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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Robotic surgical systems enable surgeons to perform precise movement in the surgical field using high-resolution 3D vision and flexible robotic instruments. We aimed to evaluate the feasibility and safety of performing axillary lymph node dissection using a robotic surgical system in patients with node-positive breast cancer.Thirty-two women with breast cancer who underwent robot-assisted nipple-sparing mastectomy (RNSM) and level I/II axillary lymph node dissection were analyzed. Patients were divided into two groups: RNSM with conventional axillary lymph node dissection (CALND) vs. RNSM with robotic axillary lymph node dissection (RALND). Clinicopathological features and surgical outcomes were analyzed.The median age of the patients was 44 (range 20-59) years. Eleven patients underwent RALND. None of the clinicopathologic features differed between the two groups. There were no statistically significant differences in surgical outcomes, except for the final incision size, between the two groups. The proportion of cases with an incision ≤ 40 mm was 63.6% in the RALND group and 36.4% in the CALND group (p = 0.020).RALND can be safely performed in RNSM. RNSM with RALND is comparable to RNSM with CALND in terms of early surgical outcomes. The incision size can be reduced when using RALND.

Objectives: In South Korea, a significant number of patients with obstructive sleep apnea have benefited from the insured continuous positive pressure for sleep apnea as of 2018. However, there is limited information on public awareness of sleep apnea syndrome in the country. A nationwide survey was conducted to evaluate the current status of public awareness on the diagnosis and treatment of sleep apnea. Methods: We conducted an online survey using structured questionnaires on symptoms and knowledge of diagnosis and treatment modalities for sleep apnea. A total of 4,000 participants aged 21 to 69 were proportionally allocated according to the residential area, gender, and age group. Results: The STOP questionnaire, a screening tool for sleep apnea, revealed that 1,044 (21.6%) scored ≥2 points, 327 (8.1%) scored ≥3 points, and 64 (1.6%) scored 4 points. However, only 19 of the 1,044 patients were being treated for sleep apnea, and 13 had been using continuous positive airway pressure. For the diagnosis of sleep apnea, 1,318 participants (33.0%) responded that polysomnography was necessary. For sleep apnea treatment, 1,954 (48.9%) participants responded that lifestyle modification was the treatment of choice, while 1,036 (25.9%) chose continuous positive pressure. Conclusions: Although one-fifth were at high risk for sleep apnea, this disorder is still underestimated. Therefore, publicity and support are needed to improve public awareness of sleep apnea.

Sarcopenia is a major component of geriatric syndrome and associated with poor clinical outcomes and mortality. However, diagnosing sarcopenia in the very elderly is difficult, and data on its epidemiology and devastating effects in this group are scarce. Phase angle (PA) is measured using bioimpedance spectroscopy and known to reflect cellular integrity and health. This study aimed to clarify the impact of sarcopenia and PA on mortality risk in very elderly people living in long-term care facilities.This prospective cohort study enrolled elderly residents living in nine long-term care facilities. We collected the participants' data, such as body mass index (BMI), comorbidities and laboratory data, from September to October 2017 and mortality data until October 2019. Nutritional status was evaluated using the Mini Nutritional Assessment (MNA) score, and multifrequency bioimpedance spectroscopy was used to assess body composition including PA. Appendicular skeletal muscle mass was calculated using the body composition monitor-derived equation of Taiwan's researchers. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition (sarcopenia vs. normal group). We divided the participants into two groups according to the median PA value of 3.65° (high vs. low group) and performed multivariate regression analyses to verify the association with mortality risk according to sarcopenia diagnosis or PA group.A total of 279 elderly participants were enrolled; of them, 238 (85.3%) were diagnosed with sarcopenia according to EWGSOP2 guidelines. The median patient age was 83 years, 211 (75.6%) were female and the median BMI was 20.4 kg/mSarcopenia is prevalent among the very elderly patients in long-term care facilities. Sarcopenia and low PA are significantly associated with higher mortality risk.

