Evaluating the feasibility of repeat sentinel lymph node biopsy in ipsilateral breast tumor recurrence: Technical considerations and oncologic outcomes.

INTRODUCTION: Ipsilateral breast tumor recurrence (IBTR) remains a concern despite standard treatments. Advances in early detection have shifted surgical paradigms towards less invasive approaches. While repeat sentinel lymph node biopsy (rSLNB) emerges as a viable option according to the 2023 National Comprehensive Cancer Network (NCCN) guidelines, its efficacy remains uncertain. This study aimed to assess lymphatic drainage patterns in IBTR and evaluate the feasibility of rSLNB, along with analyzing oncologic outcomes. METHODS: A retrospective analysis involving 78 patients with IBTR who had prior breast-conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) and adjuvant whole breast irradiation (WBI) at Samsung Medical Center was conducted. Data on patient characteristics, lymphatic mapping techniques, and oncologic outcomes were collected and analyzed. RESULTS: Among 78 patients with IBTR, 82.1 % underwent successful rSLNB, predominantly detecting lymphatic drainage to the ipsilateral axilla (80.8 %). The initial tumor location correlated significantly with failed lymphatic mapping (p = 0.019). A third event occurred in 28.8 % of invasive IBTR cases, notably associated with postmenopausal status, higher T stages, and HR(-)/HER2(-) subtype (p < 0.001). The risk of a third event increased by over 50 % within a 2-year interval post-IBTR. CONCLUSION: rSLNB in patients with IBTR, particularly for tumors initially located outside the upper-outer quadrant, demonstrated technical feasibility. The combined use of blue dye with lymphoscintigraphy may enhance rSLNB success rates. Active surveillance, especially for triple negative IBTR cases, may be important due to their aggressive nature and rapid progression potential within a short interval post-IBTR.

Nonsentinel lymph node metastases in cases of micrometastasis detected by sentinel lymph node biopsy after neoadjuvant chemotherapy.

BACKGROUND: There is a clinical need to omit axillary lymph node dissection (ALND) when residual disease in sentinel lymph nodes (SLNs) is low after neoadjuvant chemotherapy (NAC). This study aimed to clarify the relationship between micrometastasis in SLNs after NAC and additional non-SLN metastases by analyzing SLN biopsy results followed by ALND. METHODS: This retrospective study reviewed clinical records of patients who underwent breast cancer surgery between January 2010 and June 2022 after NAC at Samsung Medical Center. Of 3944 patients, 806 underwent SLN biopsy followed by ALND. Intraoperative frozen SLN biopsy results were examined, including the number and size of metastases in SLNs, and further investigated the number of additional non-SLN metastases. RESULTS: Among the 806 patients, 95 (11.8%) had micrometastasis on SLNs in frozen sections, of which 89 (93.7%) had clinically node-positive (cN1-3) breast cancer before NAC. Twenty-three patients (24.2%) exhibited positive additional non-SLNs after ALND. The presence of lymphovascular invasion (vs. absence; odds ratio [OR] = 4.02, p = .0151) and having two or more SLNs with micrometastasis (vs. a positive SLN; OR = 3.65, p = .0301) were significantly associated with additional non-SLN metastases. Tumor subtypes and breast pathological complete response after NAC showed no correlation with the additional non-SLN metastases. CONCLUSION: The study identified a 24.2% possibility of additional non-SLN metastasis if micrometastases was detected in the SLN after NAC. This rate is significant, indicating that ALND cannot be omitted if low volume residual disease, such as micrometastasis, is identified in the SLN after NAC.

METTL18 functions as a Phenotypic Regulator in Src-Dependent Oncogenic Responses of HER2-Negative Breast Cancer.

