Survival After Contralateral Axillary Metastasis in Breast Cancer.

BACKGROUND: Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. METHODS: This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). RESULTS: The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). CONCLUSION: The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent.

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.

Comparison of long-term oncologic outcomes of central lumpectomy and conventional breast-conserving surgery for invasive breast cancer: propensity score matching analysis.

PURPOSE: Central lumpectomy (CL) is a breast-conserving surgical (BCS) technique that involves excision of the nipple-areolar complex with breast tumor in centrally located breast cancers. We aimed to investigate the long-term clinical outcomes of CL in comparison with conventional BCS (cBCS). METHODS: Patient records who underwent BCS with clear resection margins for invasive breast cancer between 2004 and 2018 were retrospectively reviewed. Of the total 6,533 patients, 106 (1.6%) underwent CL. Median follow-up duration was 73.4 months. 1:3 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize selection bias. RESULTS: The CL group showed a significantly higher ipsilateral breast tumor recurrence (IBTR) rate than the cBCS group (10-year IBTR rate: 5.8% vs. 3.1%, p = 0.004), even after adjusting for other variables (hazard ratio (HR), 2.65; 95% confidence interval (CI), 1.07-6.60, p = 0.048). However, there were no significant differences observed in regional recurrence, distant metastasis, or overall survival rates between the two groups. Both PSM and IPTW analyses showed significantly higher IBTR in the CL group (PSM HR, 3.27; 95% CI, 0.94-11.36; p = 0.048 and IPTW HR, 4.66; 95%CI, 1.85-11.77; p < 0.001). Lastly, when analyzing 2,213 patients whose tumors were located within 3 cm of the nipple, the CL group showed a significantly higher IBTR than the cBCS group before and after PSM. CONCLUSION: CL was associated with a higher rate of IBTR compared to cBCS, while other survival outcomes were comparable. For centrally located tumors, CL may be considered for patients preferring breast preservation. However, higher risk for IBTR should be informed and careful surveillance may be necessary during the early post-operative follow-up periods.

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

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

Residual Risk of Ipsilateral Tumor Recurrence in Patients Who Achieved Clear Lumpectomy Margins After Repeated Resection.

PURPOSE: Patients with breast cancer with positive lumpectomy margins have a two-fold increased risk of ipsilateral breast tumor recurrence (IBTR). This can be the result of either technically incomplete resection or the biological characteristics of the tumor that lead to a positive margin. We hypothesized that if achieving negative margins by re-excision nullifies the IBTR risk, then the increased risk is mainly attributed to the technical incompleteness of the initial surgeries. Thus, we investigated IBTR rates in patients with breast cancer who achieved clear margins after re-excision. METHODS: We retrospectively reviewed patients who underwent breast lumpectomy for invasive breast cancer between 2004 and 2018 at a single institution, and investigated IBTR events. RESULTS: Among 5,598 patients, 793 achieved clear margins after re-excision of their initial positive margins. During the median follow-up period of 76.4 months, 121 (2.2%) patients experienced IBTR. Patients who underwent re-excision to achieve negative margin experienced significantly higher IBTR rates compared to those achieving clear margin at first lumpectomy (10-year IBTR rate: 5.3% vs. 2.6% [25 vs. 84 events]; unadjusted p = 0.031, hazard ratio, 1.61, 95% confidence interval [CI], 1.04-2.48; adjusted p = 0.030, hazard ratio, 1.69, 95% CI, 1.05-2.72). This difference was more evident in patients aged < 50 years and those with delayed IBTR. Additionally, no statistically significant differences were observed in the spatial distribution of IBTR locations. CONCLUSION: Patients who underwent re-excision for initial positive margins had an increased risk of IBTR, even after achieving a final negative margin, compared to patients with negative margins initially. This increased risk of IBTR is mostly observed in young patients and delayed cases.

Prognostic Implication of Focal Breast Edema on Preoperative Breast Magnetic Resonance Imaging in Breast Cancer Patients.

PURPOSE: In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edema-negative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson's χ² test, Kaplan-Meier estimator, and Cox proportional hazards model. RESULTS: There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively. The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs. 19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56-9.11) and recurrence-free survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94-4.63) than those in the ENG. After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05-27.15). CONCLUSION: Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.

Comparison of Quality of Life and Cosmetic Outcome of Latissimus Dorsi Mini-Flap With Breast Conservation Surgery Without Reconstruction.

