TPS618 Background: It is unclear whether the clinical benefit of cytotoxic adjuvant chemotherapy (CT) could be replaced by ovarian-function suppression (OFS) in premenopausal, estrogen receptor (ER)+HER2- breast cancer patients who have high clinical risk score and low genomic risk assessed by multigene assays. The TAILORx trial included a subgroup of premenopausal women with high clinical risk scores and midrange RS scores and found that CT, in addition to endocrine treatment (ET), offered clear benefits in terms of invasive disease-free survival (iDFS) and distant-recurrence-free survival (DRFS) compared to ET alone. However, a majority of the patients did not receive OFS, and the use of OFS as an alternative to chemotherapy in this population is still an area of ongoing research and debate. In addition, in premenopausal women of the RxPonder trial, which enrolled node-positive disease, it is noted that the addition of OFS to ET for at least 12 months improved iDFS numerically in the ET-alone arm, although this improvement did not reach statistical significance. We hypothesized that a favorable DRFS could be achieved by OFS plus ET without CT in premenopausal, pN1, ER+HER2- breast cancer with low genomic risk identified by an NGS-based multigene assay, the OncoFREE. Methods: The INTERSTELLAR trial is a prospective, multicenter, single-arm, non-inferiority clinical study. Premenopausal women aged ≤50 years with pT1-2 ER+HER2- breast cancer and 1-3 lymph node metastasis will be enrolled. They will be tested with OncoFREE, an NGS-based breast cancer prognosis multigene assay developed and available in South Korea, where a higher portion of the patients is premenopausal. Patients with low genomic risk (Decision Index≤20) are administered OFS plus tamoxifen or an aromatase inhibitor for five years. We hypothesize that the 5-year DRFS of the single arm treated with OFS plus ET would be not inferior to 96.1%, which is observed in the chemo-ET arm from the premenopausal subgroup of the RxPonder trial. The one-sided test with a non-inferiority margin of 3% and statistical power of 80% at a significance level of 0.05 resulted in a sample size of 380 patients with low genomic risk. Considering a 70% designation to low genomic risk by OncoFREE and a 10% drop-out rate, 604 patients will be enrolled from 15 tertiary care hospitals in South Korea. The primary endpoint will be tested in the 380 patients with low genomic risk. The patients with high genomic risk will receive CT followed by ET and will be followed for survival analysis as a secondary end-point. The trial has not enrolled its first patient yet at the time of submission. Clinical trial information: NCT05333328 .

BACKGROUND:Robot-assisted nipple-sparing mastectomy (R-NSM) was developed to minimize visible scarring and improve the quality of life in patients with breast cancer. However, despite its increasing adoption, evidence regarding its oncologic outcomes remains sparse. This study aimed to compare the oncologic outcomes of R-NSM and conventional nipple-sparing mastectomy (C-NSM). METHODS:We retrospectively reviewed patients who underwent NSM with immediate breast reconstruction for breast cancer between 2019 and 2022. Risk-reducing cases were excluded. R-NSM and C-NSM groups were compared after propensity score matching using a nearest-neighbor algorithm, matching each patient in the R-NSM group to up to five controls without replacement. RESULTS:Before matching, the R-NSM group more frequently had hormone receptor-positive/human epidermal growth factor receptor 2-negative tumors, lower Ki-67 indices, and no neoadjuvant chemotherapy. After propensity score matching, most clinicopathologic variables were well balanced between groups. During a median follow-up of 37.5 months for R-NSM and 42.6 months for C-NSM, no locoregional recurrence, distant metastasis, or death occurred in the R-NSM group, whereas all seven recurrences (3.5%) occurred in the C-NSM group. Kaplan-Meier analysis showed no significant differences in locoregional recurrence-free survival, distant metastasis-free survival, or disease-free survival between groups, although all observed oncologic events occurred in the C-NSM group. CONCLUSION:R-NSM demonstrated oncologic outcomes comparable to those of C-NSM, with no recurrence or mortality despite a sufficiently long follow-up. These findings support R-NSM as a feasible and oncologically sound surgical option for appropriately selected patients with early-stage breast cancer.

