Breast Cancer最新文献

{"title":"Effects of breast size on breast reconstruction in BRCA mutation carriers and genetic high-risk patients after bilateral mastectomy.","authors":"Martin C Lam, Vendela Grufman, Sonia Fertsch, Florian Recker, Nicole E Speck, Jian Farhadi","doi":"10.1007/s12282-025-01691-w","DOIUrl":"10.1007/s12282-025-01691-w","url":null,"abstract":"<p><strong>Background: </strong>Women with genetic susceptibility to breast cancer and indication for bilateral mastectomy are more likely to undergo implant-based breast reconstruction (IBR) than autologous breast reconstruction (ABR), while the impact of breast size in this context is insufficiently studied. Ultimately, comparative data on IBR and different types of ABR beyond abdominal-based flaps in genetic susceptible women remain scarce. This study aimed to evaluate factors associated with ABR and the effects of breast size for bilateral reconstruction in high-risk patients.</p><p><strong>Methods: </strong>A 2.5-year retrospective study was conducted at a single institution including all genetic high-risk patients who underwent bilateral mastectomy and breast reconstruction. Patients were stratified into two groups based on the weight of the mastectomy specimen. Small breast sizes were defined by mastectomy weights below 400 g, and medium-to-large breasts by specimen weights above 400 g. Binary logistic regression was performed to assess variables predictive of ABR, followed by an analysis of the breast size-dependent reconstructive algorithm and its complication rates.</p><p><strong>Results: </strong>We included 71 patients with BRCA1/2 (97.2%), CHEK2 (1.4%), and PALB2 (1.4%) mutations in the study. Among those, 68 IBRs and 74 ABRs were performed. Increasing age, immediate reconstruction, and medium-to-large breast size were predictive of ABR compared to IBR (p < 0.05). In the IBR-group, the majority of preoperative small breasts received subpectoral implant placements (81.0%, p = 0.003), while prepectoral implants (53.9%, p = 0.003) were preferred in medium-to-large breasts. In the ABR-group, the deep inferior epigastric artery (DIEP) flap was the choice in the vast majority of cases with larger breasts (86.4%, p < 0.001), whereas the transverse myocutaneous gracilis (TMG) flap (46.7%, p < 0.001) and superior gluteal artery perforator (SGAP) flap (20.0%, p = 0.002) were only considered in small-breasted patients. No elevated incidence of overall complications with increasing breast size was found. However, patients with larger breasts were more likely to undergo elective revisions after IBR (p < 0.001) as well as ABR (p = 0.013). With regard to two-stage tissue expander reconstructions, high-risk patients with larger breast size revealed increased explantations (p = 0.043) and expander-related revisions requiring additional surgery (p = 0.003). The latter was significantly reduced by reduction mammoplasty prior to expander placement (p = 0.036).</p><p><strong>Conclusions: </strong>The preoperative breast size of gene mutation carriers influences the postmastectomy reconstructive choice. TMG and SGAP flaps are suitable options for bilateral reconstruction of genetic susceptible patients with small breasts, while DIEP flaps are preferred in larger breast sizes. With increasing breast size an elevated risk for elective revisions after either","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"582-595"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c-Myc knockdown restores tamoxifen sensitivity in triple-negative breast cancer by reactivating the expression of ERα: the central role of miR-152 and miR-148a.","authors":"Chao Dong, Yonghong Sun, Xiaoli Xu, Huiling Li, Xinyu Song, Wenxin Wei, Chong Jiao, Haoyi Xu, Yuanjing Liu, Zuliyaer Mierzhakenmu, Li Li, Binlin Ma","doi":"10.1007/s12282-025-01683-w","DOIUrl":"10.1007/s12282-025-01683-w","url":null,"abstract":"<p><strong>Background: </strong>Poor prognosis of triple-negative breast cancer (TNBC) is owing to its intrinsic heterogeneity and lack of targeted therapies. Emerging evidence has characterized that targeting c-Myc might be a promising way to treat TNBC.