A new marker that identifies a more aggressive form of breast cancer has been reported. Tumors in which breast cancer stem and progenitor cells have abnormalities in the PI3K/Akt signaling pathway are significantly more likely to be associated with nodal metastases.
In a study published online July 24 in JAMA Surgery, researchers investigated fresh surgical specimens removed from 30 women with invasive ductal breast cancers (stages IA to IIIB) during mastectomy or lumpectomy.
Nine women with stem/progenitor cell mutations and 4 without had associated tumor in the lymph nodes (P = .001).
Of the 10 women with mutated stem/progenitor cells, 3 experienced disease progression after being treated with chemotherapy, hormone therapy, and a trastuzumab regimen. During a mean follow-up of 22 months, 2 women died of their disease; 1 has brain metastases.
None of the patients without stem/progenitor cell mutations have evidence of disease.
"The clinical relevance of this study is that breast cancers that contain stem/progenitor cells with PIK/Akt signaling pathway mutations represent a more aggressive disease," said lead author SuEllen Pommier, PhD, from the division of surgical oncology at Oregon Health & Science University in Portland.
"This is evidenced by the fact that these cancers were more likely to present with lymph node metastases," she told Medscape Medical News. "This finding was independent of size, grade, and hormone status of the tumor."
Mutations in Stem Cells
PIK/Akt signaling pathway defects occur in whole tumors. Studies of the incidence and clinical outcomes of such defects have reported varying results. "It could be that the variability in outcomes has more to do with the mutation status of the cancer stem/progenitor cells than of the tumor," said Dr. Pommier.
Because stem/progenitor cells make up only a small portion of the breast cancer cells, they need to be tested independent of the tumor. Because of their small numbers, they can be missed in whole-tumor testing, so the mutation status of cancer stem cells is difficult to determine definitely.
"We are currently evaluating the concordance of mutation status between whole tumors and breast cancer stem/progenitor populations," she said. The lack of concordance "underscores the need to test both the tumor and stem/progenitor cell populations. Both cell types provide crucial prognostic and treatment information."
If breast cancer stem cells are responsible for the initiation and metastasis, they could also orchestrate dormancy and recurrence of this disease, she continued. "Therefore, determining their defect at diagnosis can provide medical oncologists with relevant information for addressing these treatment issues. In our lab, we will continue to perform genetic testing on every qualifying breast cancer and their stem/progenitor cells."
"I believe with further testing and development, we can provide an improved prognostic tool, as well as valuable treatment information, to the medical community," Dr. Pommier added.
This study was supported by the Janet E. Bowen Foundation. The authors have disclosed no relevant financial relationships.
JAMA Surgery. Published online July 24, 2013. Abstract
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