Breast Cancer最新文献

Background: There is no comprehensive report regarding which patient groups were disrupted by the COVID-19 pandemic in Japan having universal health insurance system. To provide the guidance regarding how to act in future pandemics, we investigated the changes in breast cancer (BC) diagnosis and treatment during the COVID-19 pandemic.

Methods: The trends of monthly data were calculated in relation to the variables of a total of 291,018 primary BCs registered on the Japanese National Clinical Database between January 2018 and April 2021.

Results: An analysis of the nationwide data during the pandemic showed 9% decrease of newly identified BC compared with before the pandemic. The impact was more relevant in the 40-50, 51-60 and 61-70-years age groups (13%, 8% and 9% decrease, respectively). The most substantial reduction was noted in patients identified through screenings without symptoms with a 17% decrease. These effects were also apparent in cT1, cN0, cStage 0, and cStage I (11%, 9%, 8% and 11% decrease, respectively). In breast surgery procedures, there was a notable decrease in breast-conserving surgery (13%) as well as post-operative radiation therapy (11%). During this period, strategies using neoadjuvant endocrine therapy or chemotherapy were implemented to avoid treatment delays for especially Stage I patients (1.5 folds increase).

Conclusions: We have identified the patient groups that are more vulnerable to the effects of the pandemic. The changes during the pandemic might provide the guidance regarding how to act in future emergencies to minimize disadvantages for BC patients.

Background: Estrogen receptor (ER) expression is critical in breast cancer treatment. While low ER (1-9%) resembles triple-negative cancer with chemotherapy efficacy, the significance of "intermediate expression" (≥ 10%) and the therapeutic efficacy remain unclear. This study explores the differences in staining patterns and molecular characteristics of ER-low to intermediate expression to guide treatment.

Methods: A total of 104 breast cancer patients treated between January 2008 and July 2024 with an Allred Proportion Score (PS) of 2-4 were included. PS2 (n = 21) was classified as ER-low, while PS3 (n = 26) and PS4 (n = 57) as ER-intermediate (ER-int). ER-int was further divided by ER staining pattern: "Island" (heterogeneous) and "Scatter," (uniform) subgroups. The prognosis, clinical factors, and gene expression profiles (n = 11) were analyzed.

Results: The Island subgroup was associated with poorest prognosis (p = 0.0116), particularly among the patients treated with endocrine-only treatment patients (p < 0.0001). Elevated tumor-infiltrating lymphocyte (TIL) levels correlated with worse prognosis in endocrine-only treatment patients (p < 0.0043), with TIL levels highest in ER-low, followed by Island and Scatter subgroups. Island tumors were enriched in CD36, GZMB, and type I interferon genes; additionally, 23 "ISLAND" genes showed significant prognostic differences in the TCGA BRCA ER-int (10-69%) cohort.

Conclusion: This study emphasizes the importance of recognizing heterogeneity within the ER-int subtype. Identifying distinct ER staining patterns and prognostic significance of TILs and transcriptome in ER-int tumors suggests the need for individualized treatment strategies for Island subtype.

Background: The role of postmastectomy radiotherapy (PMRT) in breast cancer (BC) with nodal micrometastases (N1mic) remains unclear. This study aimed to evaluate the efficacy of PMRT in T1-2N1mic BC patients who have undergone mastectomy.

Methods: Female patients with T1-2N1mic BC who underwent mastectomy and were registered in the Surveillance, Epidemiology, and End Results database between 2010 and 2017. The chi-square test, logistic regression analysis, Kaplan-Meier methods, and multivariate Cox proportional hazards analysis were used for statistical analyses. Nomograms for predicting breast cancer-specific survival (BCSS) and overall survival (OS) were created by integrating the independent prognostic factors.

