Management of lymphedema is really a matter in patients with breast cancer.

Lymphedema is a prevalent complication affecting patients with breast cancer, greatly impacting their quality of life. This editorial describes diagnostic methods and therapeutic interventions for managing lymphedema in patients with breast cancer. Diagnosis relies on clinical evaluation and objective measures, including arm circumference and volumetric assessments, along with lymphoscintigraphy and ultrasonic measurements. Treatment primarily involves complex decongestive physical therapy, comprising manual lymphatic drainage, compression therapy, exercise, and meticulous skin care. These interventions aim to reduce swelling, alleviate discomfort, and prevent further complications. Additionally, lifestyle modifications such as avoiding extreme temperatures and maintaining proper hygiene are essential. Flavonoids can be used for drug therapy. Despite its prevalence, lymphedema often receives inadequate attention in clinical practice, emphasizing the importance of raising awareness and enhancing medical services for affected individuals. Clinicians play a pivotal role in educating patients about preventive measures and ensuring timely intervention. Overall, a comprehensive approach encompassing early diagnosis, multidisciplinary management, and patient education is essential to mitigate the burden of lymphedema in patients with breast cancer and improve their overall well-being.

Multidisciplinary Shared Decision Making for Fertility Preservation in Young Women With Breast Cancer.

PURPOSE: Fertility preservation (FP) is an important issue for young survivors of breast cancer. Although international guidelines recommend pre-treatment fertility counseling for women with breast cancer, there is no standardized protocol or referral system for FP in South Korea. There are also barriers to discussing FP that make patient-centered decision making difficult. This study aimed to develop a shared decision making program for FP and compare the rates of FP procedures between the usual care and shared decision making groups. We hypothesized that multidisciplinary shared decision making for FP would increase the rate of FP procedures and patient satisfaction. METHODS: The multidisciplinary shared decision making for FP in young women with breast cancer (MYBC) is a multicenter, clustered, stepped-wedge, randomized trial. A total of 1100 patients with breast cancer, aged 19-40 years, from nine hospitals in South Korea, will be enrolled. They will be randomized at the institutional level and assigned to usual care and shared decision making groups. Four institutions, each of which can recruit more than 200 patients, will each become a cluster, whereas five institutions, each of which can recruit more than 50 patients, will become one cluster, for a total of five clusters. The shared decision making groups will receive multidisciplinary programs for FP developed by the investigator. The primary outcome is the rate of FP procedures; secondary outcomes include fertility results, satisfaction, and quality of life. Outcomes will be measured at enrollment, treatment initiation, and the 1-, 3-, and 5-year follow-ups after starting breast cancer treatment. DISCUSSION: A multidisciplinary shared decision making program for FP is expected to increase fertility rates and satisfaction among young patients with breast cancer. This study will provide the evidence to implement a multidisciplinary system for patients with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05139641. Registered on December 1, 2021.

Clinical characteristics and prognosis of postpartum breast cancer.

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.

Breast Cancer Statistics in Korea, 2019.

This article provides an annual update of Korean breast cancer statistics, including the incidence, tumor stage, type of surgical treatment, and mortality. The data was collected from the Korean Breast Cancer Society registry system and Korean Central Cancer Registry. In 2019, 29,729 women were newly diagnosed with breast cancer. Breast cancer has continued to increase in incidence since 2002 and been the most common cancer in Korean women since 2019. Of the newly diagnosed cases in 2019, 24,820 (83.5%) were of invasive carcinomas, and 4,909 (16.5%) were of carcinoma in situ. The median age of women with breast cancer was 52.8 years, and breast cancer was most commonly diagnosed in the age group of 40-49 years. The number of patients who have undergone breast conserving surgery has continued to increase since 2016, with 68.6% of patients undergoing breast conserving surgery in 2019. The incidence of early-stage breast cancer continues to increase, with stage 0 or I breast cancer accounting for 61.6% of cases. The most common subtype of breast cancer is the hormone receptor-positive human epidermal growth factor receptor 2-negative subtype (63.1%). The 5-year relative survival rate of patients with breast cancer from 2015 to 2019 was 93.6%, with an increase of 14.3% compared to that from 1993 to 1995. This report improves our understanding of breast cancer characteristics in South Korea.

