Journal of Breast Cancer最新文献

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype of breast cancer associated with poor clinical outcomes. Although programmed death ligand 1 (PD-L1) expression has emerged as both a prognostic and predictive biomarker, its utility remains limited, especially in PD-L1-negative tumors. The identification of additional molecular markers is crucial for improving prognostic stratification and guiding treatment strategies.

Methods: Formalin-fixed, paraffin-embedded tumor tissues from 38 patients with TNBC were analyzed. PD-L1 expression was assessed using immunohistochemistry and categorized as positive or negative. Whole-exome sequencing was performed, and somatic variants were analyzed using Maftools. Mutational signatures were compared with the Catalogue Of Somatic Mutations In Cancer reference profiles. Survival analyses were performed to evaluate the prognostic significance of the identified variants.

Results: Mutational landscape analysis revealed that C>T and G>A transitions were the most frequent base substitutions. PD-L1-negative tumors exhibited a predominance of single-base substitution (SBS) 5, whereas PD-L1-positive tumors resembled SBS6, reflecting potential differences in the underlying mutational processes. Comparative analysis identified 12 PD-L1-negative-specific and seven PD-L1-positive-specific variants. Among PD-L1-negative tumors, mutations in ANGPTL5 and KIAA1549L were significantly associated with worse overall survival.

Conclusions: Our findings highlight distinct mutational profiles and prognostic variants according to PD-L1 status in TNBC. ANGPTL5 and KIAA1549L variants may serve as potential prognostic markers for PD-L1-negative tumors. These results underscore the value of incorporating genomic information to refine the prognostic stratification of TNBC.

Purpose: Axillary surgery is increasingly omitted in patients with early-stage breast cancer undergoing upfront surgery, as supported by trials such as SOUND and INSEMA. However, in the neoadjuvant setting, the omission of axillary surgery has only been explored in small single-arm studies involving highly selected patients with confirmed breast pathologic complete response (pCR). The NeoNAUTILUS trial aimed to evaluate the oncologic safety of omitting sentinel lymph node biopsy (SLNB) in patients with a high probability of achieving an axillary pCR (ypN0) following neoadjuvant systemic therapy (NST), regardless of breast pCR status.

Methods: NeoNAUTILUS is a prospective, multicenter, randomized, controlled, non-inferiority trial conducted at 12 tertiary centers in Korea. Eligible participants were women with clinical T1-T3, N0, or selected N1 invasive breast cancer, who completed NST and were candidates for breast-conserving surgery (BCS). Prior to enrollment, all patients underwent axillary ultrasound after NST completion to exclude suspicious lymph nodes. Patients with clinical N0 disease of any subtype were eligible for inclusion. Patients with clinical N1 disease with human epidermal growth factor receptor 2-positive or triple-negative tumors may be included if their primary tumor demonstrates a > 30% reduction on magnetic resonance imaging after NST. Participants were randomized 1:1 to undergo BCS with or without SLNB, stratified by clinical nodal status and tumor subtype. Patients were randomized and remained blinded until surgery. The primary endpoint is the 5-year invasive disease-free survival. A total of 464 patients are expected to be enrolled over 3 years, with a 5-year follow-up period.

Discussion: NeoNAUTILUS is the first randomized trial to assess the omission of axillary surgery after NST based on the predicted nodal response, independent of breast pCR. This study may redefine axillary management in the neoadjuvant setting by identifying patients who can safely avoid SLNB, thereby reducing surgical morbidity without compromising oncologic outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT06704945. Registered on November 26, 2024. Clinical Research Information Service Identifier: KCT0010174. Registered on February 7, 2025.

Purpose: Breast-conserving surgery (BCS) with whole-breast radiation therapy is the standard treatment for invasive breast cancer, with surgical margin status crucial for minimizing ipsilateral breast tumor recurrence (IBTR). This study aimed to reassess IBTR, considering breast's three-dimensional structure and the unclear significance of superior and deep margins.

