Incidence and risk factors of breast cancer-related lymphedema in Korea: A nationwide retrospective cohort study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). METHODS: Patients with newly diagnosed breast cancer who underwent breast surgery from January 1, 2017 to December 31, 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer (breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy(MRM)). The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment and comorbidities. RESULTS: The final cohort of operation subjects that satisfied the inclusion criteria was 34,676. BCRL occurred in 4,242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), MRM (28.5%) with an incidence of 40.8, 132.2, 55.8 and 171.8 per 1,000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas and hyperlipidemia were identified as risk factors. CONCLUSION: In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Adherence to the American Cancer Society guidelines on nutrition and physical activity for cancer survivors and biomarkers of inflammation among breast cancer survivors.

OBJECTIVES: This study investigated whether adherence to the overall lifestyle recommendations in the American Cancer Society (ACS) guidelines on nutrition and physical activity for cancer survivors was associated with inflammation in breast cancer survivors. METHODS: The study included 409 women who had undergone breast cancer surgery at least 1 year before enrollment. A generalized linear model was used to estimate the least square means and 95% confidence intervals of plasma levels of inflammatory markers according to lifestyle factors defined in terms of adherence to the ACS guidelines. RESULTS: Higher overall adherence scores were associated with lower levels of high-sensitivity C-reactive protein (hs-CRP) (p for trend=0.015) and higher levels of adiponectin (p for trend=0.009). Similar significant associations of hs-CRP (p for trend= 0.004) and adiponectin (p for trend=0.010) levels were observed with the score for the body mass index (BMI) component of the adherence score. A higher diet component score was associated with a higher adiponectin level (p for trend=0.020), but there was no significant association for the physical activity component score. CONCLUSIONS: The present study's findings suggest that maintaining a healthy lifestyle according to the ACS guidelines was associated with beneficial effects on inflammatory marker levels, especially hs-CRP and adiponectin, among breast cancer survivors. Among the 3 components of lifestyle guidelines, the BMI component exhibited the most similar tendency to the overall adherence score in relation to inflammatory indicators. Further prospective and intervention studies are needed to investigate longitudinal associations between lifestyle factors and inflammatory markers among breast cancer survivors.

Dietary Isoflavone Intake and Breast Cancer Prognosis: A Prospective Analysis and Meta-Analysis.

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60-2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67-0.98) for recurrence and 0.85 (0.76-0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation.

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.

A Comparison of the Prognostic Effects of Fine Needle Aspiration and Core Needle Biopsy in Patients with Breast Cancer: A Nationwide Multicenter Prospective Registry.

(1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA (n = 8027) and CNB (n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors.

The prognosis of NX stage in patients with pT1 papillary thyroid cancer who underwent lobectomy.

Lymph node (LN) metastasis is known to impact the prognosis of patients with well-differentiated thyroid cancer. Herein, we aimed to determine the effect of NX stage on the prognosis of patients with papillary thyroid cancer who underwent thyroid lobectomy. We initially selected 1257 patients who underwent thyroid cancer surgery from 2012 to 2015. Of the 1257 patients, we included 556 in the analysis, excluding patients diagnosed with other types of thyroid cancer, those who underwent total or completion thyroidectomy, and those diagnosed with LN metastasis prior to surgery. The median follow-up time was 61.8 months (range: 12.3-108.9 months). After dividing the patients into N0, N1, and NX stage groups, we performed univariate and multivariate analyses. The 5-year recurrence-free survival (RFS) was analyzed using R version 3.2.5. The mean patient age was 45.0 ± 10.9 years. Of the 556 patients, 336 patients (60.4%) were diagnosed with N0 stage, 134 (24.1%) were N1 stage, and 86 (15.5%) were NX stage. Univariate and multivariate analyses were performed to identify prognostic factors for RFS. Considering gender, age, tumor size, surgery types, extrathyroidal extension, multifocality, and recurrence, no statistically significant differences were noted between the 3 groups. The 5-year RFS rates were 98.8%, 95.5%, and 97.6% for N0, N1, and NX groups, respectively, without significant differences between the 3 groups (P = .56). Considering the T1b stage, the 5-year RFS rates were 100%, 93.1%, and 93.7% in the N0, N1, and NX groups, respectively, with a statistically significant difference between the 3 groups (P = .018). Accordingly, the NX status cannot be deemed a prognostic factor for RFS in patients with papillary thyroid cancer who underwent thyroid lobectomy. However, the benefit of prophylactic central-LN dissection should be considered in patients with well-differentiated thyroid cancer diagnosed with T1b stage.