BACKGROUND:The NAUTILUS trial randomized cT1-2/N0 breast cancer patients to evaluate the non-inferiority of omitting SLNB. We report the clinicopathologic characteristics and axillary lymph node (ALN) status of the patients enrolled in the NAUTILUS trial and suggest expectations based on the results of this trial, which are relevant in the context of the SOUND and INSEMA trials, where the majority of participants were aged 50 years or older. METHODS:The NAUTILUS trial randomized 1734 subjects into SLNB or no-SLNB arms. Axillary ultrasonography was mandatory to determine clinical N0. Clinicopathologic variables and ALN status in the SLNB arm were analyzed to determine expectations for the NAUTILUS trial results compared to other clinical trials. RESULTS:Among 1734 patients, 1664 subjects were available for clinicopathologic analysis; 50.4% were in the SLNB arm and 49.6% were in the no-SLNB arm. Median age was 55 (range, 29-92) years, and 40.1% were premenopausal. Overall, 1.7%, 83.9%, and 14.0% subjects were pTmic, pT1, and pT2, respectively, with a median tumor size of 1.3 cm (range, 0.1-6.0). In the SLNB arm, 11.2% had ALN metastasis, comprising 1.1%, 9.4%, and 0.6% with pN1mic, pN1, and pN2-3, respectively. ALN metastasis rates according to tumor size were 7.0%, 12.8%, and 17.2% for sizes ≤1.0 cm, >1.0 cm & ≤ 2.0 cm, and >2.0 cm & ≤ 5.0 cm, respectively. CONCLUSIONS:The NAUTILUS trial completed enrollment, with included 14.0% pT2 and 40.1% premenopausal subjects and is expected to show the impact of SLNB omission in these subgroups. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04303715.

Extracellular vesicle-derived mRNAs (EV-mRNAs) are emerging analytes for liquid biopsy research, but their reliable detection is limited by low RNA abundance and co-isolated nucleic acids. We compared five EV isolation approaches to identify a suitable workflow for EV-mRNA profiling using the NanoString nCounter platform in breast cancer. EV preparations from pooled plasma were evaluated for particle yield, RNA recovery, and transcript detection using the nCounter Breast Cancer 360 panel with pre-amplification. RNase A pretreatment and post-extraction DNase I treatment were used to assess extra-vesicular RNA and residual DNA contributions. DNase I treatment markedly reduced total counts and detected transcripts, highlighting the importance of minimizing residual DNA-derived signals in pre-amplified EV-mRNA analysis. Among the tested approaches, miRCURY (MIR) retained the highest number of detected transcripts after nuclease treatment and was selected for downstream profiling. This workflow was applied to plasma samples from healthy donors (n = 36), breast cancer patients without recurrence (n = 36), and breast cancer patients with recurrence (n = 31), followed by RT-qPCR assessment in an independent cohort. CCL5 and HIST1H3H were identified as exploratory breast cancer-associated EV-mRNA candidates, with CCL5 also showing a recurrence-associated pattern. These findings support MIR-based isolation with DNase I treatment as a practical workflow for NanoString-based EV-mRNA profiling in clinical plasma samples.

BACKGROUND:Perceived financial toxicity (FT) is an increasingly recognized concern among cancer survivors. However, its association with long-term oncologic outcomes, particularly after completion of active treatment, remains underexplored. METHODS:We conducted a prospective cohort study of 4163 breast cancer survivors from a tertiary cancer center in South Korea. Eligible participants were within 18 months of diagnosis, had completed surgery and any adjuvant chemotherapy or radiotherapy, and had no evidence of recurrence at enrollment. Perceived FT was assessed using the Comprehensive Score for Financial Toxicity (COST) questionnaire. FT was defined by a COST score <26. Primary outcome was recurrence-free survival (RFS), and secondary outcomes included all-cause mortality and quality-of-life (QoL) domains. Multivariable Cox proportional hazard models adjusted for age, stage, treatment, and socioeconomic factors. RESULTS:Among the cohort, 2109 (50.7 %) patients reported perceived FT after active treatment. FT was independently associated with increased risk of recurrence or death (HR 1.42, 95 % CI 1.08-1.87), and higher all-cause mortality (HR 1.74, 95 % CI 1.02-2.97). FT was also associated with significantly worse emotional functioning, social functioning, and future outlook. CONCLUSIONS:Perceived financial toxicity following active breast cancer treatment was associated with worse oncologic and quality-of-life outcomes, regardless of objective socioeconomic status. These findings underscore the need for routine assessment of perceived financial burden during survivorship care and targeted financial interventions, even in patients without traditionally defined financial vulnerability.