Prediction of Oncotype DX Recurrence Score Using Clinicopathological Variables in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PURPOSE: Oncotype DX (ODX) is a well-validated multigene assay that is increasingly used in Korean clinical practice. This study aimed to develop a clinicopathological prediction (CPP) model for the ODX recurrence scores (RSs). METHODS: A total of 297 patients (study group, n = 175; external validation group, n = 122) with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, T1-3N0-1M0 breast cancer, and available ODX test results were included in the study. Risk categorization as determined by ODX RSs concurred with the TAILORx study (low-risk, RS ≤ 25; high-risk, RS > 25). Univariate and multivariate logistic regression analyses were used to assess the relationships between clinicopathological variables and risk stratified by the ODX RSs. A CPP model was constructed based on regression coefficients (ß values) for clinicopathological variables significant by multivariate regression analysis. RESULTS: Progesterone receptor (PR) negativity, high Ki-67 index, and nuclear grade (NG) 3 independently predicted high-risk RS, and these variables were used to construct the CPP model. The C-index, which represented the discriminatory ability of our CPP model for predicting a high-risk RS, was 0.915 (95% confidence interval [CI], 0.859-0.971). When the CPP model was applied to the external validation group, the C-index was 0.926 (95% CI, 0.873-0.978). CONCLUSION: Our CPP model based on PR, Ki-67 index, and NG could aid in the selection of patients with breast cancer requiring an ODX test.

CORRIGENDUM: Correction of the first author's affiliation. Low incidence of lymph node metastasis in patients with microinvasive breast cancer: a Korean nationwide study.

[This corrects the article on p. 306 in vol. 102, PMID: 35800998.].

Risk factors for level V metastasis in patients with N1b papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence has increased. Lateral lymph node metastasis (LLNM) implies a worse prognosis than central lymph node metastasis, with a higher recurrence rate and decreased disease-free survival. The 2015 American Thyroid Association guidelines recommend compartmental node dissection in patients with LLNM to reduce the risk of recurrence and mortality. The purpose of this study was to identify the risk factors for level V lymph node (LN) metastasis in patients with N1b papillary thyroid cancer (PTC). METHODS: A total of 110 consecutive patients who underwent total thyroidectomy with lateral neck dissection for PTC between April 2016 and April 2022 were retrospectively enrolled. Based on level V metastasis, 94 patients were divided into two groups, and their clinicopathological characteristics were compared. Univariable analysis were used to assess the factors associated with level V metastasis. Spearman correlation analysis were used to assess the correlation between tumors and LN. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for the number of metastatic LNs at each level for level V metastasis. RESULTS: The number of metastatic LNs and lymph node ratio (LNR) in level II were significantly associated with level V metastasis (P = 0.011 and 0.001, respectively). The number of metastatic LNs in level II and those in the total number of levels correlated with the number of metastatic LNs in level V (rho = 0.331, 0.325, and P = 0.001, 0.001, respectively). The cutoff value for the number of metastatic LNs in level II was defined as 2.5 (area under the curve = 0.757, sensitivity = 50%, specificity = 82.5%, 95% confidence interval [CI] 0.626-0.889, P = 0.002). Simultaneous 3-level metastasis (level II, III, and IV) and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis (P = 0.003 and 0.002). CONCLUSIONS: The number of metastatic LNs and LNR in level II, simultaneous 3-level metastasis (level II, III, and IV), and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis. (P = 0.011, 0.001, 0.003, and 0.002, respectively). In the future, larger-scale multi-institutional studies were needed to find out predictors for level V metastasis.

Clinicopathological features and prognosis associated with breast cancer laterality: a nationwide study from the Korean Breast Cancer Society.

