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.

Prognostic factors after isolated ipsilateral local and regional recurrence in HER2-negative luminal breast cancer: a multi-center retrospective study.

BACKGROUND: Although the incidence of isolated ipsilateral local and regional recurrence (IILRR) in human epidermal growth factor 2 (HER2)-negative luminal breast cancer is low, it is important because of its potential risk of distant metastasis and breast cancer related mortality. The aim of this study was to investigate prognostic factor and survival of IILRR using a large multi-center cohort. METHODS: Data on patients with HER2-negative luminal breast cancer between 2005 and 2015 were retrieved. The endpoint was IILRR rate, post-recurrence progression-free survival (P-PFS), and post-recurrence overall survival (P-OS). Prognostic factors for progression and overall survival (OS) after IILRR were assessed by multivariate analysis. RESULTS: Eighty (2.37%) patients experienced IILRR. Of them, 27 (33.7%) experienced a disease progression, including 23 (85.2%) who had distant metastasis. The median DFS was 48.5 months (range, 4-138 months). In 72.5% of cases, the first IILRR occurred after 3 years. Estimated 5-year P-PFS rates were 86.2%, 69.7%, 69.0%, 42.7%, and 82.2% for patients with age < 40 at diagnosis (p = 0.015), T1 stage (p = 0.012), stage I (p < 0.001), lymphovascular invasion (p = 0.003), and patients with post-recurrence endocrine therapy (p < 0.001), respectively. The 5-year Kaplan-Meier P-OS rate for patients was 81.4%. Post-recurrence endocrine therapy was independent factor for progression (HR: 0.176, p < 0.001) and OS (HR: 0.080, p < 0.001). CONCLUSIONS: Although there is no standardized treatment for IILRR yet, endocrine therapy after local resection plays a more important role in improving prognosis than chemotherapy or radiotherapy in HER2-negative luminal breast cancer.

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.

A nomogram constructed using intraoperative ex vivo shear-wave elastography precisely predicts metastasis of sentinel lymph nodes in breast cancer.

OBJECTIVE: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. RESULTS: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. CONCLUSIONS: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. KEY POINTS: • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.

A phase II study investigating the acute toxicity of targeted intraoperative radiotherapy as tumor-bed boost plus whole breast irradiation after breast-conserving surgery in Korean patients.

BACKGROUND: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer. METHODS: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991). RESULTS: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications. CONCLUSIONS: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: a retrospective analysis.

PURPOSE: Neoadjuvant chemotherapy (NAC) is being increasingly used to treat locally advanced breast cancer and to conserve the breast. In triple-negative breast cancer and HER2-positive breast cancer, a high density of tumor-infiltrating lymphocytes (TILs) is an important predictor of NAC response. Thus far, it remains unclear whether the TIL scores in core needle biopsies (CNBs) are closely representative of those in the whole tumor section in resected specimens. This study aimed to evaluate the concordance between the TIL scores of CNBs and resected specimens of breast cancer. METHODS: A total of 220 matched pairs of CNBs and resected specimens of breast cancer were included. Stromal TILs were scored on slides stained with hematoxylin and eosin. Clinicopathologic parameters and the agreement of the TIL scores between CNBs and resected specimens were statistically analyzed. RESULTS: The average TIL score was approximately 4.4% higher for the resected specimens than for the CNBs. When the tumors were divided into two groups according to a 60% TIL score cut-off (low and intermediate TIL vs. high TIL), 8.2% showed discordance between the CNB and resected specimen. The overall intraclass correlation coefficient (ICC) value of the TIL score was 0.895 (95% confidence interval, 0.864-0.920, P < 0.001), and all molecular subtypes showed ICC values over 0.8 (P < 0.001). The ICC values were > 0.9 when ≥ 5 cores were included in the CNBs. Tumors with discordant TILs were characterized by histologic grade III, ER negativity, high proliferative index, and HER2 and triple-negative subtypes. A high proliferative index was an independent risk factor for TIL discordance. CONCLUSIONS: The TIL score in CNB specimens is a reliable value that reflects the TIL status of the entire tumor in resected specimens of breast cancer. More than five CNB cores may accurately predict the TIL score of the entire tumor.

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.

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.

Marked Reduction in the Risk of Dementia in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: An inverse relationship between cancer and neurodegenerative disease, which presents the possibility of a reduced risk of dementia in cancer patients, has been suggested previously. However, a nationwide longitudinal population-based study of specific types of cancer with due consideration of treatment effects has not been conducted. Materials and Methods: This nationwide population-based cohort study used data obtained in a 12-year period (January 2007- December 2018) in the Korean National Health Insurance claims database. All female breast cancer patients (age ≥ 50 years) diagnosed between 2009 and 2010 were included after excluding those with physician visits for any cancer during a 2-year period (2007-2008). Patients with senile cataract constituted the control group. The main study outcome was the risk of developing dementia. RESULTS: From a total of 90,396 and 85,906 patients with breast cancer and cataract, respectively, patients without behavior codes were excluded. Data for 15,407 breast cancer patients and 7,020 controls were analyzed before matching. After matching for comorbidities and age, either group comprised 2,252 patients. The median follow-up time was 104.1±24.0 months after matching. After matching, breast cancer was a predictor of a lower risk of for dementia (hazard ratio, 0.091; 95% confidence interval, 0.075 to 0.111; p < 0.001). In breast cancer patients, receiving chemotherapy and endocrine therapy did not significantly affect the incidence of dementia. CONCLUSION: Breast cancer was associated with a remarkably decreased risk of dementia. The findings strongly suggest an inverse relationship between cancer and neurodegeneration, regardless of the adverse effects of cancer treatment on cognitive function.

