Chemotherapy for HER2-negative Metastatic Breast Cancer

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The future of chemotherapy-based options for patients with HER2-negative MBC is evolving, with emerging agents and combinations being studied in ongoing clinical trials.
The future of chemotherapy-based options for patients with HER2-negative MBC is evolving, with emerging agents and combinations being studied in ongoing clinical trials.

Though nearly all patients with metastatic breast cancer (MBC) — particularly those with HER2-negative disease — will at some point receive chemotherapy, some experts suggest that despite the availability of international guidelines, there is no established standard treatment algorithm, an absence that may lead to arbitrary decisions.1

Sara M. Tolaney, MD, MPH, of the Dana-Farber Cancer Institute in Boston, Massachusetts, told Cancer Therapy Advisor, however, that most US physicians follow the National Comprehensive Cancer Network (NCCN) guideline.2 Though there are multiple chemotherapy options for metastatic disease, specific patient- or treatment-related characteristics can aid in treatment selection.

For HER2-negative disease, the treatment course may differ depending on hormone dependence and other factors.

Triple-negative Disease

“From a standard of care perspective for triple-negative disease, there really is only chemotherapy,” Dr Tolaney said. Some factors that are considered when selecting the specific agent include what they received as adjuvant therapy and their disease-free interval. Dr Tolaney added that she is less inclined to use the same type of chemotherapy if the disease-free interval was less than a year, but it may be an option if the patient relapses after a year.

The foundational algorithm for the treatment of HER2-negative MBC is outlined by the NCCN guideline.2 According to Dr Tolaney, “usually the first-line standard is a taxane, the second-line is typically capecitabine, and the third-line is eribulin. The permutation depends on what prior therapies the patient had and whether they have a BRCA mutation.”

A common adjuvant treatment, for example, is a single-agent anthracycline. As a result, Dr Tolaney said that “we don't use a lot of anthracyclines in the metastatic setting, but sometimes I will use liposomal doxorubicin in a patient who didn't have an adjuvant anthracycline.”

Another important factor is BRCA status. “I will often consider using first-line platinum, such as cisplatin or carboplatin, instead of a single-agent taxane because there are data that suggest platinum is more effective than taxanes in the first line for the BRCA-mutant population,” Dr Tolaney said.  

She noted that the “use of platinum therapy in triple-negative disease is still somewhat controversial about when to use it and how to use it, and that gets more into the art of therapy rather than the exact science.” Platinum-based chemotherapy improved overall survival and progression-free survival among patients with TNBC [triple-negative breast cancer], and a greater objective response rate among patients with BRCA-mutated TNBC, but not in an unselected TNBC population.1

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