Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy.

INTRODUCTION: The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST. METHODS: This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model. RESULTS: Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%). CONCLUSIONS: SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.

Relationship between tamoxifen and cataracts: a nationwide cohort study of women in South Korea.

PURPOSE: Although prospective randomized clinical trials have reported that the use of prophylactic tamoxifen in patients at a high risk of breast cancer is associated with an increased risk of cataracts development, such findings are inconsistent. This study aimed to clarify the relationship between adjuvant tamoxifen use and cataracts risk using a nationwide longitudinal population-based registry. METHODS: This retrospective cohort study was conducted using the Korean National Health Insurance claims database over a 15-year period (January 2007-December 2021). Data from all female patients diagnosed with ductal carcinoma in situ (DCIS) between 2009 and 2015 were extracted. We evaluated the incidence of cataracts diagnosis and surgery after adjuvant tamoxifen administration in patients with DCIS. RESULTS: A total of 43,434 patients who met the inclusion criteria were diagnosed with DCIS between 2009 and 2015. Data from 2849 patients receiving tamoxifen and 1615 patients not receiving tamoxifen were analyzed before matching. After matching for comorbidities, type of breast surgery, and age, both groups consisted of 1597 patients. Both before and after matching, adjuvant tamoxifen was not a significant factor for an increased risk of cataracts diagnosis alone or with surgery. CONCLUSION: Our study showed that adjuvant tamoxifen was not a risk factor for increased cataracts diagnosis and surgery in patients with DCIS. This finding provides a basis for physicians to reduce their ocular toxicity concerns regarding the risk of patients developing cataracts by tamoxifen treatment.

A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. METHODS: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. DISCUSSION: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

RT-induced dynamic changes in the lymphocyte-to-monocyte ratio in patients with breast cancer indicate poor prognosis.

PURPOSE: Radiation-induced anti-tumor responses occur in the immune system, particularly in peripheral blood mononuclear cells (PBMCs), which are overly sensitive to ionizing radiation. Irradiation of PBMCs is associated with inflammation. We assessed the association between radiotherapy (RT)-induced changes in peripheral blood cells, utilizing the lymphocyte-to-monocyte ratio (LMR), and survival outcome in breast cancer patients who underwent breast-conserving surgery followed by adjuvant RT. METHODS: LMR values were obtained from retrospective data, and serial sampling of blood before the first and last RT sessions was performed. The cut-off point was analyzed using the Youden index and receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were the main outcomes. RESULTS: Patients with RT-induced low LMR had significantly shorter RFS (hazard ratio [HR] 2.730; 95% confidence interval [CI], 1.607-4.636, P = 0.0002) and OS (HR 2.890; 95% CI 1.410-5.924, P = 0.0038). The results were more robust in the subgroup of patients who received chemotherapy. Multivariate analysis showed that lymph node metastasis and RT-induced low LMR were associated with poor RFS (HR 1.763; 95% CI, 1.017-3.059, P = 0.044) and OS (HR 2.254; 95% CI, 1.060-4.796, P = 0.035). CONCLUSION: This study demonstrates that RT-induced low LMR is a valid prognostic marker for recurrence and survival in breast cancer patients undergoing RT.

Axillary response according to neoadjuvant single or dual human epidermal growth factor receptor 2 (HER2) blockade in clinically node-positive, HER2-positive breast cancer.

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy.

Body mass index and absolute lymphocyte count predict disease-free survival in Korean breast cancer patients.

BACKGROUND: Our study evaluated the association between body mass index (BMI) and absolute lymphocyte count (ALC) in breast cancer patients and healthy females. Additionally, we determined the prognostic value of these factors in breast cancer. METHODS: We retrospectively identified 1225 primary invasive breast cancer patients and 35,991 healthy females. Factors including BMI and complete blood count associated with disease-free survival (DFS) were assessed using a multi-variable Cox proportional hazard model. RESULTS: BMI and ALC were positively correlated in breast cancer patients and healthy females (both P < 0.001). In multi-variable analysis, overweight or obese participants had worse DFS (hazards ratio [HR], 1.98; 95% confidence interval [CI], 1.34-2.92; P = 0.001) than underweight or normal-weight individuals, but patients with high ALC had better DFS than those with low ALC (HR, 0.43; 95% CI, 0.29-0.65; P < 0.001). After risk stratification according to BMI/ALC, high-risk patients with high BMI/low ALC had worse DFS than others (HR, 2.48; 95% CI, 1.70-3.62; P < 0.001). CONCLUSIONS: BMI and ALC were positive correlated, but their effect on breast cancer prognosis was opposite. Patients with high BMI/low ALC had worse DFS than others. Underlying mechanisms for effect of BMI/ALC on breast cancer prognosis should be studied in the future.