Purpose: Although breast cancer is known to show a left predominance, the clinical characteristics and causes underlying this finding remain unclear. In addition, no related studies on breast cancer laterality have been conducted in patients with breast cancer in Korea. Therefore, we aimed to analyze differences in breast cancer laterality and the associated clinicopathological characteristics and prognosis among Korean patients with breast cancer. Methods: We conducted a retrospective analysis using large-scale data on clinicopathological factors and prognosis differences related to breast cancer laterality from the Korean Breast Cancer Society Registration system. The left-to-right ratio (LRR) of breast cancer was calculated through binomial distribution, and factors related to breast cancer laterality were identified through logistic regression analysis. In addition, the differences in the survival rates for left and right breast cancers were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results: In 171,500 patients, the LRR was 1.031 (95% confidence interval, 1.022-1.041; P < 0.001). Multivariate analysis showed that the ratio of left breast cancer was related to age, body mass index (BMI), location, and human epidermal growth factor receptor 2 (HER2) status. The survival rate of patients with left and right breast cancers showed no significant difference. Conclusion: A large-scale analysis revealed a left predominance in breast cancer laterality in Korean patients. Over time, this predominance gradually decreased. Age, BMI, location, and HER2 status affected breast cancer laterality. However, while left breast cancer showed relatively aggressive characteristics, it was not associated with a difference in the survival rate.

Characteristics and Prognosis of Estrogen Receptor Low-Positive Breast Cancer.

PURPOSE: The updated American Society of Clinical Oncology/College of American Pathologists guideline for estrogen receptor (ER) testing recommends that breast cancer with ER expression in 1-10% of tumor cells should be reported as ER-low positive (ERlow), although limited data are available on the overall benefits of endocrine therapy. We investigated the clinicopathological characteristics and clinical outcomes of ERlow breast cancer and to compare them with those of ER-negative (ERneg) and ER-high (> 10% of tumor cells, ERhigh) breast cancers. METHODS: Consecutive patients with invasive breast cancer who underwent curative surgery between November 2007 and December 2014 were included. Clinicopathological characteristics and disease-free survival (DFS) of ERlow tumors were compared with those of ERneg and ERhigh tumors. RESULTS: Of the 2,309 cases included, 46 (2%), 643 (27.8%), and 1,620 (70.2%) were ERlow, ERneg, and ERhigh, respectively. ERlow tumors were associated with no special type of histology (p = 0.011), advanced pT (p = 0.017), pN (p = 0.009) and anatomic stages (p < 0.001), high grade (p < 0.001), negative/low progesterone receptor (PR) status (p < 0.001), human epidermal growth factor receptor 2 positivity (p < 0.001), high Ki-67 (p < 0.001), and recurrence (p = 0.006) compared to ERhigh tumors. DFS was significantly dependent on ER status, and ERlow tumors showed poorer DFS than ERhigh tumors (p = 0.001), however, there was no significant survival difference between ERlow and ERneg tumors. Furthermore, DFS in ERhigh patients was affected by hormone therapy (p < 0.001), while it was not affected in ERlow patients. CONCLUSION: Patients with ERlow breast cancer have clinicopathological characteristics that differ from those with ERhigh tumors. Although this study was limited by the small sample size of the ERlow group, no benefit from hormone therapy was observed in the ERlow group compared with the ERhigh group.

Low incidence of lymph node metastasis in patients with microinvasive breast cancer: a Korean nationwide study.

