Molecular subtyping identifies breast cancer patients not benefiting from neoadjuvant chemo

A group of patients with early-stage, invasive breast cancer who do not benefit from neoadjuvant chemotherapy have been identified by molecular subtyping. The group could not be identified by the methods of traditional clinical pathology.

This study compared the findings of molecular subtyping to those of traditional clinical pathology to determine breast cancer type. Breast cancer types include luminal A, luminal B, HER2, and basal. The luminal A (low risk) and luminal B (high risk) subtypes cannot be differentiated by standard pathology.

 “Molecular subtyping shows the potential of precision medicine in early breast cancer therapy,” said study leader Stefan Glück, MD, PhD, of the University of Miami's Comprehensive Cancer Center in Florida. “In this study, the advantages of molecular subtyping allowed us to identify both patients who could avoid chemotherapy prior to surgery, and those for whom chemotherapy provides a benefit.”

Data from four clinical trials with a total of 437 patients was analyzed retrospectively. Among these patients, 90 women (21%) had little if any benefit from chemotherapy and had good outcomes 5 years after surgery. This group represented the luminal A subtype, which was identified by BluePrint and MammaPrint assays. The study was published in Breast Cancer Research and Treatment (2013; doi:10.1007/s10549-013-2572-4).

The patients with luminal A-type breast cancer had low rates of pathologic complete response (pCR; 6%), showing little if any benefit from chemotherapy, but a good prognosis. At 5 years, their rate of distant metastases-free survival was excellent at 93%. The worst prognosis and worst 5-year rate of distant metastases-free survival (54%) was found for patients with basal-type breast cancer with residual disease.

The patients analyzed in this study were enrolled in one of four independent neoadjuvant chemotherapy trials: 144 patients from the I-SPY 1 trial, 131 patients and 99 patients from two biomarker discovery trials at the University of Texas M.D. Anderson Cancer Center, and 63 patients from the City of Hope National Medical Center.

Among trastuzumab-treated patients, a subgroup analysis found that molecular subtyping is potentially more accurate in predicting response to trastuzumab than standard pathology with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Among patients whose breast cancer was classified as HER2 type by molecular subtyping, 62% had a pCR, while only 47% had a pCR based on HER2 classification by IHC/FISH. The rate of pCR can serve as a surrogate for long-term outcome, though pCR provides little prognostic value for luminal A-type disease.

The authors suggested that this analysis of molecular subtyping “has treatment implications for a substantial portion of patients who are currently selected for neoadjuvant chemotherapy treatment based on IHC/FISH assessment.” They further add that their research confirms the importance of classifying breast cancer patients into molecular subtypes so patients can be appropriately selected to receive neoadjuvant chemotherapy.
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