Methyltransferase-like (METTL)18 has histidine methyltransferase activity on the RPL3 protein and is involved in ribosome biosynthesis and translation elongations. Several studies have reported that actin polymerization serves as a Src regulator, and HSP90 is involved in forming polymerized actin bundles. To understand the role of METTL18 in breast cancer and to demonstrate the importance of METTL18 in HER-2 negative breast cancer metastasis, we used biochemical, molecular biological, and immunological approaches in vitro (breast tumor cell lines), in vivo (tumor xenograft model), and in samples of human breast tumors. A gene expression comparison of 31 METTL series genes and 22 methyltransferases in breast cancer patients revealed that METTL18 is highly amplified in human HER2-negative breast cancer. In addition, elevated levels of METTL18 expression in patients with HER2-negative breast cancer are associated with poor prognosis. Loss of METTL18 significantly reduced the metastatic responses of breast tumor cells in vitro and in vivo. Mechanistically, METTL18 indirectly regulates the phosphorylation of the proto-oncogene tyrosine-protein kinase Src and its downstream molecules in MDA-MB-231 cells via METTL18-mediated RPL3 methylation, which is also involved in determining HSP90 integrity and protein levels. In confocal microscopy and F/G-actin assays, METTL18 was found to induce actin polymerization via HSP90. Molecular events involving METTL18, RPL3, HSP90, and actin polymerization yielded Src phosphorylated at both tyrosine 419 and tyrosine 530 with kinase activity and oncogenic functions. Therefore, it is suggested that the METTL18-HSP90-Actin-Src regulatory axis plays critical oncogenic roles in the metastatic responses of HER2-negative breast cancer and could be a promising therapeutic target.

Measuring patient-reported distress from breast magnetic resonance imaging: Development and validation of the MRI-related distress scale (MRI-DS).

OBJECTIVE: Although breast magnetic resonance imaging (MRI) is a valuable screening tool, breast MRI testing burden was associated with cancer worry and quality of life. We aimed to develop and validate the MRI-related distress scale (MRI-DS) to assess comprehensive distress specifically related to breast MRI. METHODS: We enrolled women aged above 18 years, diagnosed breast cancer, had MRI examination at least one time, and who could speak and read Korean in phase I and enrolled women aged above 18 years, visited outpatient clinic of breast general surgery, had undergone MRI examination at least once, and could speak and read Korean in phase II. We excluded patients who had any physical or psychiatric conditions in both phases. We recruited from a tertiary university-based hospital in South Korea between April and August 2023. RESULTS: All 18 items had acceptable levels of item correlation (≥0.30) in the explanatory factor analysis with a four-factor solution. The fit indices for the four-factor solution model were good. The discriminant validity of the MRI-DS had a moderate correlation with general anxiety or quality of life. In the known-group analysis, those who reported MRI as the most burden breast examination had higher total scores. CONCLUSION: The validity of the MRI-DS has been confirmed as a scale for measuring the specific distress caused by breast MRI. The MRI-DS is recommended to health professional to communicate with patients with MRI. CLINICAL IMPLICATIONS: It can be used to assess the distress associated with MRI screening in breast cancer patients. Physician could use MRI-DS to discuss the reasons for distress caused by breast MRI screening and to address specific sources of discomfort associated with it.

Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel.

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSµC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSµC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 µm) toward the inner wall, while directing smaller ones (avg. diameter: 23 µm) outward. Utilizing ITSµC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSµC suggests its potential in differentiating a wide range of heterogeneous cell populations.

Prognostic value of structural variants in early breast cancer patients.

Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.

The Prognostic Impact of HER2-Low and Menopausal Status in Triple-Negative Breast Cancer.

TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed.

Migratory Tumor Cells Cooperate with Cancer Associated Fibroblasts in Hormone Receptor-Positive and HER2-Negative Breast Cancer.

Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment.

Endoxifen Concentration is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dosage. However, the clinical significance of endoxifen on the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics. Conclusion: Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

PURPOSE: We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. PATIENTS AND METHODS: POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. RESULTS: Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). CONCLUSION: In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Plant-Derived Anti-Human Epidermal Growth Factor Receptor 2 Antibody Suppresses Trastuzumab-Resistant Breast Cancer with Enhanced Nanoscale Binding.