</p><p><strong>Methods: </strong>c-Myc knocked down TNBC cells were generated and the tamoxifen sensitivity was determined. Methylation-specific PCR analysis was used to detect the methylation status of ERα promoter, and c-Myc-mediated miRNA transcription was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. The in vivo tamoxifen sensitivity was determined by mouse xenograft model.</p><p><strong>Results: </strong>c-Myc knockdown in TNBC cells leads to the reactivation of ERα and consequent acquisition its sensitivity to tamoxifen. c-Myc depletion decreased the methylation in the promoter of ERα and DNMT1 was identified as the main executor. c-Myc knockdown-induced tamoxifen sensitivity was reversed by DNMT1 overexpression. The expression of miR-152-3p and miR-148a-3p was largely induced in c-Myc knockdown TNBC cells, and both miR-152-3p and miR-148a-3p could target DNMT1 to regulate its expression. c-Myc binds to the promoter regions of miR-152-3p and miR-148a-3p to exert transcriptional suppression. By suppressing miR-152-3p or miR-148a-3p expression using inhibitors, enhanced sensitivity to tamoxifen induced by c-Myc knockdown was partially reversed. In vivo xenograft tumor model demonstrated that c-Myc knockdown mildly inhibits the growth of tumor, and a dramatic decline was observed when administrated with tamoxifen combined with c-Myc knockdown.</p><p><strong>Conclusion: </strong>Our study first illustrated that c-Myc knockdown in TNBC cells reactivate ERα expression in a miR-152/miR-148a-DNMT1-dependent manner, and brought new sights into treating TNBC using hormonal therapies.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"529-542"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SET-binding protein 1 (SETBP1) suppresses cell proliferation in estrogen receptor-positive breast cancer.","authors":"Yuki Ando, Takaaki Masuda, Naoki Hayashi, Keisuke Kosai, Shohei Shibuta, Yuya Ono, Tobo Taro, Hajime Otsu, Yuichi Hisamatsu, Tomoharu Yoshizumi, Koshi Mimori","doi":"10.1007/s12282-025-01667-w","DOIUrl":"10.1007/s12282-025-01667-w","url":null,"abstract":"<p><strong>Background: </strong>The single-nucleotide polymorphism rs6507583 at the promoter of SET-binding protein 1 (SETBP1) was implicated in estrogen receptor (ER)-positive breast carcinogenesis. Here, we evaluated the clinical and biological relevance of SETBP1 expression in ER-positive breast cancer (BC).</p><p><strong>Methods: </strong>The associations between SETBP1 expression and clinical outcomes in BC patients were analyzed in independent cohorts. The localizations of SETBP1 expression in BC tissues were observed by immunohistochemical staining. Pathway analyses were conducted using TCGA dataset. In vitro proliferation assay, protein phosphatase 2A (PP2A) activity assay, and gene expression analysis were performed in SETBP1-knockdown ER-positive BC cells. We investigated the factors influencing SETBP1 mRNA expression using TCGA dataset. rs6507583 presence and SETBP1 mRNA expression in 11 mammary cell lines and 56 BC tissue samples were examined by target sequencing and RT-qPCR, respectively.</p><p><strong>Results: </strong>SETBP1 was downregulated in BC cells compared with normal ductal epithelial cells. Low SETBP1 mRNA expression was an independent prognostic factor for poor recurrence-free survival. Pathway analyses revealed an inverse relationship between decreased SETBP1 expression and the expression of E2F, MYC, and G2M checkpoint target genes in BC tissues. SETBP1 knockdown promoted proliferation, inhibition of PP2A activity, and phosphorylation of MAPK in ER-positive BC. Low SETBP1 expression was influenced by high SETBP1 promoter methylation and DNA copy number SETBP1 deletion. SETBP1 expression with rs6507583 was lower than without rs6507583 in BC.</p><p><strong>Conclusions: </strong>We demonstrated that low SETBP1 expression could be a poor prognostic biomarker that promotes ER-positive BC proliferation, possibly via phosphorylation of MAPK.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"457-469"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and internal validation of a predictive model of overall and progression-free survival in eribulin-treated patients with breast cancer based on baseline peripheral blood parameters.","authors":"Keiko Natori, Masataka Igeta, Takashi Morimoto, Masayuki Nagahashi, Sadako Akashi-Tanaka, Takashi Daimon, Yasuo Miyoshi","doi":"10.1007/s12282-025-01678-7","DOIUrl":"10.1007/s12282-025-01678-7","url":null,"abstract":"<p><strong>Background: </strong>Immune and inflammatory blood parameters have been reported as biomarkers for treatment efficacy. This study aimed to establish a predictive model that includes blood parameters for patients with metastatic breast cancer treated with eribulin.