Methods: We analyzed 3,712 patients who underwent BCS at Samsung Medical Center (2011-2015), excluding those with metastatic disease, neoadjuvant chemotherapy, bilateral cancer, or benign tumors. IBTR was defined using two criteria: 1) 90-degree angle (IBTR⁹⁰), and 2) 120-degree angle (IBTR¹²⁰), based on the directional location of recurrence relative to the original tumor site. Margin status was evaluated by resection distance and categorized as positive, close (less than 1 mm, excluding positive margins), 1 mm, 2 mm, or > 2 mm.

Results: This study included 3,712 patients, with a median follow-up of 101 months. Local and distant recurrences occurred in 89 of 3,712 (2.4%) and 101 of 3,712 (2.7%) patients. Using the IBTR⁹⁰ definition, the IBTR rate was the highest in the close margin group (7/219, 3.2%) and increased to 4.6% (11/238) with the 120-degree angle definition. A statistically significant difference in IBTR¹²⁰ rates was observed between margin positive or close margin cases (3.5%) and other margin statuses (1.8%) when superficial and deep margins were excluded (p = 0.042). Notably, the IBTR rate for positive margins was lower than that for close margins in both the IBTR⁹⁰ (1.0% vs. 3.2%) and IBTR¹²⁰ (1.0% vs. 4.6%) analyses when superficial and deep margins were excluded.

Conclusion: IBTR rates were higher in close and positive margin groups under the 120-degree definition, particularly when superficial and deep margins were excluded. Although positive margins did not always show the highest recurrence, margin status still influenced IBTR risk. Re-excision should be individualized based on imaging, pathology, and clinical judgment.

Purpose: The nipple-areola complex (NAC) is generally resected to treat breast cancer in or near the nipple-areola (NA) region. Embryologically, each glandular lobe system is independent until the ductal opening on the nipple surface. Thus, the nipple can be preserved by partial excision, including the collecting duct occupied by the intraductal extension of breast cancer. We aimed to demonstrate that NAC preservation by partial NA excision is feasible in early-stage breast cancer with intraductal extension into the NA region.

Methods: The participants in this surgery were patients with breast cancer in stages 0-IIA who were classified into the following three groups. Space-occupying lesions were defined as primary lesions. The main lesion was located outside the NA region, accompanied by intraductal extension within the NA region (39 patients). The main lesion partially extended to the subareolar area and was accompanied by intraductal extension within the NA region (13 patients). The main lesion partially extended to the subareolar area but was not accompanied by intraductal extension within the NA region (four patients). The degree of intraductal extension toward the nipple was determined using preoperative contrast-enhanced magnetic resonance imaging with the patient in the prone position. Diagnoses were based on the pathological results of the postoperative resection specimens. Breast-conserving surgery was performed via quadrantectomy of the nipple and the region under the nipple, with the addition of full-layer excision of the areolar region, including the target duct, and further resection, including the main lesion.

Results: The excised portion resembled an entire cake-cut. Four patients had positive resection margins in the NA region. Postoperative pathological examination revealed no intraductal extension under NAC in eight patients. Deformation of the NAC was minor.

Conclusion: This approach may be suitable for NAC-sparing procedures.

Purpose: Surveillance guidelines following breast cancer surgery recommend mammography as the sole imaging modality. However, the accuracy of mammography is low in younger women and in those with dense breast tissue. Additional imaging modalities, such as ultrasonography and magnetic resonance imaging (MRI), may offer diagnostic benefits. This prospective, multicenter study (KBCSG-27) aims to compare the diagnostic performances of mammography, ultrasonography, and MRI for detecting second breast cancer (SBC) in women with a personal history of breast cancer (PHBC) and dense breasts.