Epidemiology of Second Non-breast Primary Cancers among Survivors of Breast Cancer: A Korean Population-Based Study by the SMARTSHIP Group.

PURPOSE: This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer. Materials and Methods: Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis. RESULTS: The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02). CONCLUSION: Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient's age at IBC diagnosis, income level, and a receipt of systemic treatments.

Associations of body mass index and weight change with circulating levels of high-sensitivity C-reactive protein, proinflammatory cytokines, and adiponectin among breast cancer survivors.

AIM: This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea. METHODS: A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high-sensitivity C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and adiponectin. A summary z-score was calculated by summing up the z-scores of each biomarker. The least-square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model. RESULTS: Participants with a BMI ≥27.5 kg/m2 at the study enrollment and at diagnosis were significantly associated with elevated summary z-scores compared to those with a BMI < 23 kg/m2 ; the ORs (95% CIs) were 5.42 (2.15-13.71) for current BMI and 3.66 (1.68-7.98) for BMI at diagnosis, respectively. Additionally, a weight loss > 5% since diagnosis was associated with a lower prevalence of high summary z-scores; the OR (95% CI) was .20 (.08-.52) compared to a stable weight. CONCLUSIONS: A high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers.

Characteristics and chronologically changing patterns of late-onset breast cancer in Korean women of age ≥ 70 years: A hospital based-registry study.

BACKGROUND: Women from Asian and western countries have vastly different ages of onset of breast cancer, with the disease tending to occur at an older age in the West. Through an investigation of the patterns of old-onset breast cancer (OBC) in Korean women, we aimed to identify the characteristics of Korean OBC and evaluate whether these patterns are changing in relation to increasing westernization. METHODS: This study retrospectively evaluated 102,379 patients who underwent surgical treatment of primary breast cancer between January 1, 2000 and December 31, 2013 in Korea. We used hospital -based breast cancer registry and analyzed data from these patients using multiple linear regression analysis to compare the characteristics and chronologically changing patterns between OBC (70 years of age or older) and non-OBC (40-69 years of age) patients in Korea. RESULTS: A total of 6% of the 102,379 patients had OBC. Overall, OBC had more favorable biological features, such as a higher incidence of luminal A subtype, than did non-OBC, except for a higher incidence rate of triple-negative breast cancer (TNBC). However, OBC also presented with a higher overall disease stage, including higher T and M stages. Although the incidence rates of both OBC and non-OBC have increased overtime, the relative proportion of OBC patients has slightly increased, whereas that of non-OBC has slightly decreased. The increase in the incidence of both OBC and non-OBC was primarily due to the luminal A subtype. CONCLUSIONS: Based on a hospital-based registry, overall, Korean OBC had favorable biological features but showed a higher rate of TNBC and advanced cancer stages. The incidence trend of breast cancer in Korea is slowly shifting toward an older age at onset, largely due to the luminal A subtype. Our results may provide novel insights into OBC in Asia, and aid in the development of optimal management of the disease in Asia. TRIAL REGISTRATION: Retrospectively registered.

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.].

Survival of women with pregnancy-associated breast cancer according to clinical characteristics: A propensity score matching study.

In recent years, postponing childbearing has increased the prevalence of pregnancy-associated breast cancer (PABC). PABC has a poorer prognosis than breast cancer not associated with pregnancy (non-PABC) due to delayed diagnosis and aggressive subtype. Additionally, pregnancy itself predicts a poor prognosis; but, this is a subject of debate. Thus, we analyzed the effects of known prognostic factors and pregnancy on the prognosis of PABC. We retrospectively analyzed women aged 20 to 49 years who were diagnosed with breast cancer (BC) between 1989 and 2014. Patients were distributed into PABC and non-PABC groups, and 1:4 propensity score matching was performed to adjust for baseline characteristics. Primary endpoints were overall survival (OS) and BC-specific survival (BCSS). Secondary endpoint was the difference in prognosis according to BC subtype. Of the 34,970 recruited patients with BC, 410 (1.2%) had PABC. Patients with PABC were younger and tended to have triple-negative BC (TNBC) subtype than non-PABC patients. The 1640 matched non-PABC patients showed a significantly worse mean survival rate than the unmatched non-PABC patients. Patients with PABC had a significantly worse OS and BCSS than those with non-PABC. In multivariate analyses, patients with PABC of luminal B (Ki-67 ≥14.0%) and TNBC subtypes had worse OS and BCSS than patients with non-PABC. Patients with PABC had poorer prognosis than non-PABC patients after adjusting for several prognostic factors. This difference was particularly significant in patients with the luminal B and TNBC subtypes.

