Journal of Breast Cancer最新文献

Women carrying pathogenic/likely pathogenic variants of high- or moderate-penetrance genes, such as BRCA1/2, TP53, PTEN, PALB2, CDH1, STK11, CHEK2, and ATM, face markedly elevated lifetime risks of breast cancer. Risk-reducing mastectomy (RRM) reduces incidence by approximately 90% as shown in large observational cohort studies and meta-analyses. However, the survival advantage of RRM remains uncertain given the observational design, heterogeneous population, and the lack of randomized controlled trials. For moderate-penetrance genes, guidance relies more on absolute risk modeling and expert consensus than on direct outcome data. Hence, RRM is recognized as an option for women at high-risk, while emphasizing individualized, multidisciplinary decision-making that incorporates oncological, genetic, reconstructive, and psychosocial perspectives. In addition, choices are shaped by many factors, such as age, family plans, culture, and healthcare systems in real practice. This review integrates the current evidence and evolving guidelines to clarify the benefits, limitations, and controversies surrounding RRM. By addressing existing knowledge gaps and decision-making challenges, it aims to facilitate informed patient-centered counseling for the management of hereditary breast cancer.

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: While postmenopausal women with low recurrence scores in genomic assay may safely forgo adjuvant chemotherapy, the RxPONDER trial demonstrated that premenopausal women with 1-3 positive nodes (pN1) derive significant benefit from adjuvant chemotherapy regardless of low recurrence scores. The INTERSTELLAR trial is evaluating whether ovarian function suppression (OFS) combined with adjuvant endocrine therapy (ET) can offer comparable efficacy to chemotherapy in this specific patient population.

Methods: INTERSTELLAR is a prospective, multicenter, single-arm, non-inferiority cohort study enrolling premenopausal women aged ≤ 50 with pT1-2, estrogen receptor +/human epidermal growth factor receptor 2 -, pN1 breast cancer. Genomic risk is assessed using OncoFREE^®, a next-generation sequencing-based assay developed in the Republic of Korea. Patients classified as low genomic risk (Decision Index ≤ 20) receive OFS combined with either an aromatase inhibitor or tamoxifen for 5 years, while patients with high genomic risk receive standard adjuvant chemotherapy followed by ET. The primary endpoint is 5-year distant disease-free survival (DDFS). Non-inferiority will be established if the lower bound of the 97.5% one-sided confidence interval exceeds 93.1%, benchmarked against a historical control DDFS of 96.1% derived from the RxPONDER trial. The study plans to enroll 604 patients total, with a target of 380 evaluable low-risk patients after accounting for expected genomic risk distribution and study dropout rates.

Discussion: Our results may establish evidence supporting the omission of adjuvant chemotherapy in premenopausal women with low genomic risk scores and limited nodal involvement (p-N1), potentially reducing treatment-related morbidity while preserving comparable oncologic outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT05333328. Registered on April 18, 2022.

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.

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.

Purpose: The Charlson Comorbidity Index (CCI) is associated with the prognosis of patients with breast cancer. However, comorbidities are often confounded by both age and treatment course; therefore, it is essential to eliminate the influence of these factors. We analyzed the relationship between CCI scores and breast cancer prognosis using propensity score matching (PSM).

Methods: We retrospectively analyzed 1,403 patients with primary breast cancer who underwent curative surgery. After PSM, 764 patients were selected for analysis of clinicopathological and prognostic factors.

Results: After PSM, prognosis was compared between groups according to several CCI cutoff values. No significant differences in disease-free survival or breast cancer-specific overall survival (OS) were observed according to the CCI score. Similarly, no significant differences in OS were observed between the high- and low-CCI groups at CCI cutoff values of 1 and 2. However, at a CCI cutoff value of 3, OS was significantly worse in patients with higher CCI scores.

Conclusion: Among patients with breast cancer, those with CCI scores ≥ 3 often experience mortality due to diseases other than breast cancer.

Purpose: Relevant factors can have shifting prognostic impacts on cardiovascular disease (CVD) occurrences among in patients with breast cancer (BC) over time. CVD incidence and its driving factors vary among different CVDs. We examined the time to the first occurrence of heart attack, atrial fibrillation, embolic stroke, angina pectoris, embolism, peripheral vascular disease, and heart failure (HF). We particularly focused on the influence of molecular subtype, adjusting for age, tumor stage, and radiation therapy.

Methods: The 36,605 women diagnosed with BC from the Norwegian Cancer Registry were included. Cox regression analyses were performed for the first time for six CVDs, with death treated as a competing risk. The association between the time to first CVD diagnosis and the patient's molecular subtype was calculated. Because the Cox proportional hazard assumption was not met, a random survival forest (RSF) analysis was conducted.

Results: The association between the time to the first CVD and the patient's molecular subtype differed for each CVD and was non-linear for HF. The time-varying cardiovascular risk in human epidermal growth factor receptor 2 (HER2)-positive versus HER2-negative breast cancer patients reflects differences in treatment, biology, and patient profiles. HER2-positive patients face early cardiotoxicity due to targeted therapies and are closely monitored, while HER2-negative patients, often older with higher baseline CVD risk, may experience delayed detection due to less routine cardiac surveillance. In ranking the factors with respect to their predictive importance for time to first HF, molecular subtype emerged as the second most important factor, followed by age.

Conclusion: Time to HF depends on the molecular subtype in a time-dependent manner. RSF analyses can identify complex relationships between predictors and survival without the Cox proportional hazard assumption, providing important insights into how patient and treatment factors are associated with time to CVD.

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.

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.

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.