Objective: Accurate prediction of breast cancer (BC) recurrence after curative treatment is essential for optimizing surveillance strategies and personalized patient management. We aimed to prospectively validate a previously developed artificial intelligence (AI)–based BC recurrence prediction model in a real-world clinical setting.Methods: This prospective validation study included BC patients who underwent curative surgery followed by adjuvant therapy at a tertiary cancer center. The AI model integrated clinicopathologic variables and longitudinal follow-up data, including laboratory and imaging findings, to estimate individualized 2-year recurrence risk. Patients were stratified into low- and high-risk groups based on a predefined risk threshold. Model performance was evaluated using recurrence outcomes during follow-up.Results: Of 829 patients initially identified, 529 met eligibility criteria, and 400 were randomly selected. Among them, 391 were classified as low-risk and 9 as high-risk. Significant differences in clinicopathologic factors (T/N stage, ER, PR, HER2, Ki-67) were observed between groups, excluding age, adjuvant radiotherapy, and targeted therapy. During follow-up, 7 patients (1.8%) experienced recurrence, 6 in the low-risk group (1.5%) and 1 in the high-risk group (11.1%).Conclusion: This prospective validation demonstrates that the AI-based model can effectively identify BC patients at low risk of recurrence in a real-world clinical setting. The model shows potential as a clinical decision support tool to guide individualized surveillance strategies, although further multi-center studies with larger high-risk populations are warranted to enhance sensitivity and generalizability.

Axillary surgery in breast cancer has progressively shifted from radical clearance to selective de-escalation. Sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as the standard, markedly reducing morbidity while maintaining oncologic safety. More recently, randomized trials have challenged even the necessity of SLNB in certain patients, reflecting a broader movement toward optimization rather than maximal intervention. Evidence can be grouped according to the burden of sentinel node metastasis. Micrometastasis-focused trials (IBCSG 23-01, AATRM) showed that omission of ALND in patients with one or more micrometastases (≤ 2 mm) did not compromise survival or locoregional control. Mixed-burden trials (ACOSOG Z0011, AMAROS) included patients with 1-2 positive sentinel lymph nodes, regardless of micrometastatic or macrometastatic size, and confirmed the safety of avoiding ALND when appropriate systemic therapy and radiotherapy are given. Macrometastasis trials (SENOMAC, SINODAR-ONE, POSNOC) extended these findings to patients with 1-2 macrometastases (≥ 2 mm), demonstrating that ALND omission is still safe even in higher-burden disease. In parallel, de-escalation has advanced further. SOUND and INSEMA established non-inferiority of observation vs. SLNB in clinically node-negative (cN0), imaging-negative tumors, while ongoing studies such as NAUTILUS are validating these results in Asian populations. In the neoadjuvant setting, SLNB is standard for cN0 patients and feasible in clinically node-positive patients who convert to cN0 after neoadjuvant chemotherapy. Ongoing trials (ASICS, EUBREAST-01, ASLAN) are exploring whether axillary surgery can be omitted entirely in excellent responders, particularly in human epidermal growth factor receptor 2-positive and triple-negative breast cancer. The collective data indicate a clear trend. Axillary surgery should be optimized to disease biology, systemic therapy response, and patient quality of life.

BACKGROUND:Evidence to guide (neo)adjuvant chemotherapy choices in carriers of germline BRCA1/BRCA2 pathogenic variants (BRCA carriers) with early breast cancer (BC) is limited. We evaluated the association of different chemotherapy regimens with survival outcomes in this population. METHODS:The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, retrospective cohort study of BRCA carriers diagnosed with stage I-III BC at age ≤ 40 years, between 2000 and 2020. Disease-free survival (DFS) and overall survival (OS) were assessed among patients with HER2-negative disease treated with anthracycline-taxane, anthracycline-no-taxane, or non-anthracycline (neo)adjuvant chemotherapy. The association of platinum use with outcomes was evaluated in triple-negative breast cancer (TNBC). RESULTS:Among 4200 young BRCA carriers from 109 centres who received (neo)adjuvant chemotherapy for HER2-negative BC, 58.7% had TNBC. Median follow-up was 8.1 years (IQR, 4.7-12.6 years). Anthracycline-taxane, anthracycline-no-taxane, and non-anthracycline regimens were used in 74.4%, 19.3%, and 6.3% of patients, respectively. Platinum agents were administered in 19.8% of TNBC cases. After multivariable adjustment, no significant differences in DFS or OS were observed between anthracycline-no-taxane and anthracycline-taxane regimens (DFS adjusted hazard ratio [aHR] 0.88, 95% CI 0.73-1.05; OS aHR 1.20, 95% CI 0.87-1.67) or non-anthracycline regimens (DFS aHR 1.07, 95% CI 0.82-1.38; OS aHR 1.16, 95% CI 0.68-2.0). In TNBC, platinum use was not associated with improved outcomes. CONCLUSIONS:In young BRCA carriers with HER2-negative early BC, no statistically significant differences in survival outcomes were detected across different chemotherapy regimens. Our findings may inform future prospective studies evaluating chemotherapy de-escalation strategies in this genetically defined population.

