer, incorporating the anti-HER2 targeted agent, trastuzumab, led to a paradigm shift in treatment, resulting in significant improvement in the prognosis of these aggressive breast cancers. Yet when this novel targeted agent was added to chemotherapy in the pivotal registration trial, an unexpectedly large percentage of patients developed congestive heart failure induced by trastuzumab, leading to a comprehensive retrospective cardiac evaluation of trial participants.^4,5 What followed included black box warnings, a growing body of medical literature, the development of cardiac monitoring guidelines—and now, for more than 15 years, the expectation of associated knowledge among the oncology community concerning the significant treatment-limiting trastuzumab-induced cardiotoxicities that have been reported to affect up to 34% of patients.⁶ Strikingly, however, new research suggests that most breast cancer patients who receive adjuvant trastuzumab do NOT receive adequate cardiac monitoring.

References

1. American Society of Clinical Oncology. The State of Cancer Care in America, 2014: a report by the American Society of Clinical Oncology. J Oncol Pract. 2014;10(2):119-142.

2. Potosky AL, Han PKJ, Rowland J, et al. Differences between primary care physicians’ and oncologists’ knowledge, attitudes and practices regarding the care of cancer survivors. J Gen Intern Med. 2011;26(12):1403-1410.

3. Chavez-MacGregor M, Niu J, Zhang N, Elting LS, et al. Cardiac monitoring during adjuvant trastuzumab-based chemotherapy among older patients with breast cancer. J Clin Oncol. 2014;58:9465.

4. Saad A, Abraham J. Trastuzumab and cardiac toxicity: monitoring in the adjuvant setting. Commun Oncol. 2007;4:739-744.

5. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001:344(11):783-792.

6. Onitilo AA, Engel JM, Stankowski RV. Cardiovascular toxicity associated with adjuvant trastuzumab therapy. Ther Adv Drug Saf. 2014;5(4):154-166.

For part 2 of Ms Madden's article, “First Do No Harm,” please tune-in after a week.