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.

CDDO, a PPAR-γ ligand, inhibits TPA-induced cell migration and invasion through a PPAR-γ-independent mechanism.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) acts as a key factor in breast cancer metastasis. Notably, PPAR-γ can inhibit metalloproteinase (MMP), which is involved in cancer metastasis. Our previous study revealed that PPAR-γ was related to breast cancer metastasis. The present study aimed to investigate whether the PPAR-γ ligand 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) mediated suppression of cell invasion and reduced the expression of MMP-9 in breast cancer cells. The results indicated that CDDO reduced MMP-9 expression, cell migration and invasion of breast cancer cells by inhibiting TPA-induced phosphorylation of mitogen-activated protein kinases, and downregulating the activities of activator protein-1 and nuclear factor κB. Notably, knock-out of PPAR-γ by small interfering RNA in MCF-7 cells revealed that TPA-induced MMP-9 expression occurred through a PPAR-γ-independent pathway. These data indicated that the downregulatory effect of CDDO on MMP-9 expression was affected by a mechanism independent of PPAR-γ. In conclusion, the findings of the present study suggested that CDDO may act as a key agent in the regulation of breast cancer metastasis, suggesting CDDO as a new targeted therapy for breast cancer.

Association of lipid profile with obesity among breast cancer survivors: a cross-sectional study.

BACKGROUND: The role of lipid metabolism in obesity and cancer manifestations cannot be underestimated, but whether alterations in lipid metabolism can manipulate the vasculature to promote obesity among breast cancer (BC) survivors is yet to be clearly understood. This study quantified plasma lipid and particle sizes using high-throughput proton (1H) nuclear magnetic resonance (NMR) and tested their associations with obesity among breast cancer (BC) survivors. METHODS: A total of 348 (225 premenopausal and 123 postmenopausal) BC survivors enrolled from five hospitals in Korea were included. We assessed thirty-four plasma lipid biomarkers using 1H NMR, and obesity status was defined as a body mass index (BMI) of 25 kg/m2 or greater. Generalized linear and logistic regression models were applied to estimate the least-square means of BMI (kg/m2) and odds ratio (OR)s of obesity, respectively, and the corresponding 95% confidence interval (CI)s across plasma lipid levels. RESULTS: Mean (SD) values of BMI was 23.3 (3.2) kg/m2 and 90 (25.9%) had BMI of ≥ 25 kg/m2. BMI levels increased with increasing total triglycerides (TG), TG in lipoproteins and very-low-density lipoprotein (VLDL) subfractions. However, BMI levels decreased with increasing tertiles of high-density lipoprotein (HDL)-cholesterol (C) and HDL particle size (HDL-p). Similar associations were observed in the logistic regression models. The increasing and decreasing BMI trends with TG and HDL profiles respectively were predominantly limited to premenopausal BC survivors. CONCLUSIONS: Increasing levels of plasma total TG and TG in lipoproteins were associated with increasing levels of BMI among premenopausal BC survivors. High HDL-C levels and large HDL-p were inversely associated with obesity among premenopausal BC survivors. Due to the cross-sectional design of this study, longitudinal studies are necessary to examine the association between obesity and lipid profile among BC survivors.

The Risk Factors, Incidence and Prognosis of Postpartum Breast Cancer: A Nationwide Study by the SMARTSHIP Group.

