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.

Dynamic insights into infection risk over time in two-stage implant-based breast reconstruction: a retrospective cohort study.

BACKGROUND: Infections following postmastectomy implant-based breast reconstruction (IBR) can compromise surgical outcomes and lead to significant morbidity. This study aimed to discern the timing of infections in two-stage IBR and associated risk factors. METHOD: A review of electronic health records was conducted on 1,096 breasts in 1,058 patients undergoing two-stage IBR at ** National University Hospital (2015-2020). Infections following the first-stage tissue expander (TE) insertion and second-stage TE exchange were analyzed separately, considering associated risk factors. RESULTS: Over a median follow-up of 53.5 months, infections occurred in 2.9% (32/1096) after the first stage and 4.1% (44/1070) after the second stage. Infections following the first-stage procedure exhibited a bimodal distribution across time, while those after the second-stage procedure showed a unimodal pattern. When analyzing risk factors for infection after the first-stage procedure, axillary lymph node dissection (ALND) was associated with early (≤7 weeks) infection, while both ALND and obesity were independent predictors of late (>7 weeks) infection. For infections following the second-stage procedure, obesity, postmastectomy radiotherapy, a history of expander infection, ALND, and the use of textured implants were identified as independent risk factors. Postmastectomy radiotherapy was related to non-salvaged outcomes after infection following both stages. CONCLUSION: Infections following first and second-stage IBR exhibit distinct timelines reflecting different pathophysiology. Understanding these timelines and associated risk factors will inform patient selection for IBR and aid in tailored postoperative surveillance planning. These findings contribute to refining patient suitability for IBR and optimizing personalized postoperative care strategies.

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.

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.

Oncological Safety of Skipping Axillary Lymph Node Dissection in Patients with Clinical N0, Sentinel Node-Positive Breast Cancer Undergoing Total Mastectomy.

OBJECTIVE: This study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive. METHODS: This study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group. RESULTS: Mean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70-2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69-5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02). CONCLUSION: Collectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.

Potential Perturbations of Critical Cancer-regulatory Genes in Triple-Negative Breast Cancer Cells Within the Humanized Microenvironment of Patient-derived Xenograft Models.

PURPOSE: In this study, we aimed to establish humanized patient-derived xenograft (PDX) models for triple-negative breast cancer (TNBC) using cord blood (CB) hematopoietic stem cells (HSCs). Additionally, we attempted to characterize the immune microenvironment of the humanized PDX model to understand the potential implications of altered tumor-immune interactions in the humanized PDX model on the behavior of TNBC cells. METHODS: To establish a humanized mouse model, high-purity CD34+ HSCs from CB were transplanted into immunodeficient NOD scid γ mice. Peripheral and intratumoral immune cell compositions of humanized and non-humanized mice were compared. Additionally, RNA sequencing of the tumor tissues was performed to characterize the gene expression features associated with humanization. RESULTS: After transplanting the CD34+ HSCs, CD45+ human immune cells appeared within five weeks. A humanized mouse model showed viable human immune cells in the peripheral blood, lymphoid organs, and in the tumor microenvironment. Humanized TNBC PDX models showed varying rates of tumor growth compared to that of non-humanized mice. RNA sequencing of the tumor tissue showed significant alterations in tumor tissues from the humanized models. tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) is a shared downregulated gene in tumor tissues from humanized models. Silencing of TNFRSF11B in TNBC cell lines significantly reduced cell proliferation, migration, and invasion in vitro. Additionally, TNFRSF11B silenced cells showed decreased tumorigenicity and metastatic capacity in vivo. CONCLUSION: Humanized PDX models successfully recreated tumor-immune interactions in TNBC. TNFRSF11B, a commonly downregulated gene in humanized PDX models, may play a key role in tumor growth and metastasis. Differential tumor growth rates and gene expression patterns highlighted the complexities of the immune response in the tumor microenvironment of humanized PDX models.

Increased risk of contralateral breast cancer for BRCA1/2 wild-type, high-risk Korean breast cancer patients: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients. METHODS: We conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service's eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCA mutation group, the BRCAx group, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients. RESULTS: Among 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11-13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76-4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted. CONCLUSION: Breast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.

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.

Life-Threatening Hematoma in an Elderly Breast Cancer Patient Undergoing Chemotherapy.

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

A Survey of Practice Patterns for Clinical Nodal Staging Prior to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. MATERIALS AND METHODS: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. RESULTS: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. CONCLUSIONS: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation.

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.

Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer.

PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has significantly impacted the diagnosis and treatment of breast cancer. Our study investigated the change in diagnosis and treatment of breast cancer with the progress of COVID-19 pandemic. MATERIALS AND METHODS: The study group comprised 6,514 recently diagnosed breast cancer patients between January 1, 2019, and February 28, 2021. The patients were divided into two groups: pre-COVID-19 period (3,182; January 2019 to December 2019) and COVID-19 pandemic period (3,332; January 2020 to February 2021). Clinicopathological information related to the first treatment after breast cancer diagnosis was retrospectively collected and analyzed in the two groups. RESULTS: Among the 6,514 breast cancer patients, 3,182 were in the pre-COVID-19 period and 3,332 were in the COVID-19 pandemic period. According to our evaluation, the least breast cancer diagnosis (21.8%) was seen in the first quarter of 2020. The diagnosis increased gradually except for the fourth quarter in 2020. While early-stage breast cancer was diagnosed 1,601 (48.1%) during the COVID-19 pandemic (p=0.001), the number of surgical treatments increased 4.6% (p < 0.001), and the treatment time was slightly shorter 2 days (p=0.001). The breast cancer subtype distribution was not statistically different between the pre-COVID-19 and COVID-19 period groups. CONCLUSION: In the early stages of the pandemic, the number of breast cancer cases temporarily decreased; however, they stabilized soon, and no significant differences could be identified in the diagnosis and treatment when compared to the period before the pandemic.

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.

AKR1C2 Promotes Metastasis and Regulates the Molecular Features of Luminal Androgen Receptor Subtype in Triple Negative Breast Cancer Cells.

PURPOSE: Patients with triple-negative breast cancer (TNBC) have an increased risk of distant metastasis compared to those with other subtypes. In this study, we aimed to identify the genes associated with distant metastasis in TNBC and their underlying mechanisms. METHODS: We established patient-derived xenograft (PDX) models using surgically resected breast cancer tissues from 31 patients with TNBC. Among these, 15 patients subsequently developed distant metastases. Candidate metastasis-associated genes were identified using RNA sequencing. In vitro wound healing, proliferation, migration, and invasion assays and in vivo tumor xenograft and metastasis assays were performed to determine the functional importance of aldo-keto reductase family 1 member C2 (AKR1C2). Additionally, we used the METABRIC dataset to investigate the potential role of AKR1C2 in regulating TNBC subtypes and their downstream signaling activities. RESULTS: RNA sequencing of primary and PDX tumors showed that genes involved in steroid hormone biosynthesis, including AKR1C2, were significantly upregulated in patients who subsequently developed metastasis. In vitro and in vivo assays showed that silencing of AKR1C2 resulted in reduced cell proliferation, migration, invasion, tumor growth, and incidence of lung metastasis. AKR1C2 was upregulated in the luminal androgen receptor (LAR) subtype of TNBC in the METABRIC dataset, and AKR1C2 silencing resulted in the downregulation of LAR classifier genes in TNBC cell lines. The androgen receptor (AR) gene was a downstream mediator of AKR1C2-associated phenotypes in TNBC cells. AKR1C2 expression was associated with gene expression pathways that regulate AR expression, including JAK-STAT signaling or interleukin 6 (IL-6). The levels of phospho-signal transducer and activator of transcription and IL-6, along with secreted IL-6, were significantly downregulated in AKR1C2-silenced TNBC cells. CONCLUSION: Our data indicate that AKR1C2 is an important regulator of cancer growth and metastasis in TNBC and may be a critical determinant of LAR subtype features.

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial.

BACKGROUND: Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. FINDINGS: This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. CONCLUSIONS: The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT.

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.

The percentage of unnecessary mastectomy due to false size prediction using preoperative ultrasonography and MRI in breast cancer patients who underwent neoadjuvant chemotherapy: a prospective cohort study.

BACKGROUND: Imaging-estimated tumour extent after neoadjuvant chemotherapy tends to be discordant with the pathological extent. The authors aimed to prospectively determine the proportion of decisions regarding total mastectomy for potential breast-conserving surgery candidates owing to false size prediction with imaging in neoadjuvant chemotherapy and non-neoadjuvant chemotherapy patients. MATERIALS AND METHODS: The authors prospectively enroled clinical stage II or III breast cancer patients who are scheduled for total mastectomy between 2018 and 2021. This study was conducted at Seoul National University Hospital at South Korea. Before surgery, each surgeon recorded the hypothetical maximum tumour size at which the surgeon would have been able to attempt breast-conserving surgery if the patient had actually less than the size of the tumour at that location in the breast. After surgery, the hypothetical maximum tumour size was compared with the final pathologic total extent of the tumour, including invasive and in situ cancers. RESULTS: Among the 360 enroled patients, 130 underwent neoadjuvant chemotherapy, and 230 did not undergo neoadjuvant chemotherapy. Of the total of each group, 47.7% in the neoadjuvant chemotherapy group and 21.3% in the non-neoadjuvant chemotherapy group had a smaller pathologic tumour extent than the pre-recorded hypothetical maximum tumour size (P<0.001). Further analyses were conducted for the neoadjuvant chemotherapy group. The proportions of total mastectomy with false size prediction were higher in HER2-positive (63.3%) and triple-negative (57.6%) patients compared with ER-positive/HER2-negative (25.0%) patients (P<0.001). Both magnetic resonance imaging-pathology and ultrasonography-pathology size discrepancies were significantly associated with false decisions for total mastectomy (both P<0.001). Without magnetic resonance imaging, the false decision may be reduced by 21.5%. CONCLUSION: A total of 47.7% of patients who received total mastectomy after neoadjuvant chemotherapy were breast-conserving surgery eligible, which was significantly higher than that of non-neoadjuvant chemotherapy patients. Magnetic resonance imaging contributed the most to false size predictions.