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.

Pylorus- and spleen-preserving total pancreatoduodenectomy with resection of both whole splenic vessels: feasibility and laparoscopic application to intraductal papillary mucin-producing tumors of the pancreas.

BACKGROUND: Total pancreatectomy is recommended for intraductal papillary mucinous tumors with widespread involvement of the entire pancreas. Organ-preserving and minimally invasive surgery should be applied in benign and borderline pancreatic lesions. METHODS: Pylorus- and spleen-preserving total pancreatoduodenectomy (PpSpTPD) with segmental resection of both splenic vessels was attempted for five patients. The technique was based on the concepts of two surgical procedures: pylorus-preserving pancreatoduodenectomy and distal pancreatectomy with segmental resection of splenic vessels ("extended" Warshaw's procedure). RESULTS: Three patients underwent laparoscopic-assisted PpSpTPD and two underwent open surgery. No mortality was noted. Short-term follow-up (median, 28 months) suggested that all patients tolerated the insulin therapy and showed relatively good nutritional status. Only minimal to moderate perigastric fundal varices were noted without gastrointestinal bleeding. CONCLUSIONS: PpSpTPD with segmental resection of both splenic vessels is feasible and safe. Even a minimally invasive approach can be indicated in selected patients.

Avoiding unnecessary intraoperative sentinel lymph node frozen section biopsy of patients with early breast cancer.

Purpose: After the publication of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial, the rate of axillary lymph node dissection has reduced. Thus, the need for intraoperative frozen section biopsy of sentinel lymph nodes (SLNs) has become controversial. We identified patients for whom intraoperative SLN frozen section biopsy could be omitted and found that frozen section biopsy rate can be reduced. Methods: We reviewed the records of patients with tumors ≤5 cm in diameter who underwent breast-conserving surgery between January 2013 and December 2019 at Seoul St. Mary's Hospital. Clinicopathological and imaging characteristics were compared according to number of positive SLNs (0-2 SLNs positive vs. ≥3 SLNs positive). Results: A total of 1,983 patients were included in this study. Thirty-two patients (1.6%) had at least 3 positive SLNs. Patients with ≥3 positive SLNs had significantly larger tumors and were more frequently high-grade tumors (P < 0.001 and P = 0.002, respectively). Identification of suspicious lymph nodes on imaging studies was also associated with the presence of ≥3 positive SLNs (hazard ratio, 11.54; 95% confidence interval, 4.42-30.10). All patients with none or only 1 suspicious lymph node on any imaging modality (n = 647, 32.6%) had 0-2 positive SLNs. Also, among patients with clinical T1-stage tumors and at least 2 suspicious lymph nodes on only 1 imaging modality (n = 514, 25.9%), only 2 cases had ≥3 positive SLNs. Conclusion: We found that intraoperative SLN frozen biopsy could be omitted in patients using tumor size and axillary lymph node status on imaging modality.

The Radiological Response Rate Pattern Is Associated With Recurrence Free Survival in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

PURPOSE: The aim of this study was to evaluate the radiological response rate patterns during neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Patients who underwent NAC with two specific chemotherapy regimens (doxorubicin with cyclophosphamide or doxorubicin with docetaxel) and who underwent a response evaluation every two cycles were included in the study. The initial response ratio was defined as the ratio of the largest tumor diameter at diagnosis to that after two cycles of NAC. The latter response ratio was defined as the ratio between the tumor size after two cycles and that after four cycles of NAC. The radiological response rate pattern was divided into three groups: the fast-to-slow response group (F-S group, initial response ratio > latter response ratio + 20%), slow-to-fast response group (S-F group, latter response ratio > initial response ratio + 20%), and constant response group (less than 20% difference between the initial and latter response ratios). RESULTS: In total, 177 patients were included in the analysis. Forty-two (23.9%) patients were categorized into the F-S group, 26 (14.8%) into the S-F group, and 108 (61.2%) into the constant group. Clinicopathologic factors did not differ according to radiologic response rate patterns. The median follow-up period was 50 months (range, 3-112) months. In the univariate analysis, the F-S group had a significantly worse recurrence-free survival than the S-F and constant groups (hazard ratio [HR], 3.63; 95% confidence interval [CI], 1.05-12.46; p = 0.041). The F-S group also presented with significantly worse survival than the S-F group in the multivariate analysis (HR, 3.45; 95% CI, 1.00-11.89; p = 0.049). CONCLUSION: The F-S group had a poorer survival rate than the S-F group. Radiological response rate patterns may be useful for accurate prognostic assessments, especially when considering post-neoadjuvant therapy.

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.

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.

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.

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.