There are limited studies on the association of COVID-19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID-19 vaccination and the occurrence of NA.We explored unexpected safety signals for NA related to COVID-19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database.On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (information component [IC]A weak association was observed between NA and COVID-19 vaccines. However, the risk did not surpass that of influenza vaccines.

Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

PurposeEstrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1-10%) of ER expression have been separately defined as ER Low Positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).MethodsRetrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative (ER-)).ResultsA total of 2162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2 (HER2), negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (P = 0.418).ConclusionERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

Since Korea implemented the Well-Dying Law in 2018, intensive, and end-of-life care have greatly changed. This study sought to determine whether there were any changes in the clinical aspects or appropriateness of intensive care unit admissions before and after the law was implemented.We performed a single-center retrospective study for 3 months with patients admitted to a medical intensive care unit before and after the law was implemented. We studied a total of 178 patients, divided pre-legislative group (83 patients) and a post-legislative group (95 patients).There were no significant differences in baseline characteristics, including age, sex, educational level, religion, economic status, and the Eastern Cooperative Oncology Group performance scale at the time of admission to the intensive care unit. There were no changes in the proportion of patients with terminal comorbidities, including malignancy and chronic lung diseases, with the exception of a decrease in patients with liver cirrhosis (12.1% in pre vs. 3.2% in post-legislative group, P=0.040). There were no differences in the APACHE II score at the time of admission, or in prognosis, including in-unit mortality (33.7 vs. 33.6%, P=0.53), in-hospital mortality (38.6% vs. 42.1%, P=0.73), and length of stay in the intensive care unit (IQR, 4.0-11.0 vs. 3.0-11.0 days, P=0.493). Last, no differences were observed in the appropriateness of admission, which was assessed by two separate intensivists, before and after implementing the law (P=0.646, and P=0.315, respectively).After the Well-Dying Law was implemented, there was a significant decrease in the number of liver cirrhosis patients admitted to the intensive care unit. No changes in other clinical characteristics, prognosis, and the appropriateness of admission were evident with the implementation of the law.

Purpose: The aim of this multicenter study was to investigate the malignancy risk of minimally cystic thyroid nodules (MCTNs) using cyto-histopathologic diagnoses as the reference standard.Methods: From June 2015 to September 2015, 5,601 thyroid nodules (≥1 cm) from 4,989 consecutive patients who underwent thyroid ultrasonography (US) at 26 institutions were retrospectively analyzed. Each thyroid nodule was categorized according to its cystic proportion: purely solid, minimally cystic (≤10%), and partially cystic (>10%). The malignancy risk of MCTNs was compared with those of purely solid nodules and partially cystic thyroid nodules (PCTNs). The malignancy risk of MCTNs was assessed according to echogenicity and the presence of suspicious US features.Results: The prevalence of MCTNs was 22.5%. The overall malignancy risk of MCTNs was 8.8%, which was significantly lower than that of purely solid nodules (29.5%) (P0.05). MCTNs were associated with a higher risk of malignancy in hypoechoic nodules than in isohyperechoic nodules and in nodules with suspicious US features than in those without suspicious US features (all P

We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.

We aimed to compare the performance of established inflammation and nutrition-based prognostic indices with a relatively novel index 'mid-upper arm circumference (MUAC)' in outpatients with advanced cancer.This study was a secondary analysis of a prospective cohort study that enrolled 200 outpatients with advanced cancer visiting a medical oncology clinic at a tertiary hospital. All patients were followed until death, and the Glasgow Prognostic Score (GPS), modified GPS (mGPS), Prognostic Nutritional Index (PNI), neutrophil/lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), and MUAC were compared by calculating the area under the receiver operating characteristic curves (AUROCs).The mean age of the patients was 64.4 years, 64.0% were male, and the median overall survival was 32.4 weeks [95% confidence interval (CI): 5.6-142.7]. Overall, all indices showed similarly high AUROCs for estimating 12-week (0.68 to 0.75) and 24-week survival (0.67 to 0.74). When confined to the GPS, mGPS, and MUAC, the AUROCs for 12-week survival were 0.75 (95% CI: 0.66-0.82), 0.74 (95% CI: 0.65-0.82), and 0.72 (95% CI: 0.64-0.79), respectively. For 24-week survival, the AUROCs were 0.70 (95% CI: 0.62-0.76), 0.67 (95% CI: 0.60-0.74), and 0.72 (95% CI: 0.64-0.79), respectively. MUAC had the highest specificity for estimating 12-week survival (86.0%), while GPS showed the highest sensitivity for estimating 12-week survival (81.1%).Inflammation and nutrition-based prognostic indices showed similar acceptable accuracies in estimating the 12- and 24-week survival of oncology outpatients. Notably, a simple and non-invasive index MUAC, showed comparable performance with established indices including GPS and mGPS.

