Radiation dose estimation with multiple artificial neural networks in dicentric chromosome assay.

PURPOSE: The dicentric chromosome assay (DCA), often referred to as the 'gold standard' in radiation dose estimation, exhibits significant challenges as a consequence of its labor-intensive nature and dependency on expert knowledge. Existing automated technologies face limitations in accurately identifying dicentric chromosomes (DCs), resulting in decreased precision for radiation dose estimation. Furthermore, in the process of identifying DCs through automatic or semi-automatic methods, the resulting distribution could demonstrate under-dispersion or over-dispersion, which results in significant deviations from the Poisson distribution. In response to these issues, we developed an algorithm that employs deep learning to automatically identify chromosomes and perform fully automatic and accurate estimation of diverse radiation doses, adhering to a Poisson distribution. MATERIALS AND METHODS: The dataset utilized for the dose estimation algorithm was generated from 30 healthy donors, with samples created across seven doses, ranging from 0 to 4 Gy. The procedure encompasses several steps: extracting images for dose estimation, counting chromosomes, and detecting DC and fragments. To accomplish these tasks, we utilize a diverse array of artificial neural networks (ANNs). The identification of DCs was accomplished using a detection mechanism that integrates both deep learning-based object detection and classification methods. Based on these detection results, dose-response curves were constructed. A dose estimation was carried out by combining a regression-based ANN with the Monte-Carlo method. RESULTS: In the process of extracting images for dose analysis and identifying DCs, an under-dispersion tendency was observed. To rectify the discrepancy, classification ANN was employed to identify the results of DC detection. This approach led to satisfaction of Poisson distribution criteria by 32 out of the initial pool of 35 data points. In the subsequent stage, dose-response curves were constructed using data from 25 donors. Data provided by the remaining five donors served in performing dose estimations, which were subsequently calibrated by incorporating a regression-based ANN. Of the 23 points, 22 fell within their respective confidence intervals at p < .05 (95%), except for those associated with doses at levels below 0.5 Gy, where accurate calculation was obstructed by numerical issues. The accuracy of dose estimation has been improved for all radiation levels, with the exception of 1 Gy. CONCLUSIONS: This study successfully demonstrates a high-precision dose estimation method across a general range up to 4 Gy through fully automated detection of DCs, adhering strictly to Poisson distribution. Incorporating multiple ANNs confirms the ability to perform fully automated radiation dose estimation. This approach is particularly advantageous in scenarios such as large-scale radiological incidents, improving operational efficiency and speeding up procedures while maintaining consistency in assessments. Moreover, it reduces potential human error and enhances the reliability of results.

BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enriched in patients with BRCA1 mutation compared to the wild-type. iCAFs in patients with BRCA1 mutation exhibited outgoing signals to endothelial cells (ECs) clusters, including chemokine (C-X-C motif) ligand (CXCL) and vascular endothelial growth factor (VEGF). During CXCL signaling, the atypical chemokine receptor 1 (ACKR1) mainly interacts with CXCL family members in tumor endothelial cells (TECs). ACKR1-high TECs also showed high expression levels of angiogenesis-related genes, such as ANGPT2, MMP1, and SELE, which might lead to EC migration. Furthermore, iCAFs showed VEGF signals for FLT1 and KDR in TECs, which showed high co-expression with tip cell marker genes, including ZEB1 and MAFF, involved in sprouting angiogenesis. Moreover, BRCA1 mutation patients with relatively abundant iCAFs and tip cell gene expression exhibited a limited response to neoadjuvant chemotherapy, including cisplatin and bevacizumab. Importantly, our study observed the intricate link between iCAFs-mediated angiogenesis and chemoresistance in TNBC with BRCA1 mutation.

Analysis of clinical factors and ultrasound features associated with COVID-19 vaccine-related axillary lymphadenopathy: A large group study.

