1. Breast tumors with stem cell mutations in the PI3K/Akt signaling pathway had significantly higher rates of axillary lymph node metastases.
2. Among women with breast tumors with stem cell mutations, 30% experienced disease progression after treatment and 20% died from the disease, compared to 0% in women with non-mutation breast cancers.
Evidence Rating Level: 2 (Good)
Study Rundown: This study found that breast tumors with stem cells carrying mutations in the PI3K/Akt signaling pathway were significantly more likely to have axillary lymph node metastases than tumors without such mutations. Results suggest that stem cell mutations may serve as a novel prognostic indicator. However, generalizability of findings is limited by a small sample size (n=30) and relatively short follow-up (mean= 2years). Future studies might evaluate stem cell mutations and prognosis in a larger cohort with longer-term follow-up. Others could assess therapeutic benefit of PI3K/Akt inhibitors currently in trials by stem cell mutation status.
Relevant Reading: Uptodate: Measurement of prognostic factors in breast cancer
Study Author, Dr. SuEllen Pommier, PhD, talks to 2 Minute Medicine: Oregon Health & Science University, Research Associate Professor, Division of Surgical Oncology
“Breast cancer stem/progenitor cells make up only a small portion of the total number of cells within a breast cancer and can be missed in whole tumor testing. They, however, as this study demonstrated, provide crucial prognostic and treatment information and thus should be independently tested along with whole tumor analyses. Through further investigation of breast cancers and their stem/progenitor cells our intention is to provide an improved prognostic tool that will guide more effective breast cancer treatment strategies”
In-Depth [retrospective cohort study]: This study compared breast cancer stem cells (BCSCs) from breast tumors from 30 women with and without mutations in the PI3K/Akt signaling pathway, specifically in the AKT1, HRAS, and PIK3CA genes. Race/ethnicity, age at diagnosis, tumor hormone receptor status, HER2/Neu status, tumor histologic grade, pathologic tumor stage, and condition at last follow-up were retrospectively determined. Of the 30 samples obtained, 10 (33%) contained BCSCs with mutations in AKT1, HRAS, or PIK3CA.
The presence of a BCSC mutation was associated with a significantly higher likelihood of having axillary lymph node metastases (including micrometastases) (9/10 vs 4/20, p=.001). At the time of analysis, 30% of the mutation cohort had disease progression after treatment and 20% died from the disease, compared to 0% of the non-mutation group, although the mutation cohort had a significantly longer follow-up period than the non-mutation group (29 months vs 19 months, p=.001).
By Maren Shapiro and Leah Hawkins, MD, MPH
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