A new evidence-based practice guideline from the American Society of Clinical Oncology on treating women with advanced breast cancer that is negative for human epidermal growth factor receptor 2 emphasizes that "optimal" chemotherapy regimens may vary considerably between patients.
When choosing treatment for an individual with HER2-negative breast cancer, consider not only the potential efficacy of a therapy but also the potential toxicity, the patient’s performance status and comorbid conditions, history of prior therapy, whether the cancer is indolent or immediately life threatening, and the patient’s preferences and schedule, the guideline states.
Dr. Ann Partridge
That said, the guideline on "Chemotherapy and Targeted Therapy for Women with Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer" offers some specific recommendations (J. Clin. Oncol. 2014 Sept. 2 [doi:10.1200/JCO.2014.56.7479]).
First-line treatment should be endocrine therapy if the patient has metastatic HER2-negative breast cancer that’s also estrogen receptor positive, unless the disease is immediately life threatening or there is concern about potential resistance to hormone therapy.
Treating with single chemotherapy drugs (in sequential trials, if needed) is preferable to combination chemotherapy for HER2-negative breast cancer in order to limit side effects and help preserve the patient’s quality of life, the guideline states. Although a longer duration of chemotherapy can improve survival, this must be balanced against the treatment’s toxicity.
Use of targeted therapy with bevacizumab, a monoclonal antibody, remains controversial and should only be considered with single-agent chemotherapy for patients with immediately life-threatening disease or severe symptoms, the guideline suggests. Bevacizumab is not approved in the United States to treat breast cancer.
Other targeted therapies have not been shown to improve outcomes in women with advanced HER2-negative breast cancer and should not be used with or instead of chemotherapy in these patients.
Offer palliative care early and throughout the continuum of care, the guideline recommends.
"Although no clear chemotherapy winner emerged, the guideline will help doctors and patients choose the best therapy based on what treatment would be most tolerable and convenient for the patient," Dr. Ann H. Partridge said in an American Society of Clinical Oncology statement. Dr. Partridge cochaired the expert panel that developed the guideline and is director of the Adult Survivorship Program and the Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute, Boston.
Some of the many treatments available for HER2-negative breast cancer are "unnecessarily toxic," expert panel cochair Dr. Ian E. Smith said in the ASCO statement. "Breast cancer can often be controlled with less intensive approaches that offer a better quality of life," said Dr. Smith, a professor of cancer medicine at Royal Marsden Hospital, London.
ASCO’s consensus-driven expert panel reviewed randomized studies in the medical literature from 1993 through May 2013 and used the 2009 systematic review by the National Collaborating Centre for Cancer in England as a starting point for what’s known. The panel considered 79 studies, including 20 systematic reviews or meta-analyses, 30 trials of first-line treatments, and 29 trials of second-line or subsequent treatments.
A majority of patients with advanced breast cancer have HER2-negative disease, for which development of targeted therapies is in the early stages. The current speed of research progress in cancer genomics and potential targets of drug therapy is likely to produce new targeted therapies soon to enhance or replace chemotherapy, the guideline authors predicted.
Even then, collaboration between physician and patient to find the optimal approach will remain key. "Given the heterogeneity of breast cancer, even when restricted to HER2-negative disease, it is also possible that ‘one size will never fit all’ and that there is no best treatment for most patients," they wrote.
Dr. Partridge and Dr. Smith reported having no financial disclosures. Disclosures for several of their coauthors who reported having associations with pharmaceutical companies are available with the article online.
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