Diagnostic Accuracy of Nonmass Enhancement at Breast MRI in Predicting Tumor Involvement of the Nipple: A Prospective Study in a Single Institution.

Background Although nonmass enhancement (NME) extension to the nipple at preoperative MRI frequently leads to sacrifice of the nipple-areolar complex (NAC), its correlation with pathologically confirmed NAC involvement is unclear. Purpose To evaluate the diagnostic accuracy of using NME extension to the subareolar region at breast MRI to predict pathologic nipple involvement and the eligibility for nipple-sparing mastectomy. Materials and Methods From November 2017 to November 2019, the authors prospectively enrolled participants with breast cancer and NME within 2 cm of the nipple at breast MRI who underwent surgery that included removal of the NAC. The authors evaluated NME extensions that were ipsilateral and contiguous with the biopsy-proven tumor lesions on images acquired during the early contrast phases. Pathologic nipple involvement and the distance from the nipple to the nearest cancer cell were evaluated by using serial vertical sectioning of the area extending from the entire NAC to the tumor. The primary end point was the positive predictive value (PPV) of NME, which was calculated as follows: (number with pathologic nipple invasion and NME extension to the nipple at breast MRI/number with NME extension to the nipple at breast MRI) × 100. Results Of 64 women (mean age, 52 years ± 9.8 [standard deviation]), 49 (77%) had NME extension to the nipple at breast MRI. The PPV of NME extension to the nipple was 86% (42 of 49 women; 95% CI: 73, 94). Among the 15 participants without NME extension to the nipple, only one (7%) had pathologic nipple involvement. The diagnostic accuracy of using NME extension to the nipple was 88% (56 of 64 women; 95% CI: 77, 95). The radiologic distance correlated well with the pathologic distance (Spearman correlation coefficient = 0.71, P = .003). Conclusion Nonmass enhancement extension to the nipple base at preoperative MRI has a high positive predictive value for identifying tumor involvement of the nipple, a contraindication to nipple-sparing mastectomy. © RSNA, 2021 Online supplemental material is available for this article.

Comparison of resection margin status after single or double radiopaque marker insertion for tumor localization in breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: Insertion of radiopaque markers is helpful for tumor localization in patients receiving neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS). The aim of this retrospective study was to investigate the pathologic margin status in patients with single or double marker insertion. METHODS: We reviewed the records of 130 patients with marker insertion prior to NAC followed by BCS from January 2016 to September 2019. Under ultrasonography guidance, single or double markers were inserted to localize a tumor in the breast. The incidence of additional resection after frozen biopsy and re-excision after permanent pathologic diagnosis was analyzed. RESULTS: In a total of 130 patients, 104 had a single marker in the center of the tumor and 26 had double markers at the periphery of the tumor before NAC. Among 69 patients with residual invasive tumors after NAC, there was no difference in the additional resection rate after frozen biopsy (single vs. double markers; 14.3% vs. 38.5%, P = .059) or the re-excision rate after final pathologic diagnosis (0% vs. 7.7%, P = .188). After propensity score matching for tumor size and subtypes, the two groups showed no differences in the additional resection rate after frozen biopsy (7.7% vs. 19.2%, P = .139) or the re-excision rate (0% vs. 3.8%, P = .308). After a median follow-up of 19 months (range 8-48 months), local recurrence-free survival did not differ between the two groups (log-rank P = .456). CONCLUSIONS: Number of inserted markers for tumor localization did not affect the pathologic margin status after BCS.

Risk of Secondary Cancer after Adjuvant Tamoxifen Treatment for Ductal Carcinoma In Situ: A Nationwide Cohort Study in South Korea.