PURPOSE: To investigate factors that distinguish COVID-19 vaccine-related axillary lymphadenopathy from malignancy or other etiologies. METHODS: From June 2021 to April 2022, 3859 consecutive female patients had breast and axillary ultrasound (US) at our institution. After exclusions, 592 patients were included in the study. We retrospectively reviewed clinical history and US features of enlarged axillary lymph nodes. Assessed clinical factors included age, vaccination type, dose and vaccination date, and ultrasound features included cortical thickness, shape, marginal irregularity, focal cortical thickening, fatty hilum, and number and anatomic location of enlarged lymph nodes. The seven US features were used to score the severity of lymphadenopathy. Binary logistic models and independent two-sample t-tests were used for statistical analysis. RESULTS: Among 592 patients (mean age 49.3 ± 10.3 years), 406(68.6%), 90(15.2%), 42(7.1), 4(0.7%) and 50(8.4%) patients received Pfizer, AstraZeneca, Moderna, Janssen and cross inoculation of more than one type, respectively. 185(31.3%), 376(63.5%) and 31(5.2%) patients received a first, second and third dose, respectively. The interval between vaccination and US was 30.9 ± 21.5 days. US showed axillary lymphadenopathy (LAP) in 113 patients (19.1%). Clinical factors associated with LAP were age younger than 50 years, mRNA vaccine, first dose and shorter interval(P < 0.05). US features associated with LAP were mean cortical thickness of 4.6 ± 1.63 mm, oval shape (70.8%), smooth margin (53.1%), focal cortical thickening (62.8%) and preserved fatty hilum (84.1%). Using our scoring method, the mean overall score for vaccine-related LAP was 2.45 ± 1.51 points. CONCLUSION: Awareness of influencing factors and sonographic features can help differentiate COVID-19 vaccine-related adenopathy from other etiologies.

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.

Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer.

Importance: Both high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)-positive ERBB2-negative (ER+/ERBB-) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known. Objective: To assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB- breast cancer with low RS. Design, Setting, and Participants: This cohort study included women treated for ER+/ERBB2- breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea. Exposures: Recurrence score and Ki-67 level. Main Outcomes and Measures: A Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy. Results: A total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P < .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02). Conclusions and Relevance: In this cohort study of patients with ER+/ERBB2- breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.

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.

Association of Body Mass Index With 21-Gene Recurrence Score Among Women With Estrogen Receptor-Positive, ERBB2-Negative Breast Cancer.

Importance: Body mass index (BMI) may affect the 21-gene recurrence score (RS) in patients with ER-positive, ERBB2-negative breast cancer. If high BMI increases genomic risk in ER-positive, ERBB2-negative breast cancer, weight control will become more important. Objective: To assess the association between RS and BMI according to age groups and address BMI as a factor associated with high RS. Design, Setting, and Participants: This cohort study included 2295 patients with ER-positive, ERBB2-negative breast cancer who had undergone a multigene assay between March 29, 2010, and December 31, 2020, in 2 hospitals. All of the study patients were Korean women, and the median follow-up period was 45 months (range, 1-40 months). The correlations between continuous RS and BMI were investigated. A high BMI was defined as a body mass index greater than or equal to 25. In the younger age group (age ≤45 years), a high RS was defined as an RS of greater than 20. Exposures: Body mass index. Main Outcomes and Measures: The Pearson correlation coefficient was used to estimate the association between RS and BMI. A multivariable binary logistic model was used to identify high RS. Results: Among the 2295 women included (mean [SD] age, 49.8 [4.00] years; range, 22-81 years), 776 were aged 45 years or younger; RS and BMI were weakly correlated (correlation coefficient, 0.119; P < .001) in this younger group. Among them, the proportion of patients with an RS greater than 20 was significantly higher in the high BMI group than in the normal BMI group (45.5% [46 of 101] vs 27.3% [184 of 675]; P < .001). In the multivariable analysis, high BMI was an associated factor for high RS (odds ratio, 2.06; 95% CI, 1.28-3.32; P = .003). The 21-gene multigene assay-guided chemotherapy rate was significantly higher in patients with high BMI (30.7% [31 of 101] vs 20.2% [136 of 674]; P = .02). Conclusions and Relevance: In this cohort study of women aged 45 years or younger, high BMI was associated with higher RS in those with ER-positive, ERBB2-negative breast cancer; further studies are necessary to examine the underlying mechanisms.

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.

The Impact of Post-Mastectomy Radiotherapy on Survival Outcomes in Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy.