Purpose: Microinvasive breast cancer (MIBC) is an invasive carcinoma with a tumor dimension not exceeding 1 mm. Owing to its low incidence, the rate of axillary node metastasis and its management are not well established. The aim of this study was to assess the incidence of lymph node metastasis (LNM) and identify variables associated with LNM, as well as to evaluate the need for axillary staging in MIBC patients by analyzing nationwide data. Methods: The Korean Breast Cancer Society registry was searched to identify MIBC patients diagnosed between January 1996 and April 2020. Patients without neoadjuvant chemotherapy experiences, systemic metastasis, and missing or discordant data were eligible for the analysis. The incidence rate of LNM was determined, and variables associated with LNM were identified by multivariable regression analysis. Results: Of 2,427 MIBC patients identified, 98 (4.0%) had LNM and 12 (0.5%) had N2/3 disease. Type of breast operation (odds ratio [OR], 2.093; 95% confidence interval [CI], 1.332-3.290; P = 0.001), age (OR, 2.091; 95% CI, 1.326-3.298; P = 0.002), hormone receptor status (OR, 2.220; 95% CI, 1.372-3.594; P = 0.001), and lymphovascular invasion (OR, 11.143; 95% CI, 6.354-19.540; P < 0.001) were significantly related to LNM. Conclusion: The incidence of LNM in MIBC patients was only 4.0% in our study, suggesting that de-escalation of axillary surgical interventions could be carefully considered. The indications for axillary staging should be individualized considering tumor volume, age, hormone receptor status, and lymphovascular invasion to improve the quality of life of MIBC survivors.

Robot-assisted Nipple-sparing Mastectomy With Immediate Breast Reconstruction: An initial Experience of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 50.0 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

Recurrence prediction for breast phyllodes tumours: validation of the Singapore nomogram in Korean women.

AIM: The Singapore nomogram was developed to predict recurrence risk of phyllodes tumours (PTs) of the breast based on histological features of stromal atypia, stromal mitoses, stromal overgrowth and surgical margin status. We aimed to validate the utility of the Singapore nomogram in a Korean PT cohort. METHODS: One hundred and twenty-four patients with Korean PT who underwent surgical resection between 1996 and 2015 were included in this study. Pathology reports and slides were reviewed to obtain histopathologic features and acquire Singapore nomogram scores. The probability of concordance between predicted and observed survivals by means of the Singapore nomogram was evaluated using a concordance index (C-index). RESULTS: Of the 124 cases, 57 (46%) were diagnosed as benign, 50 (40.3%) as borderline and 17 (13.7%) as malignant. Recurrences occurred in 25 (20.2%) patients. Univariate analysis showed PTs with higher stromal mitotic counts, marked stromal cellularity, stromal overgrowth, positive surgical margin, marked stromal atypia or a malignant grade presented higher risks of recurrence. Multivariate analysis showed stromal mitoses and surgical margin status independently predicted recurrence-free survival. Patients with high nomogram scores were at greater risk of recurrence (HR=1.05, 95% CI: 1.02 to 1.07, p<0.001) with a C-index of 0.762. CONCLUSION: The Singapore nomogram provided a useful means of predicting PT outcomes in a Korean PT cohort.

Analysis of risk factors associated with survival in human epidermal growth factor receptor 2-positive ductal carcinoma in situ using Korean Breast Cancer Society Database.

PURPOSE: This study was performed to identify the risk of mortality in patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ductal carcinoma in situ (DCIS). METHODS: We selected 2,592 patients with HER2-positive DCIS from Korean Breast Cancer Society (KBCS) database between January 1997 and December 2019. Patients who received neoadjuvant chemotherapy were excluded. Logistic regression analysis was used to determine the association between clinical factors and overall death after adjusting for tumor and clinical characteristics. Mortality data were modified using the Statistics Korea data. RESULTS: Thirty deaths (1.2%) were identified out of 2,592 patients in the KBCS database. In the univariate logistic regression analysis, older age, higher body mass index (BMI), type of breast surgery (mastectomy), estrogen receptor-negative, progesterone receptor-negative, and exposure to endocrine therapy were significant clinical factors associated with death. In the multivariate analysis, age (hazard ratio [HR], 1.062; 95% confidence interval [CI], 1.015-1.111; P = 0.006), BMI (HR, 1.179; 95% CI, 1.032-1.347, P = 0.016), breast surgery type (mastectomy vs. lumpectomy; HR, 0.285; 95% CI, 0.096-0.844; P = 0.024), and endocrine therapy (HR, 0.314; 95% CI, 0.099-0.995; P = 0.049) were significant risk factors for mortality. CONCLUSION: Advanced age, higher BMI, mastectomy, and the absence of endocrine therapy were factors associated with poor survival of patients with HER2-positive DCIS. This finding requires further validation combined with additional analysis of large databases.