Endocrine therapy is the mainstay treatment for hormone receptor-positive ductal carcinoma in situ. The aim of this study was to examine the long-term secondary malignancy risk of tamoxifen therapy. The data of patients diagnosed with breast cancer between January 2007 and December 2015 were retrieved from the database of the Health Insurance Review and Assessment Service of South Korea. The International Classification of Diseases, 10th revision, was used to track all-site cancers. Age at the time of surgery, chronic disease status, and type of surgery were considered covariates in the propensity score matching analysis. The median follow-up duration was 89 months. Forty-one patients in the tamoxifen group and nine in the control group developed endometrial cancer. The Cox regression hazard ratio model showed that tamoxifen therapy was the only significant predictor of the development of endometrial cancer (hazard ratio, 2.791; 95% confidence interval, 1.355-5.747; p = 0.0054). No other type of cancer was associated with long-term tamoxifen use. In consonance with the established knowledge, the real-world data in this study demonstrated that tamoxifen therapy is related to an increased incidence of endometrial cancer.

Association between tamoxifen and incidence of osteoporosis in Korean patients with ductal carcinoma in situ.

Introduction: The partial estrogen-agonist action of tamoxifen on bone receptors has beneficial effects on bone mineral density. However, in premenopausal women, the use of tamoxifen causes systemic estrogen depletion, which has detrimental effects on bone health. We aim to investigate the association between tamoxifen and osteoporosis in the real world using data from a longitudinal nationwide cohort of Korean patients. Methods: Data were collected from the National Health Insurance claims database in South Korea. Osteoporosis was defined by diagnostic codes accompanying prescription data for osteoporosis. The cumulative incidence was analyzed by Kaplan-Meier survival curves and the risk factors were analyzed using a multivariable Cox proportional hazard regression model. Results: Between 2009 and 2015, of the 4,654 women with ductal carcinoma in situ (DCIS) without prior osteoporosis, 2,970 were prescribed tamoxifen and 1,684 were not. A total of 356 DCIS survivors were later diagnosed with osteoporosis during a median follow-up period of 84 months. In the overall population, tamoxifen was associated with a low risk of osteoporosis, before and after propensity matching adjusted for age, operation type, and comorbidities (before matching, hazard ratio [HR]=0.69, 95% confidence interval [CI]=0.559-0.851, p<0.001; after matching, HR=0.664, 95% CI=0.513-0.858, p=0.002). In the subgroup analysis, findings were consistent in postmenopausal women but were not evident in the younger age group. Conclusion: In a nationwide cohort study, a low risk of osteoporosis was associated with the use of tamoxifen. The protective effect of tamoxifen was more profound in older women and was not related to the incidence of osteoporosis in younger women.

Prediction of Cardiac Toxicity by Measurement of Coronary Artery Calcium Scoring Method Using Chest Computed Tomography in Early Breast Cancer Patients Treated with Trastuzumab.

Background: In human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer, prediction of trastuzumab-related cardiac toxicity remains a challenge. The coronary calcium artery (CAC) reflects the total coronary plaque burden, which predicts the risk of atherosclerosis. We investigated the prediction of left ventricular ejection fraction (LVEF) decline in breast cancer according to CAC scores. Methods: A total of 347 patients were enrolled from Seoul St Mary's Hospital between January 2010 and December 2019. Chest computed tomography (CT) was performed at a single tertiary center. Patients who received trastuzumab for HER2-positive early breast cancer were included in this study. Results: Of the 347 patients, 312 and 35 had CAC scores of 0 and ≥1, respectively. The CAC ≥1 group was associated with older age, body mass index, and receipt of left breast irradiation. The CAC ≥1 group was significantly associated with LVEF decline (absolute value, ≤50%) (hazard ratio [HR] 12.038, 95% confidence interval [CI] 2.845-50.937, p = 0.001), LVEF decline (absolute value, ≤55%) (HR 4.439, 95% CI: 1.787-11.028, p = 0.001), and decline in LVEF of ≥10% points compared with baseline echography (HR 5.083, 95% CI: 1.658-15.582, p = 0.004). Even after adjusting for other clinical factors, CAC ≥1 remained a significant predictor of decreased LVEF. Conclusion: Our findings suggest that the CAC score is a significant predictor of cardiac toxicity following trastuzumab treatment in HER2-positive breast cancer. Therefore, CAC measurement could reduce cardiac toxicity by distinguishing patients at high risk for trastuzumab.

Prognostic impact of radiotherapy-induced-lymphopenia in patients treated with breast-conservative surgery.