Background The real-world risk of disease recurrence in patients with HER2-positive early breast cancer who achieved pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) and/or HER2-targeted therapy is unclear. This study aims to identify the patterns and risk factors of disease recurrence after NAC in patients with HER2-positive early breast cancer who achieved a pCR or not. Methods 930 HER2 positive early breast cancer patients who received NAC were identified in the Severance Breast Cancer Registry at the Yonsei Cancer Center and Gangnam Severance Hospital in Seoul, Republic of Korea, between 2006 and 2020. NAC included 3 regimens: only chemotherapy. (CTx), chemotherapy plus trastuzumab (CTx+H), and chemotherapy plus dual anti-HER2 therapy (TCHP). The pCR was defined as the absence of residual invasive cancer in the resected breast specimen and the axillary lymph nodes (ypT0/TisN0) after neoadjuvant systemic therapy. Recurrence of disease was defined as recurrence of ipsilateral locoregional invasive breast cancer, distant disease recurrence, or death. Results The median follow-up duration was 42.0 months (range 4-171), and median age was 51 years old (range 22-80). The rate of pCR was 52.2% (485/930). Depending on the achieved a pCR, the loco-regional recurrence rate was 4.0% (18/445) vs 1.0% (5/485), and the distant recurrence rate was 11.0% (49/445) vs 3.9% (19/445). Of the 79 patients who relapsed, 30.4% (n=24) had achieved a pCR and 69.6% (n=55) had residual disease. The 4-year recurrence risk was 6.9% for patients who achieved pCR versus 12.8% for those who did not (p Citation Format: Jee Hung Kim, Jii Bum Lee, Soong Joon Bae, Sung Gwe Ahn, Joon Jeong, Min Hwan Kim, Seul-Gi Kim, Gun Min Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Joohyuk Sohn. Pattern of recurrence after pathologic complete response after neoadjuvant chemotherapy in patients with early HER2-positive breast cancer: Real-world evidence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-14.

