Surgical resection of breast cancers: Molecular analysis of cancer stem cells in residual disease
| Autor: | Arpana Naik, Rodney F. Pommier, Mary E. Condron, Cynthia M. Jackson, Nora E. Jameson, Patrick Muller, Kristen E. Limbach, Su Ellen J. Pommier, Rosemary E. Morgan, Jennifer L. Peckham |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Neoplasm Residual Class I Phosphatidylinositol 3-Kinases medicine.medical_treatment Estrogen receptor Breast Neoplasms 030230 surgery 03 medical and health sciences 0302 clinical medicine Breast cancer Cancer stem cell Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Medicine Humans Breast skin and connective tissue diseases Mastectomy Aged Aged 80 and over Chemotherapy business.industry CD24 Lumpectomy Middle Aged medicine.disease Neoadjuvant Therapy Treatment Outcome 030220 oncology & carcinogenesis Mutation Neoplastic Stem Cells Surgery Female Stem cell business |
| Zdroj: | Surgery. 165(5) |
| ISSN: | 1532-7361 |
| Popis: | Background Approximately 70% of breast cancer patients have residual disease after neoadjuvant chemotherapy. This study was designed to determine whether breast cancer cells with stemlike properties are present in residual disease after neoadjuvant chemotherapy and whether they exhibit oncogenic mutations. The presence of breast cancer cells with stemlike properties with specific mutations may help explain the poor prognosis associated with residual disease. Methods A total of 68 breast cancer specimens were collected at the time of mastectomy or lumpectomy. A total of 44 were chemotherapy naive and 24 were collected as residual disease after neoadjuvant chemotherapy. Tumor cells were collected by fluorescence-activated cell sorting, with breast cancer cells with stemlike properties specifically identified using breast stem cell associated antibodies. Whole tumor specimens and fluorescence-activated cell sorting breast cancer cells with stemlike properties were analyzed for genetic mutations, including PIK3CA. Results Breast cancer cells with stemlike properties, demonstrating EpCAM-positive, CD44-positive, CD49f ± , CD24 ± expression were present in chemotherapy-naive tumors and residual disease. In both chemotherapy-naive and residual disease specimens the highest frequency of PIK3CA mutations were detected in CD49f-CD24+ BCSCs (39% and 33%, respectively). PIK3CA mutations were detected in all stages of breast cancer (35%), in both chemotherapy naive (39%) and residual disease (29%) and in both estrogen receptor positive (41%) and negative tumors (14%) ( P = ns). Various PIK3CA mutations were identified in chemotherapy-naive specimens versus residual disease specimens in both patient-paired and unpaired breast cancers. Conclusion Breast cancer cells with stemlike properties with mutations in PIK3CA were present in chemotherapy-naive breast cancers and residual disease after neoadjuvant chemotherapy. These results demonstrate that neoadjuvant chemotherapy does not completely eradicate PIK3CA-defective breast cancer cells with stemlike properties. Although these findings may help explain the poor clinical outcomes in patients with residual disease, they also identify breast cancer cells with stemlike-property targets for therapies. |
| Databáze: | OpenAIRE |
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