Breast Cancer Research and Treatment最新文献

Purpose: To study the association between clinicopathologic characteristics of ductal carcinoma in situ (DCIS) and risk of subsequent invasive breast cancer (IBC).

Methods: We conducted a case-control study nested in a multicenter, population-based cohort of 8175 women aged ≥ 18 years with DCIS diagnosed between 1987 and 2016 and followed for a median duration of 83 months. Cases (n = 497) were women with a first diagnosis of DCIS who developed a subsequent IBC ≥ 6 months later; controls (2/case; n = 959) were matched to cases on age at and calendar year of DCIS diagnosis. Univariable and multivariable conditional logistic regression models were used to examine the associations between the DCIS characteristics of interest (non-screen detection of DCIS, tumor size, positive margins, grade of DCIS, necrosis, architectural pattern, microcalcification, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status) and risk of IBC.

Results: In the total study population, the associations were largely null. In subgroup analyses, there were strong position associations with punctate necrosis (pre/perimenopausal women), detection by physical exam (postmenopausal women), architectural patterns other than the main types (breast-conserving surgery [BCS]), and DCIS margins (ipsilateral cases), and inverse associations with HER2 positivity (BCS) and microcalcification (mastectomy); however, the associated confidence intervals were mostly very wide.

Conclusion: The results of this study provide limited support for associations of the DCIS clinicopathologic characteristics studied here and risk of IBC.

Purpose: Precise tumor excision is important in breast-conserving surgery (BCS). This study explores the safety and accuracy of fluorescence image-guided BCS (FIGS) using a lidocaine mucilage-ICG compound (L-ICG).

Methods: 54 patients who underwent BCS from August 2020 to September 2023 were enrolled. L-ICG was locally injected 0.5 cm from the tumor border. FIGS was performed to guide the tumor excision. Frozen sectioning of surgical field biopsies was used to assess the intraoperative margin status. The primary outcome measures were margin width and positive margin rates. Cosmetic outcome was evaluated by the modified version of Breast-QTM Breast-Conserving Therapy Module (Postoperative) and breast cosmetic outcome assessment criteria.

Results: The median cranial, caudal, medial, and lateral margin widths were 8 mm (interquartile range [IQR], 3-14), 5.5 mm (IQR, 2-15), 6 mm (IQR, 3-15), and 8 mm (IQR, 3-15), respectively. Five out of 54 (9.3%) patients had an intraoperative positive margin. Intraoperatively extended resection was performed for four patients and mastectomy for the remaining one. This further reduced the positive margin rate to 1.9% at final histopathology. 50 patients received cosmetic outcome evaluation, 100% of them were "somewhat satisfied" or "very satisfied" with the appearance of the operated breast when clothed and 98% of them were scaled as "Good" or "Excellent" in their appearance of the operated breast. No serious adverse events were observed. With a median follow-up of 12.8 months, no events for tumor relapse were observed.

Conclusion: L-ICG-based FIGS is a promising technique to guide precise tumor excision in BCS.

Background: Cryotherapy with taxane infusion is a noninvasive strategy for preventing peripheral neuropathy (PN), but the efficacy of this approach has not been proven.

Methods: A systematic search was conducted, and 477 records were initially identified. The titles were screened independently by 2 reviewers. Fourteen studies were ultimately included for meta-analysis, which was conducted using the meta package in the R software. Only studies that analysed cryotherapy use in breast cancer patients who received paclitaxel or nab-paclitaxel were included. Relative risks (RRs) were calculated using the random effects model to compare the occurrence of PN between the paclitaxel and nab-paclitaxel groups.

Results: The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 PN was 24.85% (81/326) in the cryotherapy arm and 42.35% (72/170) in the placebo arm. The overall RR CTCAE grade ≥ 2 PN in the cryotherapy group compared with the placebo group was 0.45 [0.27, 0.77, p = 0.0031]. The RR for sensory PN was 0.19 [0.05, 0.66, p = 0.009], and that for motor PN was 0.18 [0.03, 0.99, p = 0.0491]. The RR for Patient Neurotoxicity Questionnaire (PNQ) scores ≥ D, which indicate severe neuropathy, was 0.24 [0.09, 0.62; p = 0.0035]. Cold intolerance was the most reported t adverse effect, with a prevalence of 15% (37/247).

Conclusions: The use of cryotherapy decreased the occurrence of CTCAE grade ≥ 2 PN by 55%. Cold intolerance was the most frequently reported adverse effect associated with cryotherapy, but this adverse effect did not lead to high discontinuation rates.