Comparison of clinicopathological characteristics and prognosis in breast cancer patients with different Breast Imaging Reporting and Data System categories.

PURPOSE: The Breast Imaging Reporting and Data System (BI-RADS) is a systematic and standardized scheme of the radiological findings of breast. However, there were different BI-RADS categories between breast cancers as the clinical characteristics in previous studies. We analyzed the association of BI-RADS categories with the clinicopathological characteristics and prognosis of breast cancer. METHODS: A total of 44,184 patients with invasive breast cancers assigned to BI-RADS category 3, 4, or 5 in preoperative mammography or ultrasonography were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society registration system. The difference in the clinicopathological factors and prognoses according to the BI-RADS categories (BI-RADS 3-4 and BI-RADS 5) were compared between the mammography and ultrasonography groups. Comparisons of the clinicopathological factors in both groups were made using logistic regression analysis, while the prognoses were based on the breast cancer-specific survival using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: The factors associated with BI-RADS were T stage, N stage, palpability, histology grade, and lymphovascular invasion in the mammography group; and N stage, palpability, histology grade, and lymphovascular invasion in the ultrasonography group. In the survival analysis, there were significant differences in the breast cancer-specific survival of the BI-RADS category groups in both of the mammography (hazard ratio [HR], 3.366; P < 0.001) and ultrasonography (HR, 2.877; P < 0.001) groups. CONCLUSION: In this study, the BI-RADS categories of preoperative mammography and ultrasonography of patients with invasive breast cancer were associated with prognosis and could be an important factor in making treatment decisions.

Immunohistochemical Expressions of Senescence-Associated Secretory Phenotype and Its Association With Immune Microenvironments and Clinicopathological Factors in Invasive Breast Cancer.

This study was undertaken to investigate immunohistochemical expression of the senescence-associated secretory phenotype (SASP) in invasive breast cancer (IBC) tissues and to determine relationships between SASP positivity and tumor microenvironments and the clinicopathological characteristics of IBC. Immunohistochemistry for senescence markers, that is, high mobility group box-1 (HMGB1), p16, p15, and decoy receptor 2 (DCR2), was performed in tissue microarrays of 1140 IBC samples. Cases positive for at least one of these four markers were considered SASP-positive. Relations between SASP and tumor characteristics, including immune microenvironments (stromal tumor-infiltrating lymphocytes [sTILs] density and numbers of intraepithelial CD103-positive [iCD103 + ] lymphocytes) and clinical outcomes were retrospectively evaluated. HMGB1, p16, p15, or DCR2 was positive in 6.7%, 26.6%, 21.1%, and 26.5%, respectively, of the 1,140 cases. Six hundred and five (53.1%) cases were SASP positive, and SASP positivity was significantly associated with histologic grade 3, high-sTIL and iCD103 + lymphocyte counts, absence of ER or PR, and a high Ki-67 index. Although SASP did not predict breast cancer-specific survival (BCSS) or disease-free survival (DFS) in the entire cohort, SASP positivity in luminal A IBC was associated with poor BCSS and DFS. However, patients with SASP-positive TNBC showed better survival than those with SASP-negative TNBC. In multivariate analysis, SASP positivity was an independent prognostic factor in both luminal A IBC and TNBC, although the effect on prognosis was the opposite. In conclusion, SASP would be involved in the modulation of immune microenvironments and tumor progression in IBC, and its prognostic significance depends on molecular subtype.

