A number of treatment options are targeted at HER2-positive breast cancer, including carboplatin, anthacycline, and pertuzumab. Although this multitude of options has enhanced breast cancer outcomes for both early-stage and advanced-stage patients, overtreatment is a concern. A means to determine individualized, optimal risk/benefit ratios of treatments for patients is necessary in order to fully utilize the treatments available for breast cancer.
According to “HER2-Positive Breast Cancer, Intrinsic Subtypes, and Tailoring Therapy,” published in JNCI Journal of the National Cancer Insitute, pathological stage is commonly used to guide clinicians’ choice of treatment for their patients. For example, pertuzumab, a HER2 dimerization inhibitor, is recommended for patients with pathological stage III disease, as patients with stage I/IIA, HER2-positive breast cancers are effectively treated with 12 weeks of weekly paclitaxel and a year of trastuzumab. This approach is preferred, as paclitaxel with trastuzumab is simpler and more cost effective.
Another approach for tailoring treatments to breast cancer subtypes is gene expression profiling. Amplification of HER2 can be prognositic for intrinsic subtype. Luminal A breast cancers show the lowest incidence of HER2 amplification (7.3%), followed by basal-like (14.4%), luminal B (20.0%), and HER2-enriched (64.6%). Interestingly, HER2 status does not affect the outcome of individual treatments for these intrinsic subtypes when non-HER2-directed treatments, such as pre-trastuzumab, are used.
As an example of applying genetic results, high levels of HER2 expression often lead to rapidly progressing breast masses, suggesting efficacy for neoadjuvant treatments. However, sequencing and gene copy analysis can sometimes show different molecular characteristics, leading studies to draw conflicting conclusions.
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The largest concern with drawing conclusions from studies as facts that can be applied to all patients is the limited size of some studies. An overrepresented tumor type, such as luminal A HER2-positive, could decrease event rates in HER-directed therapy studies and dilute the power of analysis.
The authors of this study believe the best means forward for the future is to validate an assay for intrinsic subtype and apply it to tissue biopsies in order to conduct retrospective analyses of HER2-targeted clinical trials. These data would provide clinicians with more concrete facts on which to base their treatment recommendations.