Purpose: The purpose of this study was to evaluate the feasibility and safety of indocyanine green (ICG) fluorescence as an alternative to traditional sentinel lymph node biopsy (SLNB) techniques in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). Specifically, the study aimed to assess sentinel node identification rates and the effectiveness of ICG in axillary staging without the use of radioactive tracers.

Methods: This retrospective study included 71 BC patients treated with NAC, who underwent SLNB using ICG fluorescence between 2020 and 2024. ICG was injected intradermally around the nipple-areolar complex, and the lymphatic pathways were visualized with a fluorescence camera. SN identification rate (IR) and retrieval of three or more SNs were the primary and secondary endpoints, respectively. Statistical analyses were performed using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables.

Results: ICG-guided SNs were identified in 91.5% of patients, with a median retrieval time of 25 min (range: 10-50). Three or more SNs were successfully collected among 66.2% of cases and 38% of patients achieved a complete pathological response to NAC, while 53.5% had partial responses. Metastatic SNs were found in 21.1% of patients, and no serious intraoperative or postoperative complications were observed.

Conclusion: ICG fluorescence-guided SLNB proved to be a feasible and promising method for SNs identification among BC patients after NAC. While ICG shows potential as an alternative to traditional techniques, further studies are required to confirm these findings and to establish ICG role in post-NAC axillary staging.

Purpose: To evaluate the prognostic significance of changes in pre- and post-neoadjuvant chemotherapy (NACT) Ki67 in patients with primary invasive triple-negative breast cancer (TNBC).

Methods: Population-based registry data were retrieved for patients diagnosed with TNBC between 2007 and 2021 (n = 9262). Multivariable Cox regression analysis was performed for disease-specific survival (DSS) and overall survival (OS) adjusted for age and residual disease in the breast and nodes (RDBN).

Results: Of the 1777 TNBC patients receiving NACT, 54 achieved pathologic complete response (pCR) and 755 had residual disease. Most patients were overweight with stage II disease (78%), grade 3 tumors (53%), and RDBN score 3 (42%). Compared to baseline, tumor size (30 vs. 15 mm; P < 0.0001) and Ki67 levels (63% vs. 48%; P < 2.2e - 16) generally decreased after NACT. Although only 5% of samples increased in size, Ki67 levels often remained unchanged (75%) or increased (0.9%) after treatment, respectively. However, 34% of patients discontinued treatment. Patients showing no changes in Ki67% had more unfavorable OS (P < 0.0001) and DSS (P = 0.00032), with significantly lower 5-year survival probabilities (OS: 66%; DSS: 78%) than those with decreased Ki67% (OS: 87%; DSS: 89%). All patients reaching pCR were alive 5 years after diagnosis. However, only the RDBN score was an independent predictor of survival in the multivariable analyses.

Conclusion: Ki67 often remained unchanged in TNBC patients treated with neoadjuvant chemotherapy, resulting in adverse clinical outcomes. These findings highlight the need for individualized treatment regimens and dynamic monitoring of TNBC patients with high Ki67 post-NACT.

Purpose: Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process. In addition, secretion of bone morphogenetic protein 1 (BMP-1), which is crucial for the proteolytic release of TGF-β, was markedly high in metastatic mammary cancer cells compared to non-metastatic cells. Although TGF-β inhibitors are in clinical trials, systemic inhibition of TGF-β may produce heavy side effects. We here hypothesize that inhibition of BMP-1 proteolytic activity inhibits TGF-β activity and induces anti-tumoral effects.

Method and results: Effects of specific BMP-1 inhibitor on liver and brain metastatic murine mammary cancer cells (4TLM and 4TBM), as well as on human mammary cancer MDA-MB-231 and MCF-7 cells, were examined and compared with the results of TGF-β inhibition. Inhibition of BMP-1 activity markedly suppressed proliferation of cancer cells and enhanced anti-tumoral effects of doxorubicin. Inhibition of BMP-1 activity but not of TGF-β activity decreased colony and spheroid formation. Differential effects of BMP-1 and TGF-β inhibitors on TGF-β secretion was also observed.

Conclusions: These results demonstrated for the first time that the inhibition of BMP-1 activity has therapeutic potential for treatment of metastatic mammary cancer and enhances the anti-tumoral effects of doxorubicin.