</p><p><strong>Methods: </strong>A total of 297 patients were enrolled, and their baseline neutrophil-to-lymphocyte ratio, absolute lymphocyte count (ALC), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH), C-reactive protein (CRP), and clinical data were retrospectively collected.</p><p><strong>Results: </strong>We constructed nomograms to predict overall survival (OS) and progression-free survival (PFS) using blood parameters, including clinical factors. For OS, menopausal status, hormone receptor status, HER2 status, de novo or recurrent, metastatic site, treatment line, ALC, PLR, PNI, LMR, LDH, and CRP were selected to predict the model. We used menopausal status, hormone receptor status, HER2 status, treatment line, PLR, LMR, LDH, and CRP to predict PFS. Both the OS and PFS of patients according to the risk scores were significantly different (p < 0.001). The optimism-corrected C-indices of the nomograms for OS and PFS were 0.680 and 0.622, respectively. The mean time-dependent area under the receiver operating curve values for OS at 1, 2, and 3 years were 0.752, 0.761, and 0.784, respectively, and for PFS at 3, 6, and 12 months were 0.660, 0.661, and 0.650, respectively.</p><p><strong>Conclusion: </strong>Nomograms incorporating peripheral blood parameters may improve the accuracy of predicting OS and PFS in patients treated with eribulin. Our prediction model may help decision-making for breast cancer patients who are considering eribulin treatment.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"500-511"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Clinicopathological significance of androgen receptor expression and tumor infiltrating lymphocytes in triple-negative breast cancer: a retrospective cohort study.","authors":"Takeshi Ushigusa, Nami Hirakawa, Yuka Kajiura, Atsushi Yoshida, Hideko Yamauchi, Naoki Kanomata","doi":"10.1007/s12282-025-01688-5","DOIUrl":"10.1007/s12282-025-01688-5","url":null,"abstract":"","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"616-618"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective cohort study of abemaciclib-induced interstitial lung disease in metastatic breast cancer after chemotherapy.","authors":"Sayuka Nakayama, Takayuki Iwamoto, Kazuhiro Araki, Kazutaka Narui, Takahiro Nakayama, Hiroyuki Nagase, Naoya Sugimoto, Naruto Taira, Tomohiko Aihara, Yuichiro Kikawa, Hirofumi Mukai","doi":"10.1007/s12282-025-01680-z","DOIUrl":"10.1007/s12282-025-01680-z","url":null,"abstract":"<p><strong>Background: </strong>The safety of combination therapy with abemaciclib and hormone therapy in patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) who were previously treated with chemotherapy for MBC remains unclear. Caution is required as the Pharmaceuticals and Medical Devices Agency (PMDA) and the U.S. Food and Drug Administration (FDA) have issued warnings about abemaciclib-induced interstitial lung disease (ILD).</p><p><strong>Methods: </strong>This study was a secondary analysis of a prospective observational study involving patients who had previously undergone chemotherapy for HR + MBC. A certificated respiratory specialist reviewed the clinical information of patients who were suspected of having ILD to adjudicate abemaciclib-induced ILD and definitively diagnosed abemaciclib-induced ILD. In this study, the incidence, risk factors, and clinical course of interstitial lung disease (ILD) are reported.</p><p><strong>Results: </strong>All cases of patients who received abemaciclib had no radiological evidence of ILD prior to abemaciclib treatment. The incidence of abemaciclib-induced ILD was 7.4% (n = 9/122). CTCAE grade 1/2 occurred in 77.8% (n = 7), with no grade 4/5 cases. The timing of ILD onset varied and our study did not identify any significant risk factors for abemaciclib-induced ILD. All cases of ILD ultimately were confirmed to be in remission or cured.