Breast cancer incidence is increasing worldwide, leading to a growing population of survivors and raising questions about optimal surveillance strategies. Current guidelines do not recommend routine imaging for asymptomatic breast cancer survivors, yet advances in diagnostic technologies may enable earlier detection of distant metastases and potentially improve outcomes. The aim of this study was to evaluate the association between symptom status at the time of distant metastasis detection and post-metastasis overall survival in breast cancer patients. We retrospectively reviewed 7,840 women who underwent surgery for primary breast cancer at Samsung Medical Center between 2010 and 2014 and identified 316 patients who subsequently developed distant metastases. Patients were classified as asymptomatic (n = 204, 64.6

PURPOSE:Young patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors often exhibit poor outcomes. This study evaluated whether BRCA mutation contributes to prognosis by comparing oncologic outcomes according to BRCA status. MATERIALS AND METHODS:We conducted a retrospective study of a prospective institutional cohort. Among 1,025 patients 40 years and younger with ER-positive, HER2-negative breast cancer who underwent BRCA1/2 testing, 967 patients were included (excluding low ER expression). Ninety-eight patients (10.1%) were BRCA mutation carriers. Propensity score matching (1:4) and multivariate Cox regression were performed using covariates differing between groups. RESULTS:BRCA mutation carriers showed more aggressive features. They had worse distant metastasis-free survival (DMFS) compared with noncarriers (hazard ratio [HR], 2.40, P < .001), with a greater risk in late DMFS beyond 5 years (HR, 3.50, P < .001). These findings persisted after adjustment (DMFS HR, 1.76, P = .038, late DMFS HR, 2.84, P = .009). Overall survival was not significantly different. Bone was the most common first site of metastasis in BRCA carriers, whereas noncarriers more frequently showed metastasis to multiple sites. In exploratory subgroup analysis, luminal A-like BRCA carriers consistently showed the poorest survival among the four subgroups. CONCLUSION:In luminal-type YBC excluding low ER expression, BRCA carriers demonstrated more aggressive features and significantly worse distant metastasis outcomes. These findings support the need for long-term surveillance and consideration of tailored treatment strategies, including PARP inhibitors, in this high-risk population.

The clinical significance of residual mammographic microcalcifications after neoadjuvant systemic therapy in human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer remains unclear. Traditionally, persistent calcifications have prompted wide excisions or mastectomies under the assumption that they indicate residual disease. However, accumulating evidence suggests that calcifications may persist as treatmentrelated or biologically-attenuated changes, rather than as viable carcinomas, particularly in the era of dual HER2-directed therapy. Recent Korean studies demonstrate that patients with favorable radiologic response who achieve pathologic complete response maintain excellent local control after breast-conserving surgery, even when residual calcifications are present. A large multicenter cohort study reported a 5-year local recurrence-free survival rate of 97.4% and a validated prediction model showed strong discriminatory performance. This Brief Communication synthesizes emerging evidence on the biological basis and clinical implications of residual calcifications after neoadjuvant therapy, with emphasis on recent Korean data. Current evidence supports a response-adapted surgical approach in selected patients, emphasizing clip-guided excision of the invasive index lesion and consistent delivery of whole-breast irradiation rather than routine removal of the entire pretreatment calcification field in patients with HER2+ breast cancer. Prospective validation with a longterm follow-up is warranted to further refine patient selection and confirm the safety of this strategy in clinical practice.