Results: A total of 5948 eligible patients were included in this study. A total of 1207 patients (20.3%) received PMRT, while 4741 patients (79.7%) did not. The use of PMRT increased over the study period, from 15.7% in 2010 to 23.8% in 2017 (P < 0.001). The multivariate Cox proportional hazards analysis showed that PMRT did not improve BCSS and OS. Nomograms were established based on the independent prognostic factors to predict the BCSS and CSS of patients. Regarding BCSS, there were 3627 patients (61.0%) classified as low-risk and 2321 patients (39.0%) classified as high-risk using a cutoff point of 125, PMRT did not improve BCSS in patients with low-risk (P = 0.697) and high-risk (P = 0.149) groups. Regarding OS, there were 4791 patients (80.5%) classified as low-risk and 1157 patients (19.5%) classified as high-risk using a cutoff point of 130, patients who received PMRT had significantly better 5-year OS than those who did not receive PMRT (P = 0.047), while similar outcomes were found between the treatment arms in the low-risk group (P = 0.575).

Conclusions: While our findings suggest that PMRT does not enhance survival outcomes in T1-T2N1mic BC patients, it may offer a survival advantage in high-risk subgroups.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited targeted therapies and high recurrence rates. While immune checkpoint inhibitors (ICIs) have shown promise, their efficacy as monotherapy is limited. Clinically, ICIs demonstrate significant benefit primarily when combined with chemotherapy, particularly in the neoadjuvant setting for early-stage TNBC, which yields superior outcomes compared to adjuvant therapy. This review elucidates the tumor immunological principles underlying these observations. We discussed how the suppressive tumor microenvironment (TME), progressive T cell exhaustion, and associated epigenetic scarring constrain ICI monotherapy effectiveness. Crucially, we highlight the immunological advantages of the neoadjuvant approach: the presence of the primary tumor provides abundant antigens, and intact tumor-draining lymph nodes (TDLNs) act as critical sites for ICI-mediated priming and expansion of naïve and precursor exhausted T cells. This robust activation within TDLNs enhances systemic anti-tumor immunity and expands the T cell repertoire, a process less effectively achieved in the adjuvant setting after tumor resection. These mechanisms provide a strong rationale for the improved pathological complete response (pCR) rates and event-free survival observed with neoadjuvant chemoimmunotherapy, as demonstrated in trials like KEYNOTE-522. We further explore the implications for adjuvant therapy decisions based on treatment response, the challenges of ICI resistance, the need for predictive biomarkers, management of immune-related adverse events (irAEs), and future therapeutic directions. Understanding the dynamic interplay between chemotherapy, ICIs, T cells, and the TME, particularly the role of TDLNs in the neoadjuvant context, is essential for optimizing immunotherapy strategies and improving outcomes for patients with TNBC.

Purpose: To clarify particularly how febrile neutropenia-related hospitalization (FNH) affects patients' daily lives, by analyzing real-world data on FNH among patients with early breast cancer (EBC) receiving perioperative chemotherapy in Japan.

Methods: This retrospective nationwide large-scale database study was conducted using anonymized claims data from 2010 to 2020. The patients with EBC who had available surgical records were included. Men, those aged < 18 years, and those who had not available chemotherapy records were excluded. FNH was defined as hospitalization during perioperative chemotherapy for EBC, with administration of intravenous antibacterial drugs and a diagnosis of FN, sepsis, infection, or fever.

Results: The analysis population included 33,310 EBC patients with a mean age of 56.9 years, who received a total of 267,535 perioperative chemotherapy cycles. FNH occurred in 1,910 patients (5.73%) and 2144 chemotherapy cycles (0.80%). Median duration of FNH was 6.0 days. Fourth-generation cephalosporins were the most used intravenous antibacterial drugs (50.42%). Median duration of intravenous antibacterial drugs administration was 4.0 days. Therapeutic granulocyte-colony stimulating factor (G-CSF) was used in 1285 patients (67.28%). Median cost for FNH was estimated to be 189 thousand yen in 1,474 chemotherapy cycles with FNH, in which patients received intravenous antibacterial drugs administration for 3-8 days.

Conclusion: This nationwide real-world data analysis revealed the incidence, duration, treatment patterns, and medical cost of FNH in patients with EBC receiving perioperative chemotherapy in Japan. These findings indicate that FNH imposes a considerable burden on patients' daily lives, including time and financial impacts, contributing to the implementation of appropriate shared decision-making for primary G-CSF prophylaxis.

