Breast cancer (Tokyo, Japan)最新文献

{"title":"Beyond the triad: biological subtypes and the \"safety net\" in omitting sentinel lymph node biopsy.","authors":"Bin Ye, Bo Ma","doi":"10.1007/s12282-026-01848-1","DOIUrl":"10.1007/s12282-026-01848-1","url":null,"abstract":"","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"798-799"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of a multigene assay (MammaPrint/Blueprint) to predict early recurrence of hormone receptor-positive, HER2-negative breast cancer: a case‒control study (WJOG16722B).","authors":"Rurina Watanuki, Hitomi Sakai, Yuri Kimura, Atsushi Yoshida, Yukinori Ozaki, Akemi Kataoka, Natsue Uehiro, Atsushi Fushimi, Hidenori Kamio, Takashi Ikeno, Masashi Wakabayashi, Mayumi Iida, Tsutomu Kawaguchi, Junji Tsurutani, Toshimi Takano","doi":"10.1007/s12282-026-01847-2","DOIUrl":"10.1007/s12282-026-01847-2","url":null,"abstract":"<p><strong>Background: </strong>Hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer generally has a favorable prognosis; however, early postoperative recurrence markedly reduces survival. Accurate prediction of early recurrence is crucial for personalizing treatment. This case-control study compared MammaPrint (MP) and BluePrint (BP) results between early recurrence patients and matched controls.</p><p><strong>Methods: </strong>Patients were selected from our previous study, the WJOG15721B cohort (n = 2732). Those with recurrence within three years after surgery were randomly extracted, and controls matched for institution, clinical stage, and number of pathological lymph node metastases were included (n = 124). Tumor samples underwent MP and BP assays to classify recurrence risk and molecular subtypes.</p><p><strong>Results: </strong>Of 115 submitted tumor samples, 85 were analyzed successfully (43 early recurrence, 42 no recurrence). High-risk MP classification was significantly more frequent in early recurrence patients (79.1% vs. 40.5%, p < 0.001), and Luminal B BP subtype was more common in early recurrence patients (79.1% vs. 38.1%, p < 0.001). High MP risk was associated with high Ki-67 levels and higher nuclear grade. Integrating clinical and genomic risk enhanced prognostic precision: patients with both clinical and genomic high risk had the highest recurrence rate (100%), those with low clinical and genomic risk had the lowest (28.1%), and patients with low clinical but high genomic risk showed an intermediate recurrence rate (57.5%).</p><p><strong>Conclusions: </strong>Compared with patients without recurrence, those with early recurrence showed a significantly higher prevalence of high-risk MP results and Luminal B BP subtype. High-risk MP/Luminal B BP subtype suggested an association with early recurrence in patients with HR + /HER2- early breast cancer.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"693-704"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147523810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-progesterone receptor expression predicts nodal pathological complete response after neoadjuvant chemotherapy in premenopausal patients with ER-positive/HER2-negative breast cancer.","authors":"Naoko Iwamoto, Shin-Ichiro Horiguchi, Takashi Kuwayama, Masakazu Toi","doi":"10.1007/s12282-026-01851-6","DOIUrl":"10.1007/s12282-026-01851-6","url":null,"abstract":"<p><p>BACKGROUND: Estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) shows heterogeneous response to neoadjuvant chemotherapy (NAC). Although low progesterone receptor (PgR) has been associated with greater chemosensitivity, it is unclear whether its predictive value differs according to menopausal status. METHODS: We retrospectively analyzed 213 patients with node-positive, ER-positive/HER2-negative BC who underwent surgery and axillary lymph node dissection (ALND) after NAC between January 2010 and April 2025. All patients received anthracycline- and taxane-based regimens. Multivariable logistic regression was performed to identify predictors of achieving pathological complete response in the axillary lymph node (ypN0), and interaction terms were included to evaluate whether the effect of PgR differed according to menopausal status. RESULTS: Among 213 patients, 47 (22%) achieved ypN0. Clinical complete response (OR 5.29; 95% CI 1.44–19.40; p = 0.01) and high Ki-67 (≥ 30%) (OR 3.62; 95% CI 1.14–11.50; p = 0.03) independently predicted ypN0. Low PgR expression (≤ 5%) and premenopausal status were not independently associated with ypN0. In the final multivariable interaction model, the interaction between low PgR (≤ 5%) and premenopausal status remained significant (OR 9.52; 95% CI 1.22–74.50; p = 0.03). CONCLUSIONS: The association between low PgR status (≤ 5% vs. > 5%) and ypN0 after NAC may differ according to menopausal status and appeared to be more pronounced in premenopausal patients with ER-positive/HER2-negative BC. PgR assessment may help identify patients more likely to achieve ypN0 and may provide additional information for future studies evaluating axillary de-escalation. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"744-751"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent diffusion MRI for non-invasive differentiation of benign and malignant breast lesions and evaluation of proliferation index biomarkers.","authors":"Luqing Ru, Yanlin Tang, Jigeng Zhang, Ran Shi, Dawei Yin, Yong Zhang, Yuan Kong, Jun Du, Peng Wang","doi":"10.1007/s12282-026-01842-7","DOIUrl":"10.1007/s12282-026-01842-7","url":null,"abstract":"<p><p>PURPOSE: To establish a dual-task assessment framework using time-dependent diffusion MRI (td-dMRI) for: (1) differentiating benign from malignant breast lesions classified as BI-RADS category 4, and (2) preoperatively predicting the proliferation marker Ki-67 in invasive ductal carcinoma (IDC). METHODS: This prospective study enrolled 152 consecutive patients between June 2024 and June 2025. Patients with BI-RADS 4 lesions detected on ultrasound/mammography, no prior biopsy or treatment, and scheduled for surgical resection. Modalities included MRI using the IMPULSED protocol with PGSE and OGSE sequences. A two-compartment biophysical model quantified microstructural parameters including intracellular volume fraction (fin), mean cell diameter (d-mean), cellularity, extracellular diffusion coefficient (Dex), and ADC values. The final cohort comprised 42 benign and 102 malignant lesions (82 IDC cases). Multivariable logistic regression identified independent predictors, with diagnostic performance assessed through ROC analysis. RESULTS: A total of 144 patients (mean age, 52.2 ± 9.5 years) were evaluated. All td-dMRI parameters demonstrated significant differences between benign and malignant lesions (p < 0.05). Malignant lesions exhibited significantly lower ADC (PGSE), ADC (OGSE), d-mean, and Dex, but higher cellularity and fin compared with benign lesions. The combined diagnostic model (cellularity + d-mean + ADC (OGSE33Hz)) achieved the highest performance with an AUC of 0.892 (95% CI 0.834–0.950), sensitivity of 94%, and specificity of 92%, significantly outperforming conventional ADC (PGSE). Among 82 IDC patients, fin showed a strong correlation with the Ki-67 index (p < 0.001). The Ki-67 prediction model (fin + d-mean + ADC (OGSE33Hz)) yielded an AUC of 0.825 (95% CI 0.736–0.914), significantly outperforming individual parameters (p < 0.05). CONCLUSION: The td-dMRI-based technique effectively differentiated benign from malignant breast lesions and provided noninvasive prediction of Ki-67 status in IDC, offering valuable tools for clinical decision-making. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"653-665"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes of varied internal echo patterns in ultrasound imaging of breast lymphoma.","authors":"Yumi Kokubu, Tomo Osako, Takehiko Sakai, Yui Tomita, Chieko Kato, Yuri Maruoka, Masashi Akiya, Chikako Takahata, Takayuki Ueno, Kiyoshi Matsueda","doi":"10.1007/s12282-025-01820-5","DOIUrl":"10.1007/s12282-025-01820-5","url":null,"abstract":"<p><p>BACKGROUND: Ultrasound (US) imaging of breast lymphoma often reveals a variety of internal echo patterns, making differentiation from breast cancer challenging. This study aimed to correlate pathological findings with US imaging features of breast lymphoma to enhance biopsy accuracy and diagnostic precision. MATERIALS AND METHODS: We retrospectively analyzed 37 lesions (36 cases) with available US images and needle biopsy pathology specimens from breast lymphoma patients at our hospital between 2010 and 2021. The area ratios of tumor cells, mammary gland tissue, and adipose tissue in pathology specimens were compared with internal echo patterns on US. Additionally, we assessed US images during the healing process in cases with complete resolution following treatment. RESULTS: US identified 34 of 37 lesions (92%) as masses. Of these, 23 (68%) exhibited mixed internal echoes, while 11 (32%) were hypoechoic. Among the mixed echo lesions, 9 (27%) displayed a mixed hyper-to-hypoechoic pattern, and 14 (41%) showed a mixed iso-to-hypoechoic pattern. Pathological analysis revealed that the tumor cell median area ratio was highest in hypoechoic masses, mammary gland tissue median ratio was highest in mixed iso-to-hypoechoic masses, and adipose tissue median ratio was highest in mixed hyper-to-hypoechoic masses. During healing, the mass changed to non-mass abnormalities in 10 cases (77%) and decreased in size while retaining its shape in 3 cases (23%). CONCLUSION: The internal echo patterns of breast lymphoma varied depending on three factors: the proportion of tumor cells; the presence of regions with low tumor cell density; and adipose tissue infiltration. Hypoechoic areas likely reflected tumor cells, isoechoic areas mammary gland tissue, and hyperechoic areas adipose tissue infiltration. These findings suggest that biopsy from hypoechoic regions is recommended for accurate diagnosis. