Somatostatin receptor SSTR2A and SSTR5 in neuroendocrine breast cancer

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1 Somatostatin receptor SSTR2A and SSTR5 in neuroendocrine breast cancer Robert Terlević, MD Melita Perić Balja, MD Davor Tomas, MD, PhD Božo Krušlin, MD, PhD Faruk Skenderi, MD, PhD Semir Vranić, Md, PhD Alma Demirović, MD, PhD Ljudevit Jurak Department of Pathology, University Hospital Center Sestre milosrdnice, Zagreb, Croatia Pula General Hospital, Pula, Croatia College of Medicine, Qatar University, Doha, Qatar Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina ECP Bilbao 2018, September

2 Enterprise Interest No disclosures.

3 Outline Neuroendocrine breast cancer: an overview Somatostatin receptors as potential therapeutic targets Materials and methods Results Conclusion

4 Neuroendocrine breast cancer (NBC): an overview 1/2 Definition (WHO2012): breast cancer with any neuroendocrine component: Well differentiated (carcinoid-like, very rare) Poorly differentiated/small cell (SCLC-like, also rare) Invasive carcinoma with neuroendocrine component (mostly NST, mucinous and solid papillary) Previous WHO definition (2003): at least 50% neuroendocrine component Solid, large cell, small cell

5 Neuroendocrine breast cancer (NBC): an overview 2/2 Molecularly distinct from NST breast cancer Incidence <1-20%: Lack of uniform diagnostic criteria (no cut-off for IHC diagnosis) Independent adverse prognostic factor (reduced DFS vs NST) Small cell worse than rest (high Ki-67) NBC not mentioned in official therapeutic guidelines (Bogina et al., 2016; Inno et al., 2016)

6 Somatostatin receptors (SSTR) as potential therapeutic targets 1/2 Well studied in gastroenteropancreatic NETs 5 known SSTRs (1-5) SSTR2A and SSTR5 IHC correlate best with scintigraphy SUV SSTR2A membrane staining, SSTR5 cytoplasmic (Kaemmerer et al. 2012, Volante et al. 2007)

7 Somatostatin receptors (SSTR) as potential therapeutic targets 2/2 Well established in gastrointestinal neuroendocrine tumors (NETs): Somatostatin analogs for G1/G2 lesions: antiproliferative effect Peptide receptor-targeted radionucleotide therapy (PRRT) for systemic disease Case report evidence of PRRT efficacy in systemic NBC Third line therapy Biochemical response and shrinkage of liver masses SSTR detected in vivo by scintigraphy (Oberg et al., 2012; Savelli et al., 2012)

8 Materials and methods 1/2 31 retrospective cases of primary NBC ( ) Histological diagnosis, confirmed by IHC Pre-2012 cases with 50% threshold SSTR2A and SSTR5 immunohistochemistry (Abcam, USA) Single representative block for each case Scored by consensus of 3 independent pathologists

9 Materials and methods 2/2 Modified immunoreactivity score of Remmele and Stanger (IRS): % of positive cells multiplied by intensity of staining Divided into 4 classes Both membranous and cytoplasmic % positive cells: 0 = no positive cells 1 = <10% positive cells 2 = 10-50% positive cells 3 = 51-80% positive cells 4 = >80% positive cells Intensity of staining: 0 = no colour reaction 1 = mild reaction 2 = moderate reaction 3 = intense reaction IRS class 0-1 = negative 2-3 = positive, weak 4-8 = positive, mild 9-12 = positive, strong (Kaemmerer et al., 2012)

10

11 Results 1/2 Mean patient age = 67 yr Mean tumor size= 11 mm Median grade = 2 Hormonal status: 25 ER+/Her2-15 with Ki-67>14% 3 ER+/Her2+ 3 ER-/Her2- SSTR2A IRS class % SSTR5 IRS class % Negative Positive, weak Positive, mild Positive, strong Total

12 Results 2/2 SSTR2A: 74% positive, mostly weak SSTR5: 81% positive, mostly weak No strong reactions: antibody differences? 3 double negative cases: 1 ER-/Her2-2 ER+/Her

13 Conclusion First work analyzing SSTR IHC expression in NBC Both SSTR2A and SSTR5 IHC were expressed in our series Weak expression most common Modified IRS scoring system useful and easy to use Lack of uniform diagnostic criteria risk of underdiagnosing NBC Larger series including metastatic disease needed Possible future therapeutic potential PRRT Somatostatin analog antiproliferative therapy?

14 Thank you for your attention! Zmlinar.com

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