IMPORTANCE Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. OBJECTIVE To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. EXPOSURES Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. MAIN OUTCOMES AND MEASURES Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. RESULTS A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled.In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: β, −0.38; 95% CI, −0.55 to −0.21; P < .001; and S-IgG: β, −0.39; 95% CI, −0.54 to −0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-

Background: The prognostic value of stromal tumor-infiltrating lymphocytes (TILs) as a biomarker for triple-negative breast cancer (TNBC) has been extensively demonstrated in patients (pts) receiving (neo)adjuvant systemic therapy. In addition, several small studies suggest that a subset of pts with early-stage TNBC and high TILs have excellent long-term outcomes, even in the absence of systemic therapy [1-3]. However, data on the absolute risk of TNBC recurrence according to TIL levels in the absence of systemic therapy are limited and critical to inform the design of future systemic therapy de-escalation clinical trials. Methods: We conducted an individual patient data pooled analysis of 12 international cohorts of pts with TNBC treated with locoregional therapy but no systemic therapy. TNBC was defined as tumors with estrogen and progesterone receptor of &lt; 1% and HER2 negative (IHC 0, 1+ or IHC 2+ and FISH negative) per local evaluation. TILs were locally assessed in hematoxylin & eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group guidelines (www.tilsinbreastcancer.org). We used the Kaplan-Meier method to assess survival outcomes according to prespecified TIL thresholds: 30% and 50%. Confidence intervals (CI) for survival probabilities were calculated using a percentile bootstrap method. The primary endpoint was invasive disease-free survival (iDFS, STEEP 2.0 definition). Key secondary outcomes included recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS). Results: 1,835 pts diagnosed with TNBC between 1982 and 2017 who did not receive systemic therapy were included. The median age at diagnosis was 56 (IQR 38-71). Menopausal status was known in 1,184 women, of whom 78% were post-menopausal. The median tumor size was 2.0 cm (IQR 1.2-2.6). Most pts (87%) had no axillary lymph node involvement (N0). Most tumors were invasive ductal carcinoma (74%) and grade 3 (70%). The median level of TILs was 15% (IQR 5-40). The median duration of follow-up was 30.4 years (95% CI 29.9, 31.1). A total of 950 (52%) iDFS, 828 (45%) RFS, 767 (42%) DDFS events, and 604 (33%) deaths were observed. In multivariable analyses, higher TILs were independently associated with improved iDFS, RFS, DDFS, and OS beyond clinicopathological factors (likelihood ratio p&lt; 10e-6). Each 10% increment in stromal TILs was associated with an 8% (95% CI: 6-11), 10% (95% CI: 7-13), and 13% (95% CI: 10-15) reduction in the risk of experiencing an iDFS, RFS or DDFS event, and with a 12% (95% CI: 9-15) reduction in the risk of death. iDFS, RFS, DDFS and OS rates according to different TIL thresholds and nodal status are shown in the Table. Of note, the RFS estimates (which exclude second non-breast primaries and contralateral breast cancers) were consistently higher than the iDFS counterparts (which include both), consistent with a high rate of contralateral breast cancers and second primary tumors in this cohort. Notably, patients with node-negative—and especially stage I—TNBC with high TILs had excellent survival rates at 10-year follow-up. Conclusion: TILs are highly prognostic in pts with systemically untreated early-stage TNBC. Pts with pN0 (and especially stage I) TNBC with high TILs exhibited very favorable long-term outcomes even in the absence of systemic therapy. These data define the natural history of TIL-rich TNBC pts and are crucial to identifying the optimal patient population for future chemotherapy and immunotherapy de-escalation clinical trials. References: [1] Leon-Ferre et al, 2017, PMID: 28913760 [2] Park et al, 2019, PMID: 31566659 [3] de Jong et al, 2022, PMID: 35353548 Table 5 and 10-year survival endpoints according TIL level, nodal status, and stage Citation Format: Roberto A. Leon-Ferre, Sarah Flora Jonas, Roberto Salgado, Sherene Loi, Vincent De Jong, Jodi M. Carter, Torsten Nielson, Samuel Leung, Nazia Riaz, Giuseppe Curigliano, Carmen Criscitiello, Vincent Cockenpot, Matteo Lambertini, Vera Suman, Barbro Linderholm, John WM Martens, Carolien HM van Deurzen, Mieke Timmermans, Tatsunori Shimoi, Shu Yazaki, Masayuki Yoshida, Sung-Bae Kim, Hee Jin Lee, Maria Vittoria Dieci, Guillaume Bataillon, Anne Salomon, Fabrice Andre, Marleen Kok, Sabine Linn, Matthew P. Goetz, Stefan Michiels. Stromal tumor-infiltrating lymphocytes identify early-stage triple-negative breast cancer patients with favorable outcomes at 10-year follow-up in the absence of systemic therapy: a pooled analysis of 1835 patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD9-05.