</p><p><strong>Conclusion: </strong>In this multicenter prospective cohort study with a follow-up period of 3.3 years and a definition of ILD by a certified pulmonologist, we accurately evaluated abemaciclib-associated ILD after chemotherapy. The favorable clinical course of ILD indicate that abemaciclib treatment is an acceptable option for these MBC patients. However, because abemaciclib-induced ILD is difficult to predict, careful monitoring is required during abemaciclib treatment.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"607-612"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific types of anxiety regarding radiation therapy in patients with breast cancer: a longitudinal study.","authors":"Shi-Jia Wang, Xin Feng, Wei Zhang, Hui Fang, Hao Jing, Yu Tang, Tao Li, Shu-Nan Qi, Yong-Wen Song, Wen-Wen Zhang, Ning-Ning Lu, Yuan Tang, Yue-Ping Liu, Bo Chen, Xin Liu, Ye-Xiong Li, Yi-Rui Zhai, Shu-Lian Wang","doi":"10.1007/s12282-025-01690-x","DOIUrl":"10.1007/s12282-025-01690-x","url":null,"abstract":"<p><strong>Purpose: </strong>The radiotherapy categorical anxiety scale (RCAS) was designed to evaluate the specific types of radiation therapy (RT)-related anxiety in cancer patients. We translated RCAS into Chinese, evaluated its reliability and validity in breast cancer (BC) patients, and used it to evaluate changes in specific types and levels of RT-related anxiety throughout RT.</p><p><strong>Methods: </strong>This was a prospective, longitudinal study enrolling 504 Chinese BC patients receiving RT. The patients completed questionnaires assessing the specific types of RT-related anxiety (our Chinese version of RCAS), depression [Patient Health Questionnaire-9 (PHQ-9)], and anxiety [Generalized Anxiety Disorder-7 (GAD-7)] before, during, and after RT. Emotional distress (ED) was defined as a PHQ-9 or GAD-7 score of > 4. Generalized estimating equation was performed to evaluate changes in total and subscale scores on RCAS. Multivariable general linear models were used to explore independent predictors of baseline RCAS scores.</p><p><strong>Results: </strong>Our Chinese version of RCAS demonstrated high internal consistency (Cronbach's α = 0.89-0.92). Our data demonstrated a Kaiser-Meyer-Olkin measure of 0.946 and P < 0.001 on the Bartlett sphericity test, indicating their suitability for subsequent confirmatory factor analysis (CFA). CFA further demonstrated its adequate convergent and discriminant validity. The levels of anxiety related to RT environment decreased over time, whereas those of anxiety related to RT treatment efficacy remained stable throughout the treatment. Patients demonstrated higher scores on items regarding side effects and treatment efficacy of RT than on other items. ED before RT independently predicted for higher baseline RCAS score.</p><p><strong>Conclusions: </strong>Our Chinese version of the RCAS can be used to quantitatively evaluate specific types of RT-related anxiety in Chinese BC patients. Clinicians should pay more attention to anxiety regarding the side effects and treatment efficacy of RT reported by their patients, particularly those with baseline ED.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"596-606"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated sentinel lymph node biopsy for local recurrence after breast-conserving surgery.","authors":"Yuka Matsubara, Nobuyasu Suganuma, Shogo Nakamoto, Yuichiro Kikawa, Takayuki Iwamoto, Takashi Yamanaka, Tatsuya Yoshida, Toshinari Yamashita, Aya Saitou","doi":"10.1007/s12282-025-01679-6","DOIUrl":"10.1007/s12282-025-01679-6","url":null,"abstract":"<p><strong>Background: </strong>In the realm of surgical therapy for cN0 early breast cancer, sentinel lymph node biopsy (SNB) has been established as a technique that allows the omission of axillary lymph node dissection (Ax) while maintaining local control in the axillary region.</p><p><strong>Methods: </strong>This retrospective study analyzed data from 52 patients who underwent reSNB for IBTR after initial breast-conserving surgery at Kanagawa Cancer Center between June 2012 and March 2019. reSNB was conducted using both the dye and radioactive isotope methods. The identification rate was defined as the number of cases in which sentinel lymph nodes were visualized on lymphoscintigraphy images divided by the total number of cases. The identification rate was compared according to the initial surgical procedure.