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Patients whose disease progresses or relapses on trastuzumab now have 3 new
therapeutic options: lapatinib, pertuzumab, and T-DM1. Each of these agents has a unique
mechanism of targeting HER-2 signaling and cross-talk among HER family members. When
considering treatment for patients past the first-line setting, the goals of therapy should be
to improve survival and minimize treatment-related toxicity. Only T-DM1 has demonstrated
survival benefits over other traditional choices, such as lapatinib and capecitabine, and
should therefore represent a standard of care for second-line patients. Dual HER2 blockade
with lapatinib and trastuzumab also led to a survival advantage over lapatinib alone in
more heavily pretreated patients than those enrolled in EMILIA. This combination of HER2-
targeting agents also offers a low toxicity profile. Finally, once T-DM1 and lapatinib strategies
have been exhausted, continuation of trastuzumab in combination with chemotherapy has
proven activity. The increasing number of options in the second-line setting and beyond is
good news for patients faced with trastuzumab-refractory metastatic breast cancer

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