Methods: This study will recruit approximately 1,756 women, aged 20-75 years, who were treated for stage 0-III breast cancer and have dense breast tissue on mammography. Participants will undergo two annual breast screenings, each consisting of mammography, ultrasonography, and MRI. MRI will be performed using either abbreviated magnetic resonance imaging (AB-MRI) or full-protocol magnetic resonance imaging (FP-MRI), which will be randomly assigned such that each participant receives both protocols alternately. Radiologists will independently interpret all images. A combination of pathology results and 12-month follow-up will serve as the reference standard. A patient-reported outcome (PRO) tool will be used to assess patients' experiences and preferences between AB-MRI and FP-MRI. The primary objective is to compare the cancer detection rates of ultrasonography versus AB-MRI and ultrasonography versus FP-MRI. Secondary outcomes include comparisons of the invasive cancer detection rates, abnormal interpretation rates, sensitivity, specificity, positive and negative predictive values, accuracy, and interval cancer rates. Subgroup analyses will be conducted based on age, menopausal status, mammographic breast density, and molecular subtype. Additionally, PRO results of AB-MRI and FP-MRI will be compared.

Discussion: This ongoing, prospective, multicenter study aims to evaluate the performance of ultrasonography, AB-MRI, and FP-MRI in SBC surveillance in women with PHBC and dense breasts. Enrollment is expected to be completed by 2025, with results anticipated after 2028.

Trial registration: ClinicalTrials.gov Identifier: NCT05797545. Registered on April 23, 2023.

Purpose: Evaluating the role of preoperative axillary ultrasound (US) in early-stage, clinically node-negative breast cancer, focusing on its ability to predict nodal metastasis and long-term recurrence.

Methods: This retrospective study included patients with T1-T2 clinically node-negative breast cancer who underwent preoperative axillary US and surgery between January and December 2009. Based on US findings, patients were classified as US-positive (presence of suspicious nodes, such as cortical thickening or absent fatty hilum) or US-negative. Clinicopathological features and recurrence outcomes were analyzed using the χ² test, Cox proportional hazards regression, and Kaplan-Meier survival analysis.

Results: Among 878 women (mean age, 49 ± 9 years), 234 were US-positive and 644 were US-negative; 283 patients were pathologic node-positive (pN ≥ 1) and 595 were node-negative (pN0). Preoperative axillary US demonstrated a sensitivity of 42.4% (95% confidence interval [CI], 36.8-48.2); specificity, 80.8% (95% CI, 77.5-83.8); positive predictive value, 51.3% (95% CI, 44.9-57.6); and negative predictive value, 74.7% (95% CI, 71.2-77.9). The US-positive group had a higher rate of axillary lymph node dissection (62.8% vs. 32.8%), greater mean number of metastatic nodes (2.6 vs. 0.5), and higher proportion of macrometastasis (94.2% vs. 71.8%) compared with the US-negative group (all p < 0.001). The 10-year recurrence-free survival was lowest in the pN-positive/US-positive group (90.3%; 95% CI, 82.7-94.7), intermediate in the pN-positive/US-negative group (92.4%; 95% CI, 86.7-95.7), and highest in the pN-negative group (97.4%; 95% CI, 95.4-98.5) (log-rank p < 0.001).

Conclusion: Preoperative axillary US might help assess lymph node metastasis in clinically node-negative patients. Moreover, US positivity was associated with an increased risk of long-term recurrence.

Phyllodes tumors (PTs) are biphasic fibroepithelial lesions. Approximately 20% of malignant PTs metastasize hematogenously, most commonly to the lungs and bones. Treatment of metastatic PT is challenging because of its rarity. A 39-year-old woman with a left humeral fracture was admitted to our hospital. She had been diagnosed with breast PT a year prior, and humeral bone tissue pathology showed a metastatic PT similar to her breast PT. The patient received systemic high-dose chemotherapy, including etoposide, ifosfamide, and cisplatin, concurrently combined with radiotherapy to facilitate remission, after which the remnant tumor was removed. After achieving complete remission, the patient received chemotherapy with doxorubicin and cisplatin as adjuvants. To the best of our knowledge, this is the first report of a metastatic PT in which complete remission was achieved with high-dose chemotherapy combined with radiotherapy, followed by surgical resection and adjuvant chemotherapy.

