Endogenous NIS Expression in Triple-Negative Breast Cancers

Abstract

NIS is strongly expressed in a significant proportion of triple-negative breast cancer cells, suggesting a potential role for NIS-directed (131)I-radioablative strategies in this patient population.

Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells

“…In subsequent studies it was demonstrated that NIS is frequently expressed during malignant transformation of mammary epithelial cells. Various groups have demonstrated high levels of NIS protein expression in human samples of mammary cancers with high frequency [4][5][6][7][8].…”

“…The high prevalence of NIS in human breast cancer and the demonstration of functionally active NIS expression in transgenic breast cancer mouse models such as the MMTV-PyVT, Ubi-hCGß and MMTV-neu model, suggest that endogenous mammary NIS expression may offer the possibility of NIS-targeted radioiodine imaging and therapy in breast cancer similar to its application in thyroid cancer [6][7][8]28]. However, currently available studies [5,6,8] suggest that stimulation of mammary NIS expression will be necessary to maximize diagnostic and therapeutic efficacy of NIS-mediated radioiodide accumulation in breast cancer, similar to TSH stimulation of thyroidal NIS, that is required for maximizing sensitivity and efficiency of radioiodine application in diagnosis and therapy of thyroid cancer.…”

“…These data indicate that NIS is frequently upregulated during malignant transformation in breast tissue [4][5][6][7]. Mammary NIS expression offers a powerful tool for selective breast cancer therapy based upon NIS-targeted application of radioiodine that has been used for over 60 years in the diagnosis and therapy of follicular cell-derived thyroid cancer as the most effective anticancer radiotherapy available today.…”

“…In view of these data, a clinical trial was performed by Nancy Carrasco's group, in which 27 women with breast cancer metastases were scanned with 99m Tc-pertechnetate uptake in only four tumors, while all of the 25 tumors revealed NIS mRNA expression [5]. In a recent study, positive NIS expression was demonstrated in 65% of 23 triple-negative breast cancers (estrogen-, progesterone-receptor negative and HER2/neu negative) by immunohistochemistry [6]. One patient with NIS-positive breast cancer underwent 123 I scintigraphy demonstrating a significant uptake compared to normal breast tissue.…”

“…The cumulative iodide uptake of 0.00131 % ID/ml, however, was not sufficient to achieve a therapeutic effect. Therefore, it is not unexpected that stimulation of functional NIS expression will be required to induce sufficiently high levels of iodide uptake in breast cancer which is comparable to the requirement of maximal TSH stimulation for optimization of diagnostic and therapeutic application of radioiodine in thyroid cancer [6][7][8].…”