The term 'pregnancy-associated breast cancer' is no longer used as it has been consistently reported that breast cancer during pregnancy and breast cancer after delivery (postpartum breast cancer) have different characteristics and prognosis. The purpose of this study is to define postpartum breast cancer by analyzing the incidence rate, related factors, and prognosis according to the timing of breast cancer. Data from the Korean National Health Insurance Service were used to analyze 1,292,727 women aged 20-49 years who birthed their first child between 2007 and 2012. The annual incidence rate of breast cancer after delivery increased every year (7.7 per 10,000 person-years after 5 years, 19.36 per 10,000 person-years after 10 years). The risk of breast cancer was significantly higher (hazard ratio 1.15, 95% CI 1.05-1.27, P=0.0037) in women diagnosed with gestational diabetes, but that was not associated with overall survival (OS). Patients diagnosed with breast cancer within 5 years of delivery had a poorer prognosis than those diagnosed later (5-year OS, <5 years: 91.1% vs. 5-10 years: 96.0%). In multivariate analysis of OS, the hazard ratio of patients diagnosed within 5 years after delivery was twice as high as of patients diagnosed between 5 and 10 years. Women diagnosed with gestational diabetes had an increased risk of breast cancer. Breast cancer patients diagnosed within 5 years of delivery had a poorer prognosis than those diagnosed later. In this regard, careful screening for early diagnosis of high-risk patients and intensive research on new treatment strategies are needed.

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.

Inhibition of cell invasion and migration by targeting matrix metalloproteinase-9 expression via sirtuin 6 silencing in human breast cancer cells.

Sirtuin 6 (SIRT6) regulation is involved in carcinogenesis. However, its role in breast cancer (BC) metastasis remains unclear. We investigated the effects of SIRT6 on protein kinase C activator- and cytokine-mediated cancer cell invasion and migration in MCF-7 and MDA-MB-231 cells and the association between SIRT6 and matrix metalloproteinase-9 (MMP-9) expression. To assess MMP-9 and SIRT6 expression in patients, protein levels in BC tissues were analyzed. MCF-7 and MDA-MB-231 cell viability was analyzed using MTT assays. SIRT6 was silenced in both cell lines and protein secretion, expression, and mRNA levels were analyzed. Transcription factor DNA activity was investigated using luciferase assays. Matrigel invasion assays were used to assess the effects of SIRT6 in both cell lines. SIRT6 and MMP-9 expression in cancer tissues was significantly higher than in paired normal breast tissues. 12-O-tetradecanoylphorbol-13-acetate (TPA) or tumor necrosis factor-α (TNF-α) increased MMP-9 expression and cell invasion and migration, but SIRT6 knockdown abolished these effects. SIRT6 overexpression additively increased TPA- and TNF-α-induced MMP-9 expression. SIRT6 knockdown suppressed the mitogen-activated protein kinase (MAPK) signaling pathway and thus TPA- and TNF-α-induced MMP-9 expression. SIRT6 silencing suppressed TPA- and TNF-α-induced nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) expressions in both cell lines, and treatment with MAPK, NF-κB, and AP-1 inhibitors reduced MMP-9 expression. The anti-invasive effects of SIRT6 in BC cells might be mediated by suppression of MAPK phosphorylation and reduction in NF-κB and AP-1 DNA activities, leading to MMP-9 downregulation, suggesting that SIRT6 modulation has the potential to target BC metastasis.

Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.

BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041). CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.

Comprehensive clinical characterization of patients with BRCA1: c.5017_5019del germline variant.

Purpose: We provide evidence for the reclassification of the BRCA1:c.5017_5019del variant by presenting the clinicopathological characteristics, clinical outcomes, and family history of breast or ovarian cancer in 17 patients with this variant. Methods: This study included breast or ovarian cancer patients tested for BRCA1/2 genes between January 2008 and June 2020 at 10 medical centers in Korea. We retrospectively reviewed 17 probands from 15 families who had the BRCA1:c.5017_5019del variant according to the electronic medical records. Results: We present 10 breast cancer patients and 7 ovarian cancer patients from 15 families identified as having BRCA1:c.5017_5019del and a total of 19 cases of breast cancer and 14 cases of ovarian cancer in these families. The ratio of breast-to-ovarian cancer was 1.3:1. Breast cancer patients with this variant showed a rich family history of breast or ovarian cancer, 8 patients (80.0%). The mean age at diagnosis was 45.4 years and 6 patients (60.0%) were categorized into hormone-receptor-negative breast cancer. Also, the ovarian cancer patients with this variant showed strong family histories of breast and/or ovarian cancer in 4 patients (57.1%). Conclusion: We presented clinical evidence for the reclassification of BRCA1:c.5017_5019del as a likely pathogenic variant (LPV). Reclassification as LPV could result in the prophylactic treatment and medical surveillance of probands, family testing recommendations, and appropriate genetic counseling of their families.