Purpose: Profilin 1 (Pfn1) has been implicated in cytoskeletal regulation; however, its role in breast cancer progression and DNA replication remains unclear. This study investigated the functional significance of Pfn1 nuclear-cytoplasmic shuttling in breast cancer.

Methods: We analyzed Pfn1 expression and its correlation with DNA replication, repair, and oncogenic markers in breast cancer cell lines. Chromatin-bound and soluble Pfn1 levels were quantified by western blotting. The effects of nuclear (nuclear localization sequence-Pfn1) and cytoplasmic (nuclear export sequence-Pfn1) localization on cell growth, DNA replication, and stemness were assessed using colony formation, Alamar blue fluorescence, replication protein A 32-kDa foci staining, and DNA fiber assays. Mouse xenografts of breast cancer cells were used to determine the effect of Pfn1 localization on tumor growth in vivo. We identified the direct interactors of nuclear Pfn1 by immunoprecipitation, and their affinity was determined using bio-layer interferometry.

Results: Pfn1 expression was positively correlated with DNA replication, repair, p53, and MYC expression. Chromatin-bound Pfn1 was significantly degraded in breast cancer cell lines compared to that in non-cancerous MCF10a cells. Nuclear Pfn1 inhibited cell growth and DNA replication in SKBR3 cells, while cytoplasmic Pfn1 promoted cell survival and DNA replication in MCF10a cells. Loss of nuclear Pfn1 in SKBR3 cells inhibited their growth in vivo. Additionally, cytoplasmic Pfn1 upregulated stemness markers (c-Myc, B lymphoma Mo-MLV insertion region 1, and Nijmegen breakage syndrome 1). Pfn1 regulated cell stemness by binding to the nucleosome remodeler sucrose non-fermenting 2 homolog.

Conclusion: Our findings revealed that nuclear Pfn1 acts as a tumor suppressor by inhibiting DNA replication and cell growth, while cytoplasmic Pfn1 promotes tumorigenesis by enhancing stemness and replication efficiency. These results highlight the dual role of Pfn1 in breast cancer progression, governed by its subcellular localization. They suggested that modulating Pfn1 nuclear-cytoplasmic shuttling may be a potential therapeutic strategy.

Artificial intelligence (AI) is used in various areas of radiology, particularly in breast imaging, starting with mammography and extending to ultrasonography (US) and magnetic resonance imaging (MRI). This overview aims to examine the introduction, applications, and challenges of AI in breast imaging. This narrative outlines the applications of AI in various modalities-including mammography, US, and MRI-and discusses its indications, ongoing challenges, and future perspectives. AI has been used for identification, classification, detection, diagnosis, breast density assessment, treatment response, and prediction of prognosis. AI can help radiologists avoid missed diagnoses due to heavy workloads and enhance workflow efficiency. The integration of AI software into daily practice, along with further validation and refinement, is necessary to support radiologists' workflows.

We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) change after the first cycle of palliative chemotherapy can be a prognostic indicator in de novo stage IV breast cancer. We retrospectively reviewed 218 patients treated between January 1997 and December 2012 at Asan Medical Center, Seoul, Korea. The NLR change (ΔNLR = NLR after first cycle of chemo - initial NLR [iNLR]) was significantly inversely associated with breast cancer specific survival (BCSS) (p = 0.031). The 1-, 3-, and 5-year BCSS rates of patients in the increased NLR group were 78.4%, 37.8%, and 25.7%, and 88.9%, 55.6%, and 35.4%, respectively, in the other group (p = 0.035, 0.014, and 0.043, respectively). Multivariate analysis suggested that NLR was an independent prognostic factor (hazard ratio [HR], 1.748; 95% confidence interval [CI], 1.084-2.818). When patients were divided into four groups combining iNLR and ΔNLR, patients in high iNLR & increased NLR group (HR, 4.294; 95% CI, 1.586-11.629) had worst prognosis compared to patients in low iNLR & stationary or decreased NLR groups.