This study aimed to determine whether post-mastectomy radiotherapy (PMRT) is beneficial for the prognosis of patients who achieved pathologic complete response (pCR), or who had minimal residual disease, after undergoing neoadjuvant chemotherapy (NAC). Patients who underwent a total mastectomy between 2006 and 2018, after NAC, were included. Patients who did not receive PMRT were matched using 1:3 propensity score matching (PSM). Kaplan-Meier survival curves were used to compare locoregional recurrence-free survival (LRRFS) and overall survival (OS). A total of 368 patients were included after 1:3 PSM. PMRT improved the LRRFS (p = 0.016) and OS (p = 0.017) rates of patients who underwent NAC. However, PMRT did not affect the prognosis of patients with pCR (LRRFS: p = 0.999; OS: p = 0.453). In addition, PMRT had a limited effect on LRRFS and OS in patients who responded well to NAC, with a neoadjuvant response index (NRI) value of 0.7-1.0 (LRRFS: p = 0.568; OS: p = 0.875). PMRT improved the OS of patients with a large residual tumor burden, such as nodal metastases or pathologic stage II/III. The benefits of PMRT vary depending on the patients' response to NAC, although PMRT is useful for treating patients who underwent NAC. PMRT can be omitted, not only in patients with pCR, but also in good responders with an NRI value of 0.7-1.0.

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.

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.

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.

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.

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.

Validation of Clinical Treatment Score post-5 years (CTS5) risk stratification in premenopausal breast cancer patients and Ki-67 labelling index.

This study aimed to validate the Clinical Treatment Score post-5 years (CTS5)-based risk stratification in a cohort comprising pre- and postmenopausal patients with estrogen receptor (ER)-positive breast cancer. We investigated the clinicopathologic parameters including Ki-67 labelling index (LI) to identify factors affecting late distant recurrence (DR). Women with ER-positive breast cancer who were free of DR for 5 years were identified between January 2004 and December 2009. We investigated the risk of late DR (5-10 years) according to the CTS5 risk group. Cox regression analysis was used to determine the prognostic performance of CTS5 and identify factors associated with late DR. In all, 680 women were included. Of these, 379 (55.7%) were premenopausal and 301 (44.3%) were postmenopausal. At a median follow-up of 118 months, 32 women had late DR. CTS5 was a significant prognostic factor for late DR in both pre- and postmenopausal women. In the low CTS5 group, high Ki-67 LI (> 20%) was a significant risk factor for late DR. CTS5 is a useful tool for assessing the risk of late DR in pre- and postmenopausal women with ER-positive breast cancer. Extended endocrine therapy can be considered in patients with high Ki-67 LI (> 20%) in the low CTS5 group.

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.

Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy.

We aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398-0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691-3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167-3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.

Comparison of complications according to incision types in nipple-sparing mastectomy and immediate reconstruction.

BACKGROUND: Nipple-sparing mastectomy (NSM), followed by immediate reconstruction (IR) of the breast, has become a preferred surgical procedure with good cosmesis results and patient satisfaction. However, nipple-areolar complex (NAC) ischemia and necrosis remain major problems after NSM and IR. METHODS: We retrospectively analyzed patients who underwent NSM and IR at Gangnam Severance Hospital from January 2009 to June 2018. We compared the patient characteristics and complication rate among three different incisions (inframammary fold [IMF], radial, periareolar). Additionally, we identified the risk factors of NAC necrosis. RESULTS: Data from 290 eligible breasts in 275 patients were analyzed. Patients with IMF incision had relatively lower breast weights. The overall complication rate was the highest with periareolar incision and the lowest with IMF incision (42.6% vs. 18.8%, p < 0.001). The rate of NAC ischemia or necrosis was significantly different among the three incisions (9.7%, 17.0%, and 31.1% in IMF, radial, and periareolar, respectively; p < 0.001). Moreover, surgical treatments were more frequently needed in patients with periareolar incision. Periareolar incision, short distance from the tumor to the nipple base, and large breast weight were independent risk factors of NAC ischemia or necrosis in multivariable analysis. CONCLUSIONS: Compared with IMF incision, periareolar incision was associated with higher incidences of surgical complications and NAC necrosis. Careful consideration is needed when planning NSM in patients with a large breast volume or a tumor close to the nipple.