Purpose: The incidence of breast cancer has been increasing in recent years, and monotherapy approaches are not sufficient alone in the treatment of breast cancer. In the combined therapy approach, combining two or three different agents in lower doses can mitigate the side effects on living cells and tissues caused by high doses of chemical agents used alone. ABT-263 (navitoclax), a clinically tested Bcl-2 family protein inhibitor, has shown limited success in clinical trials due to the development of resistance to monotherapy in breast cancer cells. This resistance shows that monotherapy approaches are inadequate and more effective treatment strategies are needed. It is the ability of HSP90 inhibitors to destabilize many oncoproteins that are critical for the survival of cancer cells. This study aimed to examine the anticancer activity of the combination of ABT-263 with BIIB021, a new generation HSP90 inhibitor, on two widely used breast cancer cell lines: MCF-7 (ER-positive) and MDA-MB-231 (triple-negative breast cancer, TNBC). These cell lines were selected to represent distinct breast cancer subtypes with different molecular characteristics and clinical behaviors.

Methods: Single and combined cytotoxic effects of this agents on MCF-7 and MDA-MB-231 breast cancer cell lines were determined using the MTT cell viability test. The combined use of these two agents showed a synergistic effect, and this effect was assigned using the Chou and Talalay method. mRNA and protein levels of apoptosis-related genes Bax, Bcl-2, Casp9, and Heat Shock Proteins HSP27, HSP70, and HSP90 were analyzed using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively.

Results: The cytotoxicity analysis, combined with the application of the Chou-Talalay method, demonstrated that the BIIB021 and ABT-263 combination exhibited significantly greater anticancer activity compared to the individual effects of either BIIB021 or ABT-263 in breast cancer cell lines. The analysis of mRNA and protein levels indicated that the BIIB021+ABT-263 combination may have triggered the intrinsic apoptotic pathway in breast cancer cells.

Conclusion: This study showed that co-administration of ABT-263 and BIIB021 agents exhibited synergistic cytotoxic effects and increased the expression of apoptosis-related genes in breast cancer cell lines.

Purpose: Traditional computer-assisted detection (CADe) algorithms were developed for 2D mammography, while modern artificial intelligence (AI) algorithms can be applied to 2D mammography and/or digital breast tomosynthesis (DBT). The objective is to compare the performance of a traditional machine learning CADe algorithm for synthetic 2D mammography to a deep learning-based AI algorithm for DBT on the same mammograms.

Methods: Mammographic examinations from 764 patients (mean age 58 years ± 11) with 106 biopsy-proven cancers and 658 cancer-negative cases were analyzed by a CADe algorithm (ImageChecker v10.0, Hologic, Inc.) and an AI algorithm (Genius AI Detection v2.0, Hologic, Inc.). Synthetic 2D images were used for CADe analysis, and DBT images were used for AI analysis. For each algorithm, an overall case score was defined as the highest score of all lesion marks, which was used to determine the area under the receiver operating characteristic curve (AUC).

Results: The overall AUC was higher for 3D AI than 2D CADe (0.873 versus 0.693, P < 0.001). Lesion-specific sensitivity of 3D AI was higher than 2D CADe (94.3 versus 72.6%, P = 0.002). Specificity of 3D AI was higher than 2D CADe (54.3 versus 16.7%, P < 0.001), and the rate of false marks on non-cancer cases was lower for 3D AI than 2D CADe (0.91 versus 3.24 per exam, P < 0.001).

Conclusion: A deep learning-based AI algorithm applied to DBT images significantly outperformed a traditional machine learning CADe algorithm applied to synthetic 2D mammographic images, with regard to AUC, sensitivity, and specificity.

Purpose: The characteristics of patients with bilateral and unilateral breast cancer at the time of diagnosis or during follow-up have been compared, focusing on the differences in disease-free survival and overall survival between these groups.

Methods: A total of 1,947 patients diagnosed with invasive carcinoma were included in the study. 1876 ​​(96.4%) of our patients had unilateral and 71 (3.6%) had bilateral breast cancer. Among the bilateral breast cancer patients n = 47 were metachronous, while n = 24 were synchronous.

Results: SBBC, which had the lowest OS duration, showed a statistically significant difference compared to MBCC, similar to that observed in unilateral breast cancer (p = 0.027).

Conclusion: The fact that SBBC has the lowest survival rate despite more aggressive treatments should be considered a poor prognostic factor for survival on its own.

Purpose: Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models.

Methods: In vitro, PDT was combined with RT (2.5 Gy) using a porphyrin (TMPyP, 32 μmolL^-1) and red light (660 ± 15 nm) with a dose of 50 Jcm^-2. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels.

Results: Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response.

Conclusion: Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.