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HER2-Positive Breast Cancer

HER2-Positive Breast Cancer

This review discusses the treatment of primary, nonmetastatic HER2-positive breast cancer in the adjuvant and neoadjuvant settings—settings in which tremendous progress has been made.

Therapies targeting HER2 have revolutionized the treatment of breast cancer. Trastuzumab is the foundation of treatment for women with HER2-positive breast cancer. The challenge ahead is to develop predictors that can identify patients for whom trastuzumab alone will be sufficient.

It will be critically important to await the longer-term DFS and OS results from the neoadjuvant studies, as well as the adjuvant studies evaluating dual HER2 blockade, prior to these approaches truly becoming the standard of care.

A phase I study of intermittent oral lapatinib in patients with HER2-amplified breast cancer escalated up to 7,000 mg per day (shown to be effective in mouse models), found that plasma concentrations of the drug did not increase proportionately with the oral dose, impeding clinical translation of this method.

Older age and comorbidities were associated with a higher risk of failing to complete trastuzumab therapy in a new study of older women with early-stage breast cancer, where nearly 20% failed to complete the treatment.

This article discusses the development of pertuzumab to date, with a particular focus on the accelerated approval decision. We highlight the need to identify reliable biomarkers of sensitivity and resistance to HER2-targeted therapy, which would make possible the individualization of treatment for patients with HER2-positive breast cancer.

Contrary to some expectations, getting accelerated approval for neoadjuvant therapy does not look easy, and the pertuzumab story may be the exception that proves the rule.


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