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Is trastuzumab plus endocrine therapy sufficient for patients who are triple positive but node negative, or do they also require chemotherapy?
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There are no data to support the elimination chemotherapy.
There are no data about the use of either trastuzumab alone for adjuvant treatment of HER-2–positive breast cancers regardless of size, or trastuzumab with just hormone therapy. There also are no direct data on how much added benefit you get by adding trastuzumab to chemotherapy for tumors smaller than 1 cm. The group about which we have the least data are the smallest HER-2–positive breast cancers, the T1a cancers, because they are diagnosed very infrequently. The current NCCN guidelines recommend appropriately only hormone therapy (if ER-positive) for these smallest cancers.
Based on the BCIRG 006 and HERA trials, chemotherapy remains part of the armamentarium for treating HER-2–positive breast cancers larger than 1 cm. The question regarding optimal treatment for node negative tumors smaller than 1 cm is not going to be answerable in a randomized, clinical trial — there just are not enough of these patients out there. If you give such patients trastuzumab, or chemotherapy, or chemotherapy plus trastuzumab, or trastuzumab plus hormone therapy, the event rate is going to be very low and such a study would require huge numbers to find small differences.
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Although this will not be the subject of a randomized trial, information from phase-2 studies may shed some light. For example, the group at Dana-Farber, in collaboration with other cancer centers, is doing a phase-2 nonrandomized study combining paclitaxel with trastuzumab for HER-2–positive cancers smaller than 1 cm.
A lot of what we can say about treating T1b cancers is extrapolated from the relative risk reductions seen in the adjuvant trials with larger node-negative tumors and the fact population based studies show that HER-2–positive cancers less that 1 cm (mostly T1b) appear to carry a recurrence risk of at least 10% if untreated. The current guideline for T1b cancers, namely, to consider treatment with chemotherapy or chemotherapy plus trastuzumab is supported by the indirect evidence that is available. We are going to see more data over time that directly address these issues. Right now, I think that chemotherapy for these cancers is probably worth it provided there is an appropriate risk/benefit discussion with the patient.
Edward H. Romond, MD, is a Professor of Medicine at the University of Kentucky Markey Cancer Center Comprehensive Breast Care Center in Lexington, Ky.
Although an important question, the data are immature.
For patients with early stage breast cancer that is ER-positive and progesterone receptor-positive, the presence of HER-2-neu overexpression is associated with an increased risk for recurrence when treated with endocrine therapy alone, even in the setting of smaller lymph node-negative cancers. Although the combination of endocrine therapy and trastuzumab has been used in the treatment of metastatic disease, trastuzumab without chemotherapy remains unproven in the curative intent situation. Although this option may be considered in individuals who either decline or are not appropriate candidates for chemotherapy, inclusion of chemotherapy is indicated for most patients with HR-positive, HER-2–neu–positive, lymph node-negative early stage breast cancer.
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If we are looking at all node-negative, HR-positive, HER-2–positive tumors vs. the very small tumors, I think we are all very comfortable thinking that patients with HER-2–positive and HR-positive tumors of 1 cm or larger should have chemotherapy as well as trastuzumab.
The difficulty comes with these very small cancers. I do not think anyone knows the cutoff where we would not recommend chemotherapy, but the recurrence risk with these tumors may not be sufficient to be worth the toxicity of chemotherapy.
If a physician is going to eliminate chemotherapy and just go with trastuzumab plus endocrine therapy, you need to explain to the patient that we do not have data to support that. It is a very important research question — there are studies in development that hope to address whether targeted anti-HER-2 therapy with endocrine therapy will be a successful approach for these small tumors — but none of those studies has been completed and we do not have definitive results.
Halle Moore, MD, is a Staff Physician in Solid Tumor Oncology with Cleveland Clinic’s Taussig Cancer Institute.