We investigated a prognostic impact of radiotherapy-induced lymphopenia (RIL) in breast cancer patients treated with breast-conservative surgery (BCS). We included 531 breast cancer patients who were treated with BCS and adjuvant radiotherapy. None of these received (neo)adjuvant chemotherapy. Pre- and post- absolute lymphocyte counts (ALC) were reviewed before and after radiotherapy. The primary endpoint was to evaluate recurrence-free survival (RFS) according to the pre-to-post ALC ratio. Binary logistic regression model was used to identify risk factors for RIL. Either continuous or categorical (> 2.4) pre-to-post ALC ratio was associated with RFS. In 531 patients receiving whole breast irradiation (WBI) and regional nodal irradiation (RNI), RFS was significantly reduced in the patients with high pre-to-post ALC ration (> 2.4). In multivariable analysis, low pre-to-post post ALC ratio was significantly related to decreased RFS in the multivariable analysis (HR 2.293, 95% CIs 1.110-4.735, P = 0.025). In 452 patients treated with WBI alone, high pre-to-post ALC ratio was still significantly associated with decreased RFS in the multivariable analysis (HR 2.708, 95% CIs 1.016-7.218, P = 0.046). In binary logistic regression analysis, RNI was only significant risk factor for clinically meaningful RIL. Our findings show that a markedly decrease in ALC during radiotherapy has a negative prognostic impact.

Risk of developing depression from endocrine treatment: A nationwide cohort study of women administered treatment for breast cancer in South Korea.

Background: Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression. Methods: This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group. Results: The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression (p=0.7295 and p=0.2668, respectively), nor was it a significant factor for an increased risk for suicide attempt (p=0.6381 and p=0.8366, respectively). Conclusions: Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Early Standardized Uptake Value Reduction in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: We investigated the treatment response and prognosis using the neutrophil-to-lymphocyte ratio (NLR) and standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in neoadjuvant settings. METHODS: Baseline NLR and maximum SUV (SUVmax) were retrospectively analyzed in 273 females with breast cancer who received neoadjuvant chemotherapy followed by surgery. Of these, 101 patients underwent 18F-FDG PET after 3-4 neoadjuvant chemotherapy cycles, which allowed the measurement of ΔSUVmax, an early reduction in SUVmax. NLR and early SUVmax reduction (ΔSUVmax) were classified as low and high, respectively, relative to the median values. RESULTS: The mean NLR was lower, and the mean ΔSUVmax was higher in patients with pathologic complete response (pCR) than in those with residual tumors. The ΔSUVmax was an independent variable associated with pCR. Furthermore, the high NLR group had poor recurrence-free survival (RFS) and overall survival. Among patients with ΔSUVmax data, high NLR (adjusted hazard ratio, 2.82; 95% confidence intervals [CI], 1.26-6.28; P = 0.016) and low ΔSUVmax (adjusted hazard ratio, 2.39; 95% CI, 1.07-5.34; P = 0.037) were independent prognostic factors for poor RFS. The categorization of the patients into four groups according to the combination of NLR and ΔSUVmax showed that patients with high NLR and low ΔSUVmax had significantly poorer RFS. CONCLUSION: Baseline NLR and ΔSUVmax were significantly associated with the prognosis of patients with breast cancer who received neoadjuvant chemotherapy. These results suggest that metabolic non-responders with defective immune systems have worse survival outcomes.

Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR.

We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.

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.

Residual Tumor Patterns of Breast Cancer on MRI after Neo-Adjuvant Chemotherapy: Impact on Clinicopathologic Factors and Prognosis.

(1) Background: Residual breast cancer after neoadjuvant chemotherapy (NAC) could have a variable image pattern on a follow-up breast magnetic resonance image (MRI). In this study, we compared the clinical outcome of breast cancer patients with different residual tumor patterns (RTP) on a breast MRI after NAC. (2) Methods: A total of 91 patients with breast cancer who received NAC and subsequent curative surgery were selected. All included patient had residual breast cancer after NAC and showed a partial response on a breast MRI. Pre- and post-treatment were reviewed by an experienced radiologist to evaluate different RTP, and classified into two groups: concentric and scattered patterns. The clinicopathologic parameters and survival outcomes [recurrence-free survival (RFS) and distant metastasis-free survival (DMFS)] were analyzed according to different RTP. (3) Results: Patients with a scattered pattern had a larger extent of pre-treated non-mass enhancement and more frequently received total mastectomy. With a median follow-up period of 37 months, RTP were not significantly associated with RFS or DMFS. (4) Conclusions: In the patients with residual breast cancer after NAC, RTP on an MRI had no effect on the patients' clinical outcome. The curative resection of the tumor bed and securing the negative resection margins appear to be important in the treatment of patients with residual breast cancer after NAC.