PURPOSE: Latissimus dorsi mini-flap (LDMF) reconstruction after breast-conserving surgery (BCS) is a useful volume replacement technique when a large tumor is located in the upper or outer portion of the breast. However, few studies have reported the impact of LDMF on patients' quality of life (QoL) and cosmesis compared with conventional BCS. METHODS: We identified patients who underwent BCS with or without LDMF between 2010 and 2020 at a single center. At least 1 year after surgery, we prospectively administered the BREAST-Q to assess QoL and obtained the patients' breast photographs. The cosmetic outcome was assessed using four panels composed of physicians and the BCCT.core software. RESULTS: A total of 120 patients were enrolled, of whom 62 and 58 underwent LDMF or BCS only, respectively. The LDMF group had significantly larger tumors, shorter nipple-to-tumor distances in preoperative examinations, and larger resected breast volumes than did the BCS-only group (p < 0.001). The questionnaires revealed that QoL was poorer in the LDMF group, particularly in terms of the physical well-being score (40.9 vs. 20.1, p < 0.001). Notably, the level of patients' cosmetic satisfaction with their breasts was comparable, and the cosmetic evaluation was assessed by panels and the BCCT.core software showed no differences between the groups. CONCLUSION: Our results showed that cosmetic outcomes of performing LDMF are comparable to those of BCS alone while having the advantage of resecting larger volumes of breast tissue. Therefore, for those who strongly wish to preserve the cosmesis of their breasts, LDMF can be considered a favorable surgical option after the patient is oriented toward the potential for physical dysfunction after surgery.

Locoregional Recurrence Patterns in Patients With Different Molecular Subtypes of Breast Cancer.

Importance: While numerous studies have consistently reported that the molecular subtypes of breast cancer (BC) are associated with different patterns of distant metastasis, few studies have investigated the association of tumor subtypes with locoregional recurrence. Objective: To investigate the patterns of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), and contralateral BC (CBC) according to tumor subtypes. Design, Setting, and Participants: This retrospective cohort study used the clinical records of patients who underwent BC surgery at a single institution in South Korea between January 2000 and December 2018. Data were analyzed from May 1, 2019, to February 20, 2023. Exposures: Ipsilateral breast tumor recurrence, RR, and CBC events. Main Outcomes and Measures: The primary outcome was differences in annual incidence patterns of IBTR, RR, and CBC according to tumor subtypes. Hormone receptor (HR) status was assessed by immunohistochemical staining assay, and ERBB2 status was evaluated according to American Society of Clinical Oncology and College of American Pathologists guidelines. Results: A total of 16 462 female patients were included in the analysis (median age at time of operation, 49.0 years [IQR, 43.0-57.0 years]). The 10-year IBTR-, RR-, and CBC-free survival rates were 95.9%, 96.1%, and 96.5%, respectively. On univariate analysis, HR-/ERBB2+ tumors had the worst IBTR-free survival (vs HR+/ERBB2- subtype: adjusted hazard ratio, 2.95; 95% CI, 2.15-4.06), while the HR-/ERBB2- subtype had the worst RR- and CBC-free survival among all subtypes (vs HR+/ERBB2- subtype, RR: adjusted hazard ratio, 2.95; 95% CI, 2.37-3.67; CBC: adjusted hazard ratio, 2.12; 95% CI, 1.64-2.75). Subtype remained significantly associated with recurrence events in Cox proportional hazards regression analysis. Regarding the annual recurrence pattern, the IBTR patterns of HR-/ERBB2+ and HR-/ERBB2- subtypes showed double peaks, while HR+/ERBB2- tumors showed a steadily increasing pattern without distinguishable peaks. Additionally, the HR+/ERBB2- subtype seemed to have a steady RR pattern, but other subtypes showed the highest RR incidence at 1 year following surgery, which then gradually decreased. The annual recurrence incidence of CBC gradually increased among all subtypes, and patients with the HR-/ERBB2- subtype had a higher incidence than patients with other subtypes over 10 years. Younger patients (age ≤40 years) had greater differences in IBTR, RR, and CBC patterns between subtypes than did older patients. Conclusions and Relevance: In this study, locoregional recurrence occurred with different patterns according to BC subtypes, with younger patients having greater differences in patterns among subtypes than older patients. The findings suggest that tailoring surveillance should be recommended regarding differences in locoregional recurrence patterns according to tumor subtypes, particularly for younger patients.

Triple-Negative Breast Cancer-Derived Extracellular Vesicles Promote a Hepatic Premetastatic Niche via a Cascade of Microenvironment Remodeling.