</p><p><strong>Results: </strong>Overall, the identification rate for reSNB was 94.2%. The identification rate for reSNB in the axilla was higher in patients who initially underwent SNB than in those who initially underwent axillary lymph node dissection (83.3% vs. 42.9%). ReSNB positivity was observed in three patients (6.7%) in the ipsilateral axilla, whereas no metastasis was detected in the contralateral axilla or internal mammary region. Although four cases of recurrence were observed after reoperation, there was no local recurrence in the ipsilateral axillary region.</p><p><strong>Conclusions: </strong>reSNB demonstrated high identification rates, comparable to those of initial SNB, with a low rate of positive metastasis and no local recurrence in the ipsilateral axillary region. Despite the limited number of cases, these findings suggest the clinical significance of reSNB in IBTR cases.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"512-519"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining the role of surgery in de novo stage IV breast cancer: the need for biomarkers and mechanistic insights.","authors":"Mariam Rizk, Kefah Mokbel","doi":"10.1007/s12282-025-01681-y","DOIUrl":"10.1007/s12282-025-01681-y","url":null,"abstract":"","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"613-614"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-derived stem cells enhance the tumorigenic potential of pre-malignant breast epithelial cells through paracrine activation of PI3K-AKT pathway.","authors":"Qifeng Wu, Jinguang He, Tanja Herrler, Baofu Yu, Qimin Zhou, Danning Zheng, Xiaoxue Chen, Yangxuanyu Yan, Chuanchang Dai, Kai Liu, Gangming Zou, Shengfang Ge, Yunbo Qiao, Qingfeng Li, Jiao Wei","doi":"10.1007/s12282-025-01686-7","DOIUrl":"10.1007/s12282-025-01686-7","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs)-assisted fat grafting has emerged as a widely used procedure for breast reconstruction post mastectomy and for aesthetic augmentation. Given the limited cases of breast cancer following grafting, the oncological safety of this procedure remains controversial.</p><p><strong>Methods: </strong>The effects of ADSCs on the oncogenic features of premalignant MCF-10AT cells were investigated using co-culture and xenograft models. We further evaluated the malignancy-promoting effect of ADSCs in a 7,12-Dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. RNA-sequencing was performed on ADSCs, MCF-10AT cells, and ADSC-co-cultured MCF-10AT cells. Protein changes in ADSC/MCF-10AT co-culture medium and MCF-10AT cells were determined by proteomic analysis. Pathway inhibitors were used to investigate signaling pathways involved in the ADSC-induced oncogenic changes of MCF-10AT cells.</p><p><strong>Results: </strong>We found that ADSCs promoted the proliferation and migration of MCF-10AT cells, and co-injection of ADSCs increased the tumor incidence of MCF-10AT cells from 29% to 58% in nude mice. Additionally, grafted ADSCs significantly enhanced tumor incidence, growth, and distant metastasis in the DMBA-induced rats, while it could not induce tumorigenesis in normal breast tissues. Combined RNA-sequencing and proteomic analysis demonstrated that the paracrine factors secreted by ADSCs robustly activated the oncogenic PI3K-AKT signaling in MCF-10AT cells. We also revealed the auto-activated TGF-beta and Wnt pathways in co-cultured MCF-10AT cells, which may be synergistic in tumor formation and progression. As expected, blocking these pathways, especially the PI3K-AKT pathway, strongly diminished the promoting effects of ADSCs, suggesting their potential as therapeutic targets for ADSC grafting-associated breast tumors.</p><p><strong>Conclusions: </strong>Our data illustrated the synergistic effect between ADSC paracrine factors and MCF-10AT auto-activated pathways in the carcinogenesis of MCF-10AT cells through activation of the oncogenic PI3K-AKT pathway. Based on these findings, we strongly recommend pre-operative examinations for breast cancer risk factors before ADSC-associated transplantation.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"552-565"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}