Background. Endocrine therapy plus CDK 4/6 inhibitors is the foremost treatment for hormone receptor (HR) positive metastatic breast cancers (mBC). Previously, we reported safety profiles of palbociclib use with grade 3 neutropenia in HR-positive mBC. Here, we investigated two cohorts’ patients who had received palbociclib with or without dose interruptions and/or reductions on afebrile grade 3 neutropenia in terms of efficacy outcomes. Patients and methods. The combined cohort of consecutive mBC patients who received palbociclib with letrozole in 1st line setting (in four major cancer centers in Republic of Korea) was reviewed. We classified patients into 4 groups: Group 1 (patients who maintained palbociclib dose on afebrile grade 3 neutropenia, representing limited dose modification scheme), Group 2 (patients who experienced any dose modification on afebrile grade 3 neutropenia, representing conventional dose modification scheme), Group 3 (patients without the event of afebrile grade 3 neutropenia), and Group 4 (patients who experienced only grade 4 neutropenia) within the first 5 cycles. The primary endpoint was PFS difference between Group 1 and Group 2, and secondary endpoints included PFS and overall survival difference in all groups, and safety profiles of each group. Results. A total of 434 eligible patients recruited from Jan 2017 to Sep 2020 were allocated into 4 groups; Group 1 (n=172, 40.1%), Group 2 (n=128, 29.5%), Group 3 (n=102, 23.5%), and Group 4 (n=30, 6.9%). The overall incidence of palbociclib dose reductions was 272 (62.7%) and dosing delay was 181 (42.2%) in all groups. The median time to first dose reduction for all eligible patients was 3 months (2-5 months) and the median time to second dose reduction was 9 months (2-30 months). At the 12th cycle of treatment, 70.5% (105/at-risk patients of 149) of Group 1 patients still remained on 125mg of palbociclib, whereas no patient was on 125mg dose level but 66.3% patients (65/at-risk patients of 98) were on 100mg in Group 2. At the median follow-up of 23.7 months (95% CI: 21.6-25.8), Group 1 patients showed significantly longer PFS than Group 2 patients (P-value = 0.036, 2-year PFS rate: 67.9% in Group 1 and 55.3% in Group 2). The OS between Group 1 and 2 was not significantly different. The favorable PFS trend of Group 1 over Group 2 was observed across all subgroups. The overall toxicity profiles were not significantly different between Group 1 and Group 2. Conclusion. Our study demonstrates that the clinical practice of limited dose modifications for palbociclib-related grade 3 neutropenia might have more therapeutic benefits than the conventional dose scheme without increasing toxicities. Permissive approach to afebrile grade 3 neutropenia and prospective clinical trials for this new dose scheme are warranted. Funding: This study was supported by a grant from Pfizer. Citation Format: Seul-Gi Kim, Min Hwan Kim, Sejung Park, Gun Min Kim, Jee Hung Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Jung Hwan Ji, Joon Jeong, Kabsoo Shin, Jieun Lee, Hyung-Don Kim, Kyung Hae Jung, Joohyuk Sohn. Efficacy of limited dose modifications for palbociclib-related grade 3 neutropenia in hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-09.

Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. Methods Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. Results In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. Conclusions On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.

Introduction: More than half of the results of axillary lymph node dissection followed by metastasis in sentinel lymph node(SLN) biopsy are negative. For deescalating axillary surgery, it is necessary to predict the non-SLN metastasis state, where metastasis was confirmed in the SLN biopsy. Method: Breast cancer patients with T1 and T2 stage were retrospectively reviewed from January 2008 to December 2016. A total of 818 patients underwent surgery as the primary treatment and the result of SLN biopsy was positive for metastasis. Patients who skipped SLN biopsy procedure and were proven metastatic axillary lymph nodes by needle-aspiration biopsy (NAB) were excluded. SLN was defined as lymph nodes detected by the dual method with hot-uptake by radioisotope and dyed by blue dye, or lymph nodes with palpable or suspected metastatic findings during SLN biopsy. Clinicopathological factors including and extra-nodal invasiveness were analyzed. Result: The median follow-up period was 73 months. Non-SLN metastasis was significantly seen in patients with older than 50 years, positive node metastases by preoperative NAB, high T stage, and extra-nodal invasion. In subgroup analysis, patients who underwent total mastectomy had the similar patterns of the increased risk of having non-SLN. Poor overall survival was observed in the patients with the presence of non-SLN metastasis. Conclusion: We confirmed predictive factors with a high probability of non-SLN metastasis. Axillary lymph node dissection cannot be overlooked in the patients proven the metastatic result of preoperative NAB. Citation Format: Jee Hyun Ahn, Suk Jun Lee, Jieon Go, Hyung Seok Park, Jee Ye Kim, Seung Il Kim, Byeong Woo Park, Seho Park. The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis [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 P3-05-56.