Patients with triple-negative breast cancer (TNBC) often develop metastases in visceral organs including the liver, but the detailed molecular mechanisms of TNBC liver metastasis is not clearly understood. In this study, we tried to dissect the process of premetastatic niche formation in the liver by using patient-derived xenograft (PDX) models of TNBC with different metastatic propensity. RNA sequencing of TNBC PDX models that successfully metastasized to liver showed upregulation of the Cx3cr1 gene in the liver microenvironment. In syngeneic breast cancer models, the Cx3cr1 upregulation in liver preceded the development of cancer cell metastasis and was the result of recruitment of CX3CR1-expressing macrophages. The recruitment was induced by the CX3CL1 production from the liver endothelial cells and this CX3CL1-CX3CR1 signaling in the premetastatic niche resulted in upregulation of MMP9 that promoted macrophage migration and cancer cell invasion. In addition, our data suggest that the extracellular vesicles derived from the breast cancer cells induced the TNFα expression in liver, which leads to the CX3CL1 upregulation. Lastly, the plasma CX3CL1 levels in 155 patients with breast cancer were significantly associated with development of liver metastasis. IMPLICATIONS: Our data provides previously unknown cascades regarding the molecular education of premetastatic niche in liver for TNBC.

Retrospective Cohort Study on the Long-term Oncologic Outcomes of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope Mapping) in Early Breast Cancer: A Propensity Score-Matched Analysis.

PURPOSE: In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer. Materials and Methods: This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group). RESULTS: The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node-positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node-positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups. CONCLUSION: Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.

Association of body composition fat parameters and breast density in mammography by menopausal status.

We investigated the relationship between body fat-driven obesity and breast fat density in mammography according to menopausal status. We retrospectively analyzed 8537 women (premenopausal, n = 4351; postmenopausal, n = 4186). Body fat parameters included BMI (body mass index), waist circumference (WC), waist-hip ratio (WHR), fat mass index (FMI), Percentage of body fat (PBF), and visceral fat area (VFA). Body fat-driven obesity was defined as follows: overall obesity, BMI ≥ 25 kg/m2; central obesity, WC > 85 cm; abdominal obesity, WHR > 0.85; excessive FMI, the highest quartile (Q4) of FMI; excessive PBF, the highest quartile (Q4) of VFA; visceral obesity, and the highest quartile (Q4) of VFA). Breast density was classified according to BI-RADS (grade a, b, c, and d), which defined as an ordinal scale (grade a = 1, grade b = 2, grade c = 3, and grade d = 4). All body fat-driven obesity parameters were negatively associated with the grade of breast density in both groups of women (p < 0.001): The more fatty parameters are, the less dense breast is. In multivariable binary logistic regression, all body fat-driven obesity parameters also showed a negative association with grade d density (vs. grade a, b, or c). In premenopausal women, BMI was a more associated parameter with grade d density than those of the other fat-driven parameters (OR 0.265, CI 0.204-0.344). In postmenopausal women, WC was more associated with grade d density than the others (OR 0.315, CI 0.239-0.416). We found that BMI, WC, WHR, FMI, PBF and VFA were negatively correlated with dense breast, and the association degree pattern between body fat-driven obesity and dense breast differs according to menopausal status.

Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy.

PURPOSE: The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer. METHODS: We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea. RESULTS: The 786 patients in the pathologic complete response group (RpCR) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R0) and the 68 patients in involved RM and non-pCR group (R1) (vs. R0, p = 0.001; vs. R1, p = 0.049). Patients in R0 showed no benefit in LRFS compared to R1 on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R0 and R1 group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS. CONCLUSION: Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches.

Epitranscriptomic features, such as single-base RNA editing, are sources of transcript diversity in cancer, but little is understood in terms of their spatial context in the tumour microenvironment. Here, we introduce spatial-histopathological examination-linked epitranscriptomics converged to transcriptomics with sequencing (Select-seq), which isolates regions of interest from immunofluorescence-stained tissue and obtains transcriptomic and epitranscriptomic data. With Select-seq, we analyse the cancer stem cell-like microniches in relation to the tumour microenvironment of triple-negative breast cancer patients. We identify alternative splice variants, perform complementarity-determining region analysis of infiltrating T cells and B cells, and assess adenosine-to-inosine base editing in tumour tissue sections. Especially, in triple-negative breast cancer microniches, adenosine-to-inosine editome specific to different microniche groups is identified.

