Trastuzumab for breast cancer by Ray Sahelian, M.D.
April 12 2016

Trastuzumab (Herceptin) is a monoclonal antibody recommended for women with human epidermal growth receptor 2 (HER-2)-positive breast cancer, either alone or as adjunctive treatment with chemotherapy.

Trastuzumab side effects
Treatment with trastuzumab for more than 1 year appears to reduce cardiac function and increase the risk of congestive heart failure. This cardiotoxicity appears to be reversible. Cardiotoxicity is even more common when trastuzumab is combined with anthracyclines. Dr. Francisco J. Esteva and colleagues assessed cardiotoxicity among 173 women with metastatic breast cancer positive for HER-2 and treated at the University of Texas M.D. Anderson Cancer Center in Houston for at least 1 year. A total of 49 (28%) patients experienced a cardiac event, defined as an asymptomatic decrease in left ventricular ejection fraction below 50%, a decrease of 20% in LVEF compared with baseline, or evidence of congestive heart failure. Among the 15 symptomatic patients, 14 discontinued trastuzumab, and 11 recovered after treatment with a beta-blocker or ACE inhibitor. One patient died after developing congestive heart failure. To minimize adverse effects, Dr. Francisco J. Esteva suggest that cardiac function be evaluated before starting trastuzumab, especially if the patient has already undergone treatment with an anthracycline. J Clin Oncol 2006.

J Clin Oncol. 2013. Trastuzumab-related cardiotoxicity among older patients with breast cancer. The use of trastuzumab in the adjuvant setting improves outcomes but is associated with cardiotoxicity manifested as congestive heart failure (CHF). The rates and risk factors associated with trastuzumab-related CHF among older patients are unknown.

Trastuzumab for breast cancer
Treatment with trastuzumab ( Herceptin ) for 1 year after adjuvant chemotherapy can increase overall survival for women with HER2-positive breast cancer. Treatment with trastuzumab, a monoclonal antibody to HER2, has been previously shown to increase disease-free survival in chemotherapy-treated women with HER2-positive disease. The focus of the present analysis, which used data from the Herceptin Adjuvant (HERA) trial, was to determine if this therapy also improved overall survival. Dr. Ian Smith, from the Royal Marsden Hospital in London, and colleagues assessed overall survival in 1703 HERA participants who were randomized to receive trastuzumab for 1 year after chemotherapy and in 1698 who were randomized to receive only chemotherapy. The women had HER2-positive breast cancer that was either node-positive or high-risk node negative. The median follow-up period was 2 years.
Early discontinuation of trastuzumab was noted in 172 patients. Fifty-nine women in the trastuzumab group and 90 in the control group died. This translates into a 34% reduced risk of death with trastuzumab use. Disease-free survival events were significantly less common in the trastuzumab group compared with controls: 218 vs. 321. Thus, trastuzumab cut the risk of such events by 36%. A longer evaluation is needed to determine what kind of trastuzumab cardiac side effects will come about after 2 years of treatment. Lancet 2007;369:3-5,29-36.

Resistance to treatment
Clin Med Insights Oncol. 2016. Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It. The introduction of trastuzumab therapy markedly improved the poor prognosis associated with HER2-amplified breast cancers. Despite this, the presence of primary and acquired resistance to trastuzumab treatment remains a significant common challenge. The identification of resistance mechanisms and the incorporation of new drugs that achieve a better blockade of HER family receptors signaling have resulted in improved outcomes. The phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin pathway, cross-talk with estrogen receptors, immune response, cell cycle control mechanisms, and other tyrosine kinase receptors such as insulin-like growth factor I receptor are potential pathways involved in trastuzumab resistance.