The impact of HER2-Low expression in salivary duct carcinoma: Clinicopathologic features, survival outcomes, and association with androgen receptor-targeted therapy

• Published in: Oral oncology Vol. 165; p. 107280
• Main Authors: Kano, Satoshi, Kawakita, Daisuke, Honma, Yoshitaka, Takahashi, Hideaki, Nakaguro, Masato, Utsumi, Yoshitaka, Saigusa, Natsuki, Hanazawa, Toyoyuki, Tsukahara, Kiyoaki, Okada, Takuro, Okami, Kenji, Yamazaki, Keisuke, Ueki, Yushi, Saito, Yuki, Ozawa, Hiroyuki, Arai, Tomoyuki, Shimizu, Akira, Hanyu, Kenji, Iwaki, Sho, Imaizumi, Sae, Sakai, Akihiro, Yamauchi, Mayu, Tanaka, Ryoko, Sato, Yuichiro, Yamamura, Koji, Sekimizu, Mariko, Imanishi, Yorihisa, Hirai, Hideaki, Sato, Yukiko, Urano, Makoto, Yamamoto, Hidetaka, Fushimi, Chihiro, Matsuki, Takashi, Nagao, Toshitaka, Tada, Yuichiro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2025
• Subjects: Adult; Aged; Aged, 80 and over; Androgen receptor; Combined androgen blockade; Female; Head and neck cancer; Hematology, Oncology, and Palliative Medicine; HER2; HER2-low; Humans; Male; Middle Aged; Molecular Targeted Therapy; Otolaryngology; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Androgen - metabolism; Salivary duct carcinoma; Salivary Ducts - pathology; Salivary gland cancer; Salivary Gland Neoplasms - drug therapy; Salivary Gland Neoplasms - metabolism; Salivary Gland Neoplasms - mortality; Salivary Gland Neoplasms - pathology; BC; HER2-low; PR; IHC; DTX; HR; ORR; SD; CBR; SDC; PFS; Tmab; RFS; ISH; T-DXd; OS; CAB; CI; Salivary duct carcinoma; Combined androgen blockade; EN; EP; SGC; CR; AR; PD; Salivary gland cancer; Androgen receptor; NE; Head and neck cancer; CXPA; HER2; salivary gland carcinoma; extreme negative; stable disease; relapse-free survival; overall survival; carcinoma ex pleomorphic adenoma; extreme positive; hormone receptor; objective response rate; clinical benefit rate; in situ hybridization; progressive disease; trastuzumab deruxtecan; docetaxel; immunohistochemistry; partial response; non-extreme; progression-free survival; breast cancer; complete response; human epidermal growth factor receptor 2; trastuzumab; hazard ratio; confidence interval
• ISSN: 1368-8375; 1879-0593; 1879-0593
• DOI: 10.1016/j.oraloncology.2025.107280

•Of 526 salivary duct carcinoma (SDC) patients, 184 (35%) had HER2-low tumors.•Sex, M, histological origin, Ki67 and p53 differed between HER2-low and positive.•No differences in RFS or OS were observed for HER2 status in curative treatment cohort.•In AR-targeted therapy cohort, HER2-low had significantly better ORR and PFS than HER2-positive.•HER2-low can serve as a novel biomarker in patients with SDC. Recent advances in systemic therapy for salivary duct carcinoma (SDC) have been driven by the development of HER2- and androgen receptor (AR)-targeted therapies. Trastuzumab deruxtecan has proven effective not only in HER2-positive but also HER2-low breast and gastro-esophageal cancers. However, the significance of HER2-low expression in SDC remains unknown. This study aimed to investigate the clinicopathologic characteristics, prognostic implications, and impact on efficacy to AR-targeted therapy in HER2-low SDC. This was a multi-center, observational study. HER2 status was reclassified as follows: HER2-positive (IHC3+ or 2+/ISH+ ), HER2-low (IHC1+ or 2+/ISH-), and HER2-zero (IHC0). The subjects were compared in three groups: total population, curative treatment cohort, and AR-targeted therapy cohort. The total population consisted of 526 patients, of whom, 271 (52 %), 184 (35 %), and 71 (13 %) had HER2-positive, -low, and -zero tumors, respectively. Sex, M category, histological origin, Ki67, and p53 expression differed significantly between the HER2-low and HER2-positive cases. No differences in relapse-free or overall survival were observed for HER2 status in the curative treatment cohort; however, in the AR-targeted therapy cohort, the HER2-low group had significantly better response rates (41.6 % vs. 18.9 %, Odds ratio = 0.30, P = 0.012) and longer median progression-free survival (6.9 vs. 4.2 months, Hazard ratio = 1.61, P = 0.029) than those of the HER2-positive group. HER2-low showed different clinicopathologic features from HER2-positive cases, with no prognostic differences observed in patients who underwent curative treatment. Still, HER2-low may be associated with the efficacy of AR-targeted therapy.