Background In HER2-positive breast cancer, pathologic complete response (pCR) has been known to be a surrogate marker for favorable prognosis after neoadjuvant chemotherapy. We aimed to identify the clinico-pathologic factors related to pCR in patients with HER2-positive breast cancer treated with neoadjuvant dual HER2-targeted therapy. Methods Two-hundred ninty-five patients with HER2-positive breast cancer who received neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) were included in this retrospective analysis. We assessed the association between age, clinical T, N stage, pathologic factors such as histologic grade, hormone receptor (HR), tumor-infiltrating lymphocytes, the membranous expression of HER2 protein evaluated by immunohistochemistry (IHC) and pCR. The fluorescent in situ hybridization (FISH) was performed in a tumor with HER2 score of 2+. Results Of the 295 patients, 195 (66.1%) achieved pCR (ypT0/is and ypN0). Besides, 240 (81.4%) patients were HER2 score of 3+, and 55 (18.6%) patients were HER2 score of 2+. The pCR was frequently observed in patients with HER2 score of 3+ (64 of 176 [73.3%]) than in those with HER2 score of 2+ (19 of 55 [34.5%]), regardless of HR status. After adjusting other clinicopathologic factors, the high HER2 protein expression was only an independent factor for pCR (adjusted OR 3.85, 95% CI, 1.66-8.91, p=0.002). Conclusions Our results suggest that high expression of HER2 protein assessed by IHC is important in predicting neoadjuvant TCHP response in HER2-positive breast cancer. Citation Format: Soong June Bae, Ji Soo Jang, Yoonwon Kook, Seung Ho Baek, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong. HER2-protein expression is a predictive marker for treatment response in patients with HER2-positive breast cancer who received neoadjuvant chemotherapy with dual HER2-blockade [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 P4-06-08.

The quality control of testing and inspection laboratories operated in Korea, the United States, and Canada was compared. The basic framework of on-site evaluation operated by each country was similar in terms of evaluation procedure, document evaluation, issuance of verification certificate, and follow-up management. For conducting on-site evaluation and granting the certificate, the preparation materials and evaluation processes are subdivided in Korea, while the dates of granting the certificate are restricted to four times a year in the United States. After receiving accreditation as a testing/inspection laboratories for the first time in Canada, follow-up management is divided into re-evaluation, verification evaluation, and monitoring evaluation.

Investigations for programmed cell death-1 (PD-1) blockade-induced hyperprogressive disease (HPD) have not been stringently conducted in patients with advanced gastric cancer (AGC). We explored the occurrence of HPD and its clinical implications in patients with AGC and treated with PD-1 inhibitors.We enrolled 169 patients with AGC and treated with either the PD-1 blockade (nivolumab or pembrolizumab; N = 112) or irinotecan monotherapy (N = 57) as a single agent. Tumour growth dynamics based on tumour growth kinetics and tumour growth rate (TGR) and time to treatment failure were analysed to define HPD. The incidence, clinical consequences and predictive markers of HPD were investigated.The optimal criteria for HPD were 4-fold increases in both tumour growth kinetics and TGR ratios and a 40% increase in TGR based on the analysis for patients treated with irinotecan. In total, 10.7% (12/112) of patients experienced HPD after PD-1 inhibitor treatment. Patients with HPD had both shorter progression-free survival (hazard ratio: 2.318; 95% confidence interval: 1.205-4.460) and overall survival (hazard ratio: 2.542; 95% confidence interval: 1.314-4.918) than patients with progressive disease without HPD, losing opportunities for subsequent systemic treatments. Although other variables including PD-L1 expression were not associated with the occurrence of HPD, hypoalbuminemia (lt;3.25 mg/dL) at baseline was significantly associated with the occurrence of HPD (P lt; 0.001) and inferior survival outcomes.HPD occurs in a proportion of patients with AGC and treated with PD-1 inhibitors. PD-1 inhibitor-induced HPD is associated with worse outcome, loss of eligibility for subsequent treatment and hypoalbuminemia, warranting further investigation.

