BackgroundMetastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS “pathway” activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine.MethodsIn this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer.FindingsSIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases.InterpretationThe discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy.FundingThis work was supported by the (A.H. Tang); (MF14S-009-LS to A.H. Tang), and (CA140550 to A.H. Tang).

The coincidence of hyperthyroidism and thyroid carcinoma seldom occurs. Only few reports on functionally metastases of thyroid carcinoma have been published. We report a 59-year-old man who underwent subtotal thyroidectomy for toxic nodular goiter. Histological examination revealed a follicular thyroid carcinoma. After thyroidectomy and cervical lymphadenectomy the patient developed a strong hyperthyreosis. Scintigraphy showed strong radioiodine uptake in the sacrum. De-bulking resection of the metastasis followed by high-dose radioiodine treatment was performed. After radioiodine therapy the patient became euthyroid. Treatment of hyperthyreosis in metastatic thyroid cancer requires a multimodal therapeutic concept.

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