Traditional monoclonal antibodies such as Trastuzumab encounter limitations when treating Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer, particularly in cases that develop resistance. This study introduces plant-derived anti-HER2 variable fragments of camelid heavy chain domain (VHH) fragment crystallizable region (Fc) KEDL(K) antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncover the antibody's nanoscale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN force resistance and bond lifetimes in the second range. The antibody demonstrates a specific affinity for HER2-positive breast cancer cells, including those that are Trastuzumab-resistant. Moreover, in immune-deficient mice, the plant-derived anti-HER2 VHH-FcK antibody exhibits superior antitumor activity, especially against tumors that are resistant to Trastuzumab. These findings underscore the plant-derived antibody's potential as an impactful immunotherapeutic strategy for treating Trastuzumab-resistant HER2-positive breast cancer.

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor ß diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

The Effects of National Insurance Coverage Expansion and Genetic Counseling's Role on BRCA1/2 Mutation Tests in Breast Cancer Patients.

PURPOSE: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. MATERIALS AND METHODS: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. RESULTS: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. CONCLUSION: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

PURPOSE: The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. METHODS: ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. DISCUSSION: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Impact of residual microcalcifcations on prognosis after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues.

Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.

Comprehensive Young Age Breast Cancer registry from clinical, genomics, and patient-reported outcomes measured with 15 years follow-up: the CHARM cohort profile.

BACKGROUND: In recognition of the distinct clinical challenges and research gaps in young breast cancer (YBC) patients, we established the Comprehensive Young Age Breast Cancer (CHARM) registry to collect prospective data. METHODS: This prospective cohort included patients who were newly diagnosed with histologically confirmed breast cancer without prior treatment at the Samsung Medical Center (SMC) in April 2013. We included patients who were either 40 years old or younger at the time of diagnosis, pregnant at breast cancer diagnosis or diagnosed with breast cancer within 1 year of delivery. All data were collected using Medidata's Rave Electronic Data. Clinical data were obtained from electronic medical records. Two experienced pathologists reviewed the pathologic data. Bone mineral densitometry tests have been conducted annually. To obtain multi-omics data, tumor tissues and blood samples were prospectively collected from consenting patients in the registry during surgery. The fertility-related factor also collected collaborated with the Department of Obstetrics and Gynecology. Anti-Müllerian hormone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were measured using an additional blood sample from baseline to last follow-up. Patient-reported outcomes were assessed using mobile questionnaires. RESULTS: A total of 1868 participants were included in the SMC YBC study. The average (standard deviation) age was 35.57 (3.79) and 99.8% of the participants were premenopausal. Among them, 1062 participants completed the PRO questionnaires. CONCLUSIONS: The SMC YBC cohort serves as a comprehensive registry for YBC to optimize care and improve knowledge regarding the management of YBC.

Social support during re-entry period and long-term quality of life in breast cancer survivors: a 10-year longitudinal cohort study.

PURPOSE: This study evaluated the association between social support during the re-entry period and long-term health-related quality of life (HRQoL) in breast cancer survivors using a longitudinal cohort study. METHODS: This is a prospective cohort study with 275 breast cancer survivors who reported HRQoL at 5 and 10 years after diagnosis. Social support for the re-entry period was measured 3 years after diagnosis using the Medical Outcome Study Social Support Survey (MOS-SSS). HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Breast Cancer-Specific Module (BR-23). Multivariable linear regression analysis was performed to evaluate HRQoL at 5 and 10 years after diagnosis by level of social support during the re-entry period. RESULTS: The mean (SD) of social support during re-entry period was 68.5. The low social support (LSS, score < 55) group during the re-entry period had a significantly lower HRQoL (mean difference = - 12.93) compared to moderate or high social support (MHSS, score ≥ 55) group. 5 and 10 years after diagnosis, the LSS group continued to demonstrate lower HRQoL (5 years: - 7.17; 10 years: - 7.85) compared to the MHSS group. The LSS group were more likely to have lower role and social function scores, and higher fatigue, pain, and financial problems compared to the MHSS group at 10 years after diagnosis. CONCLUSIONS: Breast cancer survivors who received lower social support during the re-entry period were more likely to experience poorer HRQoL in the long term than those who did not.