Statement of problem Studies evaluating the accuracy of edentulous arch impressions encompassing conventional and digital methods are lacking. Purpose The purpose of this in vitro study was to evaluate 8 impression-making methods for edentulous arches and to determine the effects of using a 3-dimensionally printed polyetheretherketone (PEEK) scanning aid on the accuracy of intraoral scanners. Material and methods Three sets of edentulous arch typodonts were scanned with an industrial scanner as a reference. Subsequently, a scanning aid for the edentulous arch was individually designed on each reference scan dataset by using a 3-dimensional modeling software program and fabricated in PEEK with a 3-dimensional printer. Each typodont was scanned with 2 intraoral scanners 12 times, with and without the assistance of a scanning aid for the edentulous arch. Impressions were made with 4 different conventional impression materials (irreversible hydrocolloid, polysulfide, polyether, and polyvinyl siloxane)—12 times for each typodont—the casts were poured and digitized with a tabletop scanner. Each scan data set was superimposed over the corresponding scan data set, and the original and absolute distance values from the paired surface points were obtained to measure the trueness and precision. These were expressed by using the mean, median, root mean square, and (90 percentile-10 percentile)/2 of the absolute distance value (NMT) concepts, based on the raw data extraction protocol. A repeated-measures ANOVA followed by a post hoc Bonferroni test was conducted (α=.05). Results The impression-making methods did not show statistically significant differences (P>.05) for either trueness or precision, particularly when the median values of the original and absolute distance values from the paired surface points were chosen as the standard values. One of the intraoral scanners used exhibited significantly superior outcomes to conventional impression materials when scanned with the scanning aid for the edentulous arch for both trueness and precision when the mean, root mean square, and NMT concepts were applied (P Conclusions Intraoral scanners demonstrated accuracy comparable with that of conventional impression materials for making edentulous arch impressions, regardless of the concepts used to express the trueness and precision. The PEEK-based scanning aid for the edentulous arch did not improve the accuracy of the intraoral scanners; however, its application resulted in higher accuracy compared with that of conventional impression materials.

Background: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients.Methods: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma.Results: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; PTERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences.Conclusion: This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

This article presents a latent class model for multilevel data to identify latent subgroups and estimate heterogeneous treatment effects. Unlike sequential approaches that partition data first and then estimate average treatment effects (ATEs) within classes, we employ a Bayesian procedure to jointly estimate mixing probability, selection, and outcome models so that misclassification does not obstruct estimation of treatment effects. Simulation demonstrates that the proposed method finds the correct number of latent classes, estimates class-specific treatment effects well, and provides proper posterior standard deviations and credible intervals of ATEs. We apply this method to Trends in International Mathematics and Science Study data to investigate the effects of private science lessons on achievement scores and then find two latent classes, one with zero ATE and the other with positive ATE.

To determine the sensitivity and specificity of cutaneous amyloid deposition in relation to patient-reported measures in the earliest disease stage of hereditary ATTR amyloidosis (ATTRv).In a cross-sectional study, we analyzed 88 individuals with TTR mutations, 47 of whom were in the earliest disease stage and without clinically evident neuropathy, 12 healthy controls, and 13 disease controls with diabetes. All participants' neuropathy symptoms and signs were assessed using validated patient and clinician-reported measures and 3-mm skin punch biopsies were immunostained using protein gene product 9.5 and Congo Red.Amyloid can be detected in the earliest disease stages in up to 86% of patients with ATTRv amyloidosis. Amyloid was not detected in healthy individuals or individuals with diabetic peripheral neuropathy supporting a sensitivity of 86% and a specificity of 100%. The cutaneous deposition of amyloid correlates with neuropathy sensory symptoms, measured with the Neuropathy Total Symptom Score-6 (R = 0.46, p 0.01); pain measured with the Brief Pain Symptom Inventory (R = 0.44, p 0.05); autonomic symptoms, measured with the Boston Autonomic Symptom Questionnaire (R = 0.38, p 0.05); and quality of life measured with the Norfolk Diabetic Neuropathy Quality of Life Questionnaire (R = 0.44, p 0.05). Individuals with amyloid deposition were more likely to have sensory symptoms, pain, autonomic impairment, and reduced quality of life than ATTRv patients without amyloid deposition.These findings have implications for understanding the earliest manifestations of the clinical phenotype of ATTRv-associated neuropathy, for the pathophysiological construct of disease staging, and for timing the introduction of disease-modifying therapy.