Ipsilateral Lymphadenopathy After COVID-19 Vaccination in Patients With Newly Diagnosed Breast Cancer.

This study aimed to evaluate the imaging and pathological findings in axillary lymph nodes in patients with breast cancer who received concurrent ipsilateral coronavirus disease 2019 (COVID-19) vaccination. Of the 19 women with breast cancer who received concurrent COVID-19 vaccination shot in the arm ipsilateral to breast cancer, axillary lymphadenopathy was observed in 84.2% (16 of 19) of patients on ultrasound (US) and 71.4% (10 of 14) of patients on magnetic resonance imaging (MRI), and 21.0% (4 of 19) of patients were diagnosed with metastasis. Abnormal US and MRI findings of cortical thickening, effacement of the fatty hilum, round shape, and asymmetry in the number or size relative to the contralateral side were noted in more than half of the non-metastatic and metastatic lymph nodes; however, statistical significance was not noted. Axillary lymphadenopathy is commonly observed in patients with breast cancer who receive concurrent ipsilateral COVID-19 vaccination without specific differential imaging features. Thus, understanding the limitations of axillary imaging and cautious interpretation is necessary to avoid overestimation or underestimation of the axillary disease burden.

Clinical comparison between the presence and absence of protein plugs in pediatric choledochal cysts: experience in 390 patients over 30 years in a single center.

PURPOSE: The incidence of choledochal cyst (CC) with protein plugs is between 15.5%-40.4%. However, studies on CCs with protein plugs in children are limited. We aimed to analyze the clinical features, surgical findings, and complications of pediatric CCs with and without protein plugs. METHODS: We retrospectively analyzed 390 patients who underwent surgery for CCs between January 1987 and September 2017. The patients were divided into 2 groups: groups A (CC with protein plugs) and B (CC without protein plugs). The presence of protein plugs was evaluated using preoperative images or identified during surgery. RESULTS: One hundred forty-two (36.4%) patients had protein plugs in the pancreaticobiliary duct. The most common initial clinical presentation was abdominal pain, and its incidence was significantly higher in group A (66.2%) than in group B (54.8%) (P = 0.032). The incidence of accompanying pancreatitis was also significantly higher in group A (37.3% vs. 27.0%) (P = 0.040). Anomalous pancreaticobiliary ductal union (APBDU) was found in 261 patients (66.9%) and its incidence was significantly higher in group A (74.6% vs. 62.5%) (P = 0.014). Most protein plugs were found in the cyst (88.0%) and common channel (31.7%). The incidence of early complications was higher in group A; conversely, that of late complications did not differ. CONCLUSION: Approximately 36.4% of the pediatric CC patients were accompanied by protein plugs. Abdominal pain, pancreatitis, and APBDU were more commonly observed among those with protein plugs than among those without; long-term complications did not differ between them.

Impact of Trastuzumab on Ipsilateral Breast Tumor Recurrence for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer after Breast-Conserving Surgery.

PURPOSE: Trastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes. METHODS: We retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group). RESULTS: Propensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%; p = 0.002). The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07-8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer. CONCLUSION: Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.

PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Intensity of metastasis screening and survival outcomes in patients with breast cancer.

Previous randomized trials, performed decades ago, showed no survival benefit of intensive screening for distant metastasis in breast cancer. However, recent improvements in targeted therapies and diagnostic accuracy of imaging have again raised the question of the clinical benefit of screening for distant metastasis. Therefore, we investigated the association between the use of modern imaging and survival of patients with breast cancer who eventually developed distant metastasis. We retrospectively reviewed data of 398 patients who developed distant metastasis after their initial curative treatment between January 2000 and December 2015. Patients in the less-intensive surveillance group (LSG) had significantly longer relapse-free survival than did patients in the intensive surveillance group (ISG) (8.7 vs. 22.8 months; p = 0.002). While the ISG showed worse overall survival than the LSG did (50.2 vs. 59.9 months; p = 0.015), the difference was insignificant after adjusting for other prognostic factors. Among the 225 asymptomatic patients whose metastases were detected on imaging, the intensity of screening did not affect overall survival. A small subgroup of patients showed poor survival outcomes when they underwent intensive screening. Patients with HR-/HER2 + tumors and patients who developed lung metastasis in the LSG had better overall survival than those in the ISG did. Highly intensive screening for distant metastasis in disease-free patients with breast cancer was not associated with significant survival benefits, despite the recent improvements in therapeutic options and diagnostic techniques.