Nodal Metastases More Likely if Tumors Have Breast Cancer Stem and Progenitor Cells With PI3K/Akt Signaling Defects 


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Patients with breast tumors in which breast cancer stem and progenitor cells have a genetic abnormality of the PI3K/Akt signaling pathway are more likely to have lymph node metastases, according to a study in JAMA Surgery. “These oncogenic defects may be missed by gross molecular testing of the tumor and are markers of more aggressive breast cancer,” the researchers reported. “Molecular profiling of [breast cancer stem and progenitor cells] may identify patients who would likely benefit from PI3K/Akt inhibitors, which are being tested in clinical trials.”

The study involved 30 women with invasive ductal carcinoma of the breast exceeding 1.0 cm. “Solid-tissue breast specimens were collected at the time of mastectomy or lumpectomy before any adjuvant treatment,” the investigators explained. “Following tissue analysis, medical records were reviewed, and additional data were compiled retrospectively for each patient.”

Positive lymph nodes were identified in six patients and micrometastatic deposits, defined as < 0.2-cm metastatic focus of tumor, in another six. Patients with macroscopic lymph node metastases had axillary lymph node dissection, but patients with only micrometastatic disease did not. Of the 30 tumors, 10 had breast cancer stem and progenitor cells with AKT1, HRAS, or PIK3CA mutations. 

Significant Correlation

The investigators found a statistically significant correlation between the presence of breast cancer stem and progenitor cell mutations and axillary lymph node metastases (P = .02). “This significance was more pronounced when micrometastatic disease was included (P = .001),” the researchers stated.

Of the 10 patients with breast cancer stem and progenitor cell mutations, 3 had disease progression following chemotherapy, hormone therapy, and a trastuzumab (Herceptin) regimen. Two of those patients died of disease, and one had brain metastases. None of the patients with breast cancer stem and progenitor cells without mutations had evidence of disease. The mean follow-up was 29 months for patients with breast cancer stem and progenitor cell mutations and 19 months for those without such mutations, and the authors noted the difference was statistically significant (P = .001).

“While axillary lymph node metastases are known to correlate with tumor size, [breast cancer stem cell and progenitor cell] mutation in this study was an independent predictor of lymph node metastasis,” the authors wrote. “Because 4 of 20 patients (20%) without [such] mutations had axillary lymph node metastases, a PI3K/Akt mutation in [breast cancer stem and progenitor cells] may not be a requirement for axillary lymph node metastases. However, a significant correlation was found between the two factors, with 9 of 10 patients (90%) with [breast cancer stem and progenitor cell] mutations having nodal metastases. Five of 10 patients (50%) with [breast cancer stem and progenitor cell] mutations had axillary lymph node macrometastatic disease, and an additional 4 of 10 patients (40%) had micrometastatic disease.”

The authors concluded that the results of the study “support concomitant evaluation of [breast cancer stem and progenitor cells] along with assessment of the breast cancer overall.” ■

Donovan CA, et al: JAMA Surgery. July 24, 2013 (early release online).



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