BACKGROUND:In patients with hormone receptor (HR)-positive early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). In this article, we report updated results from a preplanned analysis with 2.5 years of additional follow-up. PATIENTS AND METHODS:POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18-30 months and for up to 2 years) to attempt pregnancy in young patients with BC, enrolled 518 eligible women (≤42 years of age, stage I-III BC, desiring pregnancy) from December 2014 to December 2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were compared with those of the SOFT/TEXT trials as external controls. RESULTS:At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT [-0.9% difference, 95% confidence interval (CI) -4.2% to 2.6%]. The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively (-2.1% difference, 95% CI -4.5% to 0.4%). Among 497 women followed for nondisease outcomes, 377 (76%) had ≥1 documented pregnancy on trial, and 343 of 497 (69%) had ≥1 live birth, totaling 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation with those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI 9.6% to 20.2%) and 11.5% (95% CI 8.4% to 15.7%), respectively. CONCLUSION:Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy, including use of fertility preservation, does not increase the risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.

BackgroundEndocrine therapy (ETx) for hormone receptor–positive breast cancer frequently induces menopausal symptoms that may compromise treatment adherence. However, longitudinal symptom trajectories compared with natural menopausal progression remain unclear.MethodsThis longitudinal cohort study included 5,734 women from two prospective cohorts. Menopausal symptoms were assessed using the Menopause Rating Scale (MRS). Women with breast cancer (n=2,583) were recruited from the Breast Cancer Information Grand Round for Survivorship cohort, and women without breast cancer (n=3,151) from the Kangbuk Samsung Health Study. Linear mixed-effects models estimated longitudinal changes in MRS scores according to breast cancer status, menopausal status, and ETx use. Difference-in-differences (DiD) analyses used premenopausal women without breast cancer as the reference group.ResultsAmong premenopausal women, ETx was associated with greater increases in total MRS scores compared with women without breast cancer (DiD 3.30; 95% CI, 2.04–4.58 at 1 year). Premenopausal women receiving ETx experienced sustained symptom increases over 3 years, particularly those receiving ovarian function suppression. Regimens including gonadotropin-releasing hormone agonists were associated with the greatest increases in symptom burden. Among postmenopausal women, ETx was associated with modest changes in total MRS scores but a significant increase in urogenital symptoms (DiD 0.71; 95% CI, 0.26–1.16).ConclusionsETx for breast cancer is associated with sustained increases in menopausal symptoms beyond those observed during natural menopause. The excess symptom burden is most pronounced among premenopausal women receiving ovarian function suppression. These findings highlight the importance of proactive symptom monitoring and supportive care strategies to improve long-term adherence to endocrine therapy.

This study aimed to identify prognostic factors and to stratify recurrence risk using a prognostic model incorporating the identified factors in patients with residual triple-negative breast cancer (TNBC) following neoadjuvant systemic therapy (NST). A retrospective analysis was conducted using data from a prospectively collected single-institution database. Eligible patients had residual TNBC after NST and curative surgery between 2007 and 2020 and completed planned postoperative radiotherapy. Prognostic factors for disease-free survival (DFS) were identified using multivariable Cox proportional hazards regression. Risk groups were stratified according to the number of these factors. A total of 347 patients were included. With a median follow-up of 61.6 months, the 5-year DFS and overall survival rates were 62.5

Background and purposeRecent trials have demonstrated the safety of sentinel lymph node biopsy (SLNB) omission in selected patients with early breast cancer. However, criteria for identifying patients suitable for partial breast irradiation (PBI) without surgical axillary evaluation remain undefined. This study aimed to identify the candidates for PBI in pT1 breast cancer patients.Materials and methodsA retrospective analysis was conducted on 5,097 patients with pT1 breast cancer who underwent breast surgery with axillary evaluation between 2016 and 2020. All patients had clinically node-negative disease (cN0) confirmed by preoperative axillary ultrasound. Univariable and multivariable logistic regression analyses were used to identify independent predictors of axillary lymph node metastasis (ALNM).ResultsThe overall ALNM rate was 13.9% (708/5,097). The mean age was 51.3 years. Multivariable analysis identified lymphovascular invasion (LVI) as the strongest independent predictor (odds ratio [OR] 5.57, 95% confidence interval [CI] 4.61–6.74, p < 0.001), and LVI-positive patients (14.3%) had a 42.1% ALNM rate. pT1c stage was also a significant independent predictor (OR 2.13, 95% CI 1.71–2.65, p < 0.001). A simple classification using LVI and tumor size stratified patients into three groups: low-risk (LVI-negative, tumor ≤1.0 cm; 40.1% of patients), intermediate-risk (LVI-negative, tumor >1.0 cm; 45.7%), and high-risk (LVI-positive; 14.3%). The corresponding ALNM rate was 4.9%, 13.0%, and 42.1%, respectively.ConclusionsPatients with pT1a-b tumors without LVI represent a low-risk population with an axillary metastasis rate below 5%. These findings suggest the feasibility of PBI in this low-risk subgroup without SLNB, warranting validation through prospective randomized trials.

