Subtyping improves selection for breast cancer patients facing chemotherapy

Adjuvant chemotherapy may not be the best option for patients with certain subtypes of breast cancer who show no clear benefit, according to an extensive retrospective of four clinical trials published June 12 in Breast Cancer Research and Treatment.

Stefan Gluck, MD, PhD, professor of medicine at Sylvester Comprehensive Cancer Center and Leonard M. Miller School of Medicine at the University of Miami, and colleagues conducted a meta-analysis of data from 437 early-stage breast cancer patients enrolled in four independent neoadjuvant chemotherapy clinical trials to correlate pathologic complete response rate as a result of treatment and long-term, distant metastases-free survival (DMFS). The model for subtyping utilized gene-expression array analysis in two formats, BluePrint and MammaPrint molecular subtyping, which was then compared to immunohistochemistry and fluorescence in situ hybridization (IHC/FISH) to gather information about estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 (HER2).

“Molecular subtyping can improve the stratification of patients in the neoadjuvant setting: Luminal A-type (MammaPrint Low Risk) patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy,” wrote Gluck et al. “We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2-type and Basal-type. BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC/FISH.”

Outcomes of BluePrint and MammaPrint analysis were assessed from 44K Agilent arrays, the I-SPY 1 data portal, or Affymetrix U133A arrays. Pathologic complete response varied widely among the BluePrint subtypes, including 47 percent for HER2-type, 37 percent in Basal-type, 10 percent in Luminal B-type and 6 percent in Luminal A-type. Five-year DMFS rate was found to be 93 percent in the 90 patients with Luminal A-type breast cancer. This group included eight triple-negative patients by IHC/FISH and seven HER2-positive patients. Their outcomes showed excellent survival.

“The [progression complete response] rate provided no prognostic information, suggesting these patients may not benefit from chemotherapy,” the authors wrote.

These data are in line with previous studies that have revealed a disparity in the benefit of neoadjuvant chemotherapy, such as with trastuzumab, for various subtypes of breast cancers.

“Our results also confirm the importance of classifying breast cancer into molecular subtypes to select the appropriate patients who will benefit from neoadjuvant chemotherapy,” wrote the researchers. “However, we should point out that our analysis was not prospective and was performed on data from trials involving different institutions, chemotherapy regimens, and definitions of [progression complete response.]”