Polymorphous adenocarcinoma-like (PmA-like) tumor of the breast is a rare salivary gland-like neoplasm, with few cases reported globally. We present the first case of a PmA-like tumor with a fibrous pseudocapsule from Japan, including radiological findings. A 40-year-old premenopausal woman presented with a painful mass in the right breast. Mammography revealed a high-density oval mass with predominantly circumscribed margins, while ultrasonography showed a hypoechoic oval mass with heterogeneous internal echoes and vascularity. Both imaging modalities suggested malignancy, prompting a vacuum-assisted biopsy. Histopathological evaluation demonstrated diverse growth patterns and positivity for cytokeratin (CK) 7 and Bcl-2. Initially diagnosed as an unusual ductal proliferation, malignancy could not be excluded, leading to lumpectomy. The resected tumor measured 26 mm, exhibited a fibrous pseudocapsule with focal disruption, and showed varied histological patterns, including solid, cribriform, glandular, and cord-like structures. Immunohistochemistry revealed expression of CK7, S100, vimentin, CK5/6, E-cadherin, Bcl-2, p63, and smooth muscle actin (SMA), with no expression of p40, estrogen receptor, progesterone receptor, HER2, c-Kit, or androgen receptor. These findings, including penetration beyond the capsule, supported the diagnosis of an invasive PmA-like tumor of the breast. Following surgery, the patient underwent additional resection and sentinel lymph node biopsy due to a positive margin. No residual tumor or nodal metastases were found. The patient declined adjuvant therapy and remains recurrence-free after 26 months of follow-up. PmA-like tumors of the breast present diagnostic challenges due to their rarity and diverse histopathological features. Further studies are necessary to characterize their clinical behavior and guide management strategies.

Human epidermal growth factor receptor 2 (HER2) status is crucial for the classification of breast cancer and the selection of its treatment. Although HER2-low breast cancer is a recognized therapeutic subgroup, the classification of HER2 immunohistochemistry (IHC) 0 remains unclear. We reassessed 58 HER2-null breast cancer cases using an enhanced HER2 IHC protocol and the VENTANA OptiView detection system. HER2 expression was evaluated based on membrane positivity rate (%) and staining intensity. Microscopic assessment was performed to determine the percentage of HER2-positive tumor cells. Digital image analysis was used to quantify staining intensity. Detectable membrane HER2 positivity was observed in all tumors previously classified as HER2-null; the positivity rates ranged from 0.33% to 90% and the staining intensity indicated both inter- and intratumoral heterogeneity. These findings suggest that enhanced HER2 IHC protocols can improve detection sensitivity. This approach may help to refine HER2 classification and optimize patient selection for HER2-targeted therapies. Further research is needed to determine the clinical significance of HER2 expression detected using enhanced protocols.

Purpose: Different surgical options existed in the management of axilla among breast cancer patients who were initially node-positive and were converted node-negative after neoadjuvant systemic treatment (NST). De-escalation of axillary surgery was feasible, but previous studies focused on the false-negative rate (FNR) of respective procedures. The aim of this study is to evaluate the oncological outcomes of sentinel lymph-node biopsy (SLNB), MARI procedure, and targeted axillary dissection (TAD).

Patients and methods: PubMed, Embase, and the Cochrane library literature databases were searched systematically. Studies were eligible if they addressed the axillary recurrence rate of patients with nodal pathological complete response (pCR) and omission of axillary lymph-node dissection (ALND) after NST. Pooled analysis was performed using inverse variance methods for logit transformed proportions.

Results: Eleven retrospective studies and three prospective studies involving 4268 patients with node-positive breast cancers were included. A total of 1650 patients achieved nodal pCR and avoided ALND, 1382 patients with SLNB only and 268 patients with MARI/TAD. The pooled estimate of axillary recurrence was 2.1% (95%CI 1.4-3.2%) for patients with negative SLNB and 1.5% (95% CI 0.5-4.1%) for patients with negative MARI/TAD. There was no significant benefit of ALND over SLNB in patients with nodal pCR after NST. Pooled estimates of 5-year DFS, DDFS, and OS of SLNB alone were 0.87 (95% CI 0.83-0.90], 0.90 (95% CI 0.88-0.92), and 0.92 (95% CI 0.88-0.94), respectively.

Conclusion: Breast cancer patients who are converted node-negative after NST have extremely low nodal recurrence rate, irrespective of the choice of axillary surgery. Omission of ALND is oncologically safe in patients who have nodal pCR after NST.