Abstract P1-09-21: Clinical evaluation of miR-100 as a predictor of endocrine-responsiveness in hormone-receptor positive breast cancer
| العنوان: | Abstract P1-09-21: Clinical evaluation of miR-100 as a predictor of endocrine-responsiveness in hormone-receptor positive breast cancer |
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| المؤلفون: | G Zucchini, Di Virgilio, Annalisa Petrelli, L Martincich, A. Nuzzo, Marilisa Cargnelutti, Rossella Martinello, Riccardo Ponzone, Anna Sapino, Ivana Sarotto, Silvia Giordano, Franziska Kubatzki, Filippo Montemurro |
| المصدر: | Cancer Research. 77:P1-09 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, Breast cancer, business.industry, Hormone receptor, Internal medicine, Medicine, Endocrine system, business, medicine.disease, Clinical evaluation |
| الوصف: | Background: Micro RNAs (miRNAs) are short, non-coding RNA molecules that act as negative regulators of gene-expression, mainly at the post-transcriptional level. Alterations in miRNA functions have been implicated in a variety of human diseases, including cancer We demonstrated that the ectopic expression of miR-100 in cancer stem cells (CSCs) derived from aggressive, basal-like BC (HRs and HER2 negative) caused loss of stemness and the acquisition of a hormone receptor positive and endocrine treatment sensitive phenotype (Petrelli et al, Oncotarget 6;2315-30, 2015). We therefore sought to study whether miR-100 is a determinant of the endocrine-responsive phenotype in HR-positive BC patients (pts). Methods: Women with newly diagnosed, estrogen-receptor and/or progesterone-receptor positive, HER2 negative BC were eligible for this study. Treatment consisting of tamoxifen for pre-menopausal and letrozole for post-menopausal pts was administered daily for 21 days (+/- 3 days) before breast surgery. MiR-100 levels in pre-treatment tumor biopsies, measured as fold-change with respect to a reference RNA and transformed to the natural logarithms to normalize the data, were correlated with proliferative response to endocrine therapy, as measured by Ki67 expression in the final surgical specimen. The primary end-point was a complete proliferative response (CPR), defined as a post-treatment Ki67≤1%. Additionally, we considered a “post-hoc” composite endpoint where response was defined as a post treatment Ki67 Results: A total of 42 pts were evaluable for miR-100 levels and response to endocrine therapy. Median ER and PgR expression was 99% (58%-99%) and 96% (0-99%) respectively. Median pre-treatment Ki67 was 18% (5-76%). Thirty-one tumors were ductal carcinomas, 9 were lobular and 2 were “other” histotypes. The median (range) miR-100 values in pre-treatment specimens was 2.253 (0.460-3.750). After treatment, median Ki67 was 4% (1%-46%) and the median percentage variation with respect to baseline values was -74% (0% to -94%). A CPR was observed in 5/42 pts (12%, 95% C.I. 5%-25%). The median miR-100 levels in responders and non-responders were 3.058 and 2.198, respectively (p = 0.03). Logistic regression analysis showed that each unit increase in miR-100 was associated with a 7-fold increase in the likelihood of a CPR (OR 7.056, 95% C.I. 1.103-45.141, p = 0.04). Considering the composite end-point, 17/42 pts (40%, 95% C.I. 27%-56%) were considered responders. Median miR-100 levels in responders and non-responders were 2.427 and 1.956, respectively (p = 0.05). Conclusions: preliminary results of this prospective clinical trial suggest that miR-100 can be a modulator of the endocrine-responsive phenotype in post-m pts with HR-positive breast cancer. The study is completing its target accrual and an investigation of miR-100 targets is being conducted. GZ and AP contributed equally to this work. Supported by Associazione Italiana per la Ricerca Sul Cancro (Investigator Grant IG-2013 Ref. 14451). Citation Format: Zucchini G, Petrelli A, Kubatzki F, Cargnelutti M, Di Virgilio MR, Sarotto I, Martincich L, Ponzone R, Martinello R, Sapino A, Nuzzo A, Giordano S, Montemurro F. Clinical evaluation of miR-100 as a predictor of endocrine-responsiveness in hormone-receptor positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-21. |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.sabcs16-p1-09-21 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ac6f0f3282e0ca5137b0f80d70efafcb https://doi.org/10.1158/1538-7445.sabcs16-p1-09-21 |
| رقم الانضمام: | edsair.doi...........ac6f0f3282e0ca5137b0f80d70efafcb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/1538-7445.sabcs16-p1-09-21 |