Response to neoadjuvant chemotherapy based on pathologic complete response in very young patients with ER-positive breast cancer: a large, multicenter, observational study.

BACKGROUND: In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. METHODS: We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups. RESULTS: The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. CONCLUSIONS: Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered. TRIAL REGISTRATION: Retrospectively registered.

Clinical impact of radioactive iodine dose selection based on the number of metastatic lymph nodes in patients with papillary thyroid carcinoma: A multicenter retrospective cohort study.

OBJECTIVE: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026). CONCLUSIONS: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors.

Analysis of the Molecular Signature of Breast Implant-Associated Anaplastic Large Cell Lymphoma in an Asian Patient.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)-a new category of anaplastic large cell lymphoma associated with textured breast implants-has a distinct variation in incidence and is especially rare in Asia. We report the first case of BIA-ALCL in Korea and present its histological and genetic characteristics. A 44-year-old female patient presented with a typical clinical course and symptoms, including breast augmentation with textured breast implants, late-onset peri-implant effusion, and CD30+ALK- histology, followed by bilateral implant removal and total capsulectomy. For histological analysis, we performed immunohistochemistry of the bilateral breast capsules. For transcriptome analysis, we identified highly upregulated gene sets employing RNA-sequencing and characterized the lymphoma immune cell components. In the lymphoma-associated capsule, CD30+ cells infiltrated not only the lymphoma lesion but also the peritumoral lesion. The morphologies of the myofibroblasts and vessels in the peritumoral lesion were similar to those in the tumoral lesion. We observed strong activation of the JAK/STAT3 pathway and expression of programmed death ligand-1 in the lymphoma. Unlike the molecular profiles of BIA-ALCL samples from Caucasian patients-all of which contained activated CD4+ T cells-the Asian patient's profile was characterized by more abundant CD8+ T cells. This study contributes to a better understanding of the pathogenesis and molecular mechanisms of BIA-ALCL in Asian patients that will ultimately facilitate the development of clinical therapies.

Impact of the Updated Guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer.

PURPOSE: In 2007, the American Society of Clinical Oncology and the College of American Pathologists had established a human epidermal growth factor receptor 2 (HER2) testing guideline, which was updated in 2013 and subsequently in 2018. We assessed the clinical impact of the recent update by comparing the in situ hybridization (ISH) results based on the 2007, 2013, and 2018 guidelines. METHODS: We assessed 2 cohorts. The first cohort included 1,161 primary invasive breast cancer (IBC) samples including 18 bilateral IBC cases, with both immunohistochemistry (IHC) and silver-enhanced ISH (SISH) results available for the HER2 status. The second cohort included 160 IBC cases with equivocal HER2 IHC, assessed using SISH. We retrospectively evaluated and compared the HER2 SISH results. RESULTS: There were 22 (1.9%) and 20 (12.5%) cases with altered SISH results according to the 2013 guidelines in cohorts 1 and 2, respectively. As per the 2018 guidelines, final HER2 statuses of 16 (1.4%) and 14 (8.5%) cases changed in cohorts 1 and 2, respectively. The 2013 guidelines increased the positive rate compared to the 2007 guidelines, in both cohorts (0.6% and 6.2%, respectively). Most equivocal cases in cohorts 1 (92.3%) and 2 (100%) as per the 2013 guidelines were reclassified as HER2-negative according to the 2018 guidelines. The 2018 guidelines increased the negative rates (1.3% in cohort 1 and 8.7% in cohort 2) and slightly decreased the positive rates (-0.2% in cohort 1 and -3.1% in cohort 2), compared to the 2013 guidelines. With each update, minor changes in the positive and negative rates were observed in whole breast cancer samples (cohort 1). However, the 2018 guidelines affected previously defined HER2-positive IBC with equivocal IHC results. CONCLUSION: Under the 2013 guidelines, the positive and equivocal cases increased. However, the 2018 guidelines eliminated ambiguous cases by reclassifying them as HER2-negative.