PURPOSE:Long-term outcome comparisons between invasive lobular carcinoma (ILC) and invasive carcinoma of no special type (NST, historically referred to as invasive ductal carcinoma) remain inconsistent, particularly in patients with low-proliferative hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease. This study evaluated the long-term outcomes of ILC and NST in a pathologically defined, low-proliferative, HR+/HER2- (luminal A-like) cohort. METHODS:This retrospective, single-institution study included patients with HR+/HER2- breast cancer and Ki-67 ≤ 20% who underwent surgery between 2008 and 2015. Patients with mixed histopathology, those who underwent palliative surgery, or those who received neoadjuvant chemotherapy were excluded. Survival was analyzed using the Kaplan-Meier method and multivariable Cox regression. A secondary 24-month landmark analysis included patients who were alive, disease-free, under observation, and receiving endocrine therapy 24 months after surgery. RESULTS:Among 3,439 patients, 3,156 had NST and 283 had ILC. Compared with NST, ILC was associated with a higher rate of synchronous bilateral breast cancer, a more advanced pathological stage, and a lower nuclear grade. In the comprehensive cohort, breast cancer-specific survival did not differ significantly (log-rank p = 0.081), whereas disease-free survival (DFS) and distant metastasis-free survival (DMFS) were worse in patients with ILC (log-rank p < 0.001 and p = 0.005, respectively). After adjustment for measured clinicopathological factors, these differences were no longer statistically significant (DFS: adjusted hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.91-1.79; p = 0.164; DMFS: adjusted HR, 1.38; 95% CI, 0.83-2.30; p = 0.210). Detailed biomarker analyses showed similarly high estrogen receptor expression in both groups and lower exact Ki-67 values in ILC. The 24-month landmark analysis revealed the same overall pattern. CONCLUSION:In this low-proliferative HR+/HER2- cohort, ILC showed less favorable unadjusted long-term DFS and DMFS than NST, but these differences were attenuated and were no longer statistically significant after adjustment for measured clinicopathological characteristics.

PURPOSE:While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. METHODS:Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS:Independent predictors of pCR included PR-negative status, positivity for basal-like markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. CONCLUSION:This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediate-scores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

BACKGROUND:Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally have favorable outcomes. However, in the hormone receptor-positive/HER2-positive (HR+/HER2+) subtype, prognostic heterogeneity may persist even after pCR. In particular, the role of gonadotropin-releasing hormone agonist (GnRHa) for ovarian function suppression in premenopausal patients remains unclear. We aimed to identify prognostic factors and evaluate the clinical impact of GnRHa in this population. METHODS:We performed a retrospective analysis of prospectively collected cohorts from Samsung Medical Center and Asan Medical Center. A total of 332 premenopausal patients with HR+/HER2+ breast cancer who achieved pCR after anti-HER2 containing NAC (2008 - 2021) were included. Patients were categorized according to GnRHa use during adjuvant endocrine therapy. The primary endpoints were disease-free survival (DFS) and distant metastasis-free survival (DMFS), analyzed using Cox proportional hazards regression and the Kaplan-Meier method. RESULTS:Among 332 patients, 218 (65.7%) did not receive GnRHa and 114 (34.3%) did. With a median follow-up of 65.8 months, clinical nodal stage (cN3) was identified as an independent adverse prognostic factor for both DFS (HR 5.92, p < 0.001) and DMFS (HR 13.60, p < 0.001). In contrast, GnRHa use was not significantly associated with survival outcomes. Patients with cN3 disease showed significantly worse outcomes than those with cN0-2 (5-year DFS: 80.0%% vs 96.2%; DMFS: 87.5% vs 97.9%). No clear survival differences were observed according to GnRHa use. Subgroup analyses showed no significant association between GnRHa and survival, although a trend toward improved outcomes was observed in the cN3 subgroup. CONCLUSION:Prognostic heterogeneity persists among premenopausal HR+/HER2+ patients achieving pCR, with baseline nodal status as a key determinant of outcomes. GnRHa was not associated with improved survival overall, although a potential benefit in high-risk subgroups cannot be excluded. These findings support a risk-adapted approach to adjuvant endocrine therapy rather than uniform intensification.