Abstract 961: HER2-low expression in patients with advanced or metastatic solid tumors
Authors: Uzunparmak Burak , Haymaker Cara , Raso Gabriela , Zhu Chen , Masciari Serena , Wang Lei , Kirby Bryce , Lin Heather , Gorur Aysegul , Cimo Ann-Marie , Kennon Amber , Ding Qingqing , Palmieri Andrea , Urschel Gabriele Elizabeth , Yuan Ying , Feng Guoxin , Rizvi Yasmeen , Hussain Aisha , Subbiah Vivek , Yap Timothy Anthony , Rodon-Ahnert Jordi , Piha-Paul Sarina Anne , Hong David S. , Meric-Bernstam Funda , Dumbrava Ecaterina E. 
Published: April 2023

Introduction: HER2 protein expression by immunohistochemistry (IHC) has been the main testing method for breast and gastric cancers. Much remains unknown about the frequency of HER2-low (IHC 1+ or 2+) expression and the change of HER2 status from primary to metastatic tumor samples. There is limited data available about the HER2-low frequency in solid tumors beyond breast and gastric/gastroesophageal (GEJ) cancer.

Methods: HER2 IHC was performed in 923 patients (pts) with metastatic breast and 51 pts with gastric/GEJ cancers in CLIA-certified labs. We evaluated the HER2 IHC in paired primary and metastatic samples in breast cancer. We also assessed the HER2 status in non-breast, non-gastric/GEJ histologies. In available cases, concurrent HER2 genomic alterations were evaluated.

Results: A total of 867 pts with breast cancer had a definitive HER2 IHC score for their metastatic sample: 101 pts (11.6%) were 3+, 171 pts (19.7%) were 2+, 252 pts (29%) were 1+ and 343 (39.6%) had no HER2 expression. The HER2 IHC scores in metastatic samples as compared to primary was in concordance in 54.9% of cases, while HER2 3+ remained unchanged in 87.2%, kappa=0.85 with a 95% CI = (0.79, 0.91). In 48 cases with metastatic gastric/GEJ cancer, HER2 was: 3+ in 2 pts (4.2%), 2+ in 5 pts (10.4%), 1+ in 9 pts (18.8%) and 32 (66.7%) had no HER2 expression. In non-breast and non-gastric/GEJ cancers, HER2-low was found in 631 pts (33.5%) as shown in the table below. A total of 1,552 pts who had HER2 IHC also had genomic testing: 36 had HER2 activating mutations, 48 had HER2 amplification (amp) and 3 had HER2 amp and mutations. 22 of 33 pts with HER2 mutations (without amp) had HER2 IHC expression: 10 pts (30%) were 1+, 10 (30%) were 2+ and 2 (6%) were 3+.

Conclusion: Our results show that HER2-low expression is frequently found across tumor types and HER2 activating mutations are enriched in cancers where HER2 is expressed. These findings suggest that a high number of pts with solid tumors with HER2-low expression could potentially benefit from HER2 directed therapies.

HER2 expression in solid tumors Cancer Types HER2 expression levels (IHC) Total* 3+(N pts) 3+(%) 2+(N pts) 2+(%) 1+(N pts) 1+(%) 0 (N pts) 0 (%) Appendiceal 0 0 3 6 8 16 39 78 50 Cancer of Unknown Primary 2 4 8 15 15 28 29 54 54 Cholangiocarcinoma 5 4 15 12 35 29 67 55 122 Colorectal 19 3 46 8 118 20 394 68 577 Endometrial 16 13 49 39 10 8 52 41 127 Gallbladder 3 9 8 24 7 21 15 45 33 HNSCC 2 9 1 4 4 17 16 70 23 Salivary 6 13 10 21 14 29 18 38 48 Hepatocellular Carcinoma 0 0 8 25 6 19 18 56 32 Non-small cell lung cancer 6 3 31 15 68 33 100 49 205 Ovarian/Fallopian Tube 4 5 17 20 11 13 53 62 85 Pancreas 1 1 5 7 16 24 45 67 67 Prostate 0 0 0 0 4 13 27 87 31 Renal Cell Carcinoma 0 0 0 0 1 5 18 95 19 Sarcoma 0 0 1 3 1 3 35 95 37 Small Bowel Cancer 2 9 2 9 1 4 18 78 23 Thyroid 0 0 0 0 2 4 54 96 56 Urothelial Carcinoma 38 22 48 27 32 18 57 33 175 *more than 15 samples available; HNSCC=head and neck squamous cell carcinoma

Citation Format: Burak Uzunparmak, Cara Haymaker, Gabriela Raso, Chen Zhu, Serena Masciari, Lei Wang, Bryce Kirby, Heather Lin, Aysegul Gorur, Ann-Marie Cimo, Amber Kennon, Qingqing Ding, Andrea Palmieri, Gabriele Elizabeth Urschel, Ying Yuan, Guoxin Feng, Yasmeen Rizvi, Aisha Hussain, Vivek Subbiah, Timothy Anthony Yap, Jordi Rodon-Ahnert, Sarina Anne Piha-Paul, David S. Hong, Funda Meric-Bernstam, Ecaterina E. Dumbrava. HER2-low expression in patients with advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 961.