Background: HER3 (ErbB-3) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases, and its overexpression is associated with poorer prognosis in several cancer types. It is unclear whether HER3 expression status changes in tumor tissue at relapse. The purpose of this study is to evaluate changes in HER3 expression between initial diagnosis and recurrence in gynecologic cancers. Methods: This retrospective study included gynecologic cancer patients with matched paired tissues at the time of initial diagnosis and at the time of recurrence between 1999 and 2019 at National Cancer Center Hospital, Japan. Immunohistochemical (IHC) staining for HER3 was performed using formalin-fixed paraffin-embedded specimens. The primary antibody was HER3/ErbB3 (D22C5) XP Rabbit mAb (Cell Signaling Technology). HER3-positive was defined as an IHC score of 2+ or 3+, and HER3-negative was an IHC score of 0 or 1+, scored according to HER2 testing guidelines for gastroesophageal cancer. The H-score (range, 0-300) was calculated using the following formula: 3X+2Y+Z, where X, Y, and Z are the percentage of tumor cells showing strong, moderate, and weak staining intensity. The difference in HER3 expression between initial diagnosis and recurrence was evaluated using the χ2 test. Results: Eighty-six patients with gynecologic cancers were included (40 ovarian; 32 endometrial; 14 cervical). In ovarian cancer, 67.5% and 80.0% of the patients were HER3-positive at initial diagnosis and recurrence, respectively. There was a statistically significant increase in H-Score at recurrence (p=0.004). The HER3-positive rate in patients with endometrial cancer increased from 46.9% at initial diagnosis to 68.8% at recurrence, and H-Score tended to increase at recurrence (p=0.08). Twelve of the 14 patients (85.7%) with cervical cancer were HER3-positive, both at initial diagnosis and at recurrence, and H-Score tended to increase at recurrence (p=0.19). The discordance rate of HER3 expression determination in samples at initial diagnosis and recurrence was 27.5%, 46.9%, and 14.3% for ovarian, endometrial, and cervical cancers, respectively. Conclusion: Our findings suggest that HER3 expression may increase at recurrence in patients with gynecologic cancers. HER3-targeted therapy may represent a promising option to overcome treatment failure and improve patient outcomes. Citation Format: Yuki Kojima, Kazuki Sudo, Hiroshi Yoshida, Shu Yazaki, Momoko Tokura, Shosuke Kita, Kasumi Yamamoto, Chiharu Mizoguchi, Hitomi S Okuma, Tadaaki Nishikawa, Emi Noguchi, Tatsunori Shimoi, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Kumiko Koyama, Maki Kobayashi, Tomoya Kakegawa, Yasuhiro Fujiwara, Kan Yonemori. Changes in HER3 expression profiles between initial diagnosis and recurrence in gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5083.

10626 Background: Patients with tumor are at high risk of severe COVID-19, and vaccination against SARS-CoV-2 is recommended. Impact of cancer treatment on immunogenicity has not been evaluated well. Methods: This prospective study was conducted to assess the seroconversion rate of SARS-CoV-2 vaccines among patients with cancer and hospital staff. Further, we focused on the difference among cancer treatment regimens. SARS-CoV-2 spike protein-specific IgG (S-IgG) were evaluated before the first vaccination, 1–3 months, 4–6 months, and 7–12 months after the second vaccination, and 1–3 months after the third vaccination. The primary endpoint was seroconversion rate measured 1–3 months after the second vaccination. Results: From April 2021 to November 2021, consent was obtained from 629 cancer patients and 210 hospital staff. Excluding missing data and withdrawal of consent, 590 cancer patients and 183 hospital staff without complications was analyzed. At 1–3 months after the second vaccination, S-IgG antibody concentration higher than the cut-off value (20 BAU/mL) was found in 96.1% (567/590) patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4–6 months after second vaccination, S-IgG antibody concentration higher than the cut-off value was found in 93.1% (461/495) patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). The significant difference in seroconversion rate between the two groups persisted even after 7-12 months. Patients undergoing treatment regimens such as platinum combination therapy (median: 423.7, 95% CI: 264.2–767.0, p = 0.003) and alkylating agent (median: 57.5, 95% CI: 5.4–748, p < 0.0001) among cytotoxic drugs, and PARP inhibitor (median: 264, 95% CI: 43–690.4, p = 0.0004), mTOR inhibitor (median: 227.4, 95% CI: 5.7–323.4, p = 0.0036), BCR-ABL inhibitor among drugs (median: 124.4, 95% CI: 0.0–288.9, p = 0.005) among target molecule drugs showed lower antibody titer compared to the no-treatment patients with cancer group. Conclusions: SARS-CoV-2 vaccine immunogenicity was low among patients with cancer compared to healthy control. Also, several treatment regimens were found to negatively impact immune response. Clinical trial information: UMIN000049403 , UMIN000049430 . [Table: see text]