18F-FDG uptake of visceral adipose tissue on preoperative PET/CT as a predictive marker for breast cancer recurrence.

Glucose utilization by visceral adipose tissue (VAT) reflects inflammatory activity, which also promotes tumor growth and carcinogenesis. The effect of metabolically active VAT on survival outcomes in breast cancer is unknown. We investigated survival outcomes in patients with breast cancer based on the standardized uptake value (SUV) of VAT (SUVmean-VAT) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). A total of 148 patients with breast cancer were divided into high- and low groups according to their SUVmean-VAT and SUVmax-tumor. Clinical characteristics and survival outcomes were compared between the groups. High SUVmean-VAT was associated with poor recurrence-free survival (RFS; hazard ratio [HR], 2.754; 95% confidence interval [CI], 1.090-6.958, p = 0.032) and distant metastasis-free survival (DMFS; HR, 3.500; 95% CI, 1.224-10.01, p = 0.019). Multivariate analysis showed that high SUVmean-VAT was a significant factor for poor RFS and poor DMFS (p = 0.023 and 0.039, respectively). High SUVmax-tumor was significantly associated with short RFS (p = 0.0388). Tumors with a high SUV tended to have a short DMFS, although the difference was not significant (p = 0.0718). Our findings showed that upregulated glucose metabolism in the VAT measured using 18F-FDG PET/CT may be a prognostic biomarker for adverse outcomes in breast cancer.

Application of the 21-Gene Recurrence Score in Patients with Early HR-Positive/HER2-Negative Breast Cancer: Chemotherapy and Survival Rate According to Clinical Risk.

We assessed the impact of 21-gene Recurrence Score (RS) assay on chemotherapy decision-making according to binary clinical risk stratification in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. We included patients with tumors measuring 1-5 cm, N0-1, and HR+/HER2- breast cancer who underwent surgery followed by adjuvant treatment. The clinical risk was determined by a modified version of Adjuvant! Online. We performed propensity score matching (PSM) according to the application of 21-gene RS separately in the low and high clinical risk groups. Before PSM, 342 (39.0%) of 878 patients were classified as having high clinical risk. In the high clinical risk group, 21-gene RS showed a significantly reduced chemotherapy rate of 39.3%, without increasing the recurrence. After PSM, the 21-gene RS application significantly reduced chemotherapy rate by 34.0% in 200 patients with high clinical risk (21-gene RS application, 32.0% vs. no 21-gene RS application, 66.0%, p < 0.001). There was also no significant difference in RFS according to 21-gene RS status in the high clinical risk group (log-rank test, p = 0.467). These results support the usefulness of the 21-gene RS to reduce the chemotherapy rate without adversely affecting prognosis in a high clinical risk group.

Relationship of the standard uptake value of 18F-FDG-PET-CT with tumor-infiltrating lymphocytes in breast tumors measuring ≥ 1 cm.

Evidence suggests that tumor cells and tumor-infiltrating lymphocytes (TILs) compete for glucose in the tumor microenvironment and that tumor metabolic parameters correlate with localized immune markers in several solid tumors. We investigated the relationship of the standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET-CT) with stromal TIL levels in breast cancer. We included 202 patients who underwent preoperative 18F-FDG-PET-CT and had a tumor measuring ≥ 1 cm. Maximum SUV (SUVmax) was determined using 18F-FDG-PET-CT. Multiple logistic regression was used to identify factors related to high TIL levels (≥ 40%). All tumors were treatment naïve. A significant and weak correlation existed between continuous SUVmax and continuous TIL levels (p = 0.002, R = 0.215). Tumors with high SUVmax (≥ 4) had higher mean TIL levels than those with low SUVmax (< 4). In multivariable analysis, continuous SUVmax was an independent factor associated with high TIL levels; each 1-unit increment in SUVmax corresponded to an odds ratio of 1.14 (95% confidence interval: 1.01-1.29) for high TIL levels. Our study implies that SUV is associated with TILs in breast cancer and provides clinical evidence that elevated glucose uptake by breast tumors can predict the immune system-activated tumor micromilieu.