Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma–related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma–related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non–ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.

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&lt;Background&gt; The Clinical Treatment Score post-5 years (CTS5) is a prognostic tool to estimate the residual risk of distant recurrence (DR) after 5 years of endocrine therapy in postmenopausal women with estrogen receptor (ER)-positive breast cancer. (J Clin Oncol, 2018; 19: 1941-1947). CTS5 might be useful to decide the indication of extended adjuvant endocrine therapy after 5years. &lt;Purpose&gt; This study was conducted to elucidate the usefulness of CTS5 for the prediction of late DR in postmenopausal women with ER-positive early breast cancer treated in our department. &lt;Patients and Methods&gt; CTS5 was calculated in 377 postmenopausal patients with ER-positive breast cancer who underwent surgery between 2003 and 2009. They had received 5-year adjuvant endocrine therapy without DR. CTS5 is stratified into three groups; low, intermediate and high risk of DR. The relationships between CTS5 and the clinicopathological characteristics and prognosis were evaluated. &lt;Results&gt; According to CTS5, 202 (53.6%), 104 (27.6%) and 71 (18.8%) patients were divided into low, intermediate and high-risk of late DR groups. In the CTS5-high risk group, significantly more positive lymph nodes (p&lt;0.0001), larger tumor size (p&lt;0.0001), higher histological grade (p&lt;0.0001), more administration of adjuvant chemotherapy (p&lt;0.0001), more administration of adjuvant endocrine therapy of Aromatase inhibitor (AI) (p=0.0029), more visceral distant metastasis (p=0.0029), lower ER expression (p=0.0064) were observed. Significantly lower incidence of DR was observed in CTS5-low risk group. Thus, CTS5 was significantly prognostic for late DR. Intriguingly, in the CTS5-low risk group, administration of endocrine therapy of AI (p=0.0023), lower histological grade (HG1, 2; p=0.0011), ER high expression (TS; 6-8 p=0.0002), and positive PgR (p=0.0007) were significantly better DR-free survival (DRFS). &lt;Conclusion&gt; CTS5 demonstrated clinical validity for predicting late DR in this study cohort. IN the CTS5-low risk group, the incidence of late DR was significantly lower than that of in CTS5-intermediate or high risk group. The low CTS5 might be useful to decide the indication of 5-year adjuvant endocrine therapy in the postmenopausal patients with ER-positive early breast cancer. Citation Format: Wakako Tajiri, Azusa Sugii, Hideki Ijichi, Hiroki Ueo, Chinami Koga, Yoshiaki Nakamura, Masahiro Okamoto, Kennichi Taguchi, Eriko Tokunaga. Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-20.