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"582-592"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of xeno-free induced mesenchymal stem/stromal cells in enhancing autologous fat graft survival.","authors":"Hideharu Nakamura, Takaya Makiguchi, Takahiro Yamaguchi, Sasagu Kurozumi, Daisuke Kamiya, Makoto Ikeya, Takaaki Fujii, Akihiko Uchiyama, Sei-Ichiro Motegi, Jun Horiguchi, Ken Shirabe, Satoshi Yokoo","doi":"10.1007/s12282-026-01838-3","DOIUrl":"10.1007/s12282-026-01838-3","url":null,"abstract":"<p><p>BACKGROUND: Breast reconstruction using autologous fat grafting offers a less invasive alternative with shorter surgical times compared to traditional flap procedures. Although adipose-derived stem cells (ASCs) have improved fat graft survival rates, the variability in mesenchymal stem cells (MSCs) quality due to donor health and medication intake poses challenges. MSCs derived from induced pluripotent stem cells (iPSC-MSCs) demonstrate enhanced proliferative and immunomodulatory properties that may further enhance outcomes. METHODS: We harvested human adipose tissue from surgical specimens and isolated ASCs. We used human iPSC-MSCs generated through a neural crest cell lineage under xeno-free conditions (iMSCs), to assess the improvement in survival and integration of autologous human adipose tissue grafts in BALB/c-nu/ + mice. We compared outcomes in groups treated with phosphate-buffered saline (PBS), ASCs, and iMSCs over 28 days, focusing on fat graft retention, fibrosis, and neovascularization, and adipogenic differentiation using vimentin/perilipin immunofluorescence staining. RESULTS: iMSC treatment significantly preserved graft area (82.3 ± 20.5%) compared to PBS controls (50.6 ± 28.7%) and ASC treatments (65.3 ± 24.7%). It also resulted in the lowest fibrosis (7,748.7 ± 6,018.6 µm2) and highest neovascularization (68,681.5 ± 21,363.4 µm2), indicating improved tissue integration and vascularization. The proportion of vimentin-positive/perilipin-positive cells—indicative of adipogenic differentiation—was significantly higher in the iMSC group (7.46%) compared to PBS (4.51%, p = 0.025). CONCLUSION: iMSCs may enhance fat graft survival through both paracrine signaling and adipogenic differentiation, supporting a dual mechanism of action. These findings highlight their potential as a standardized, high-performance cellular adjunct for improving surgical outcomes in breast reconstruction and potentially other regenerative medicine applications. Further studies incorporating cell tracking techniques are warranted to confirm the direct differentiation potential of iMSCs. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"612-624"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of peripheral myeloid-derived suppressor cells in advanced breast cancer.","authors":"Haruka Kanaoka, Masayuki Nagahashi, Junko Tsuchida, Mamiko Kuroiwa, Sayaka Urano, Miki Komatsu, Shoko Yoshida, Aoi Oshiro, Gen Sugimoto, Ayumu Mitsuyoshi, Yusa Togashi, Akira Hattori, Tomoko Higuchi, Arisa Nishimukai, Masafumi Shimoda, Yasuo Miyoshi","doi":"10.1007/s12282-026-01831-w","DOIUrl":"10.1007/s12282-026-01831-w","url":null,"abstract":"<p><p>BACKGROUND: The exact roles of myeloid-derived suppressor cells (MDSCs) and regulatory T cells in the peripheral blood of individuals with advanced breast cancer undergoing chemotherapy remain unclear. This study aimed to assess peripheral blood immune-related markers, including MDSCs, in patients with advanced breast cancer treated with chemotherapy, and to examine the relationship between these immune cells and clinical outcomes. We also examined the relationship between MDSCs and peripheral blood biomarkers, including the absolute lymphocyte count and neutrophil-to-lymphocyte ratio. METHODS: Seventy-three women who were treated with chemotherapy for advanced breast cancer were evaluated. Blood samples from patients at baseline and after cycle 1 treatment were subjected to flow cytometry. RESULTS: Individuals with a lower baseline level of MDSCs demonstrated a significantly longer progression-free survival (PFS) and a tendency for enhanced overall survival (OS) compared with those with a higher level of MDSCs. The baseline level of MDSCs was a significant independent prognostic factor for PFS. Patients with a low proportion of MDSCs after cycle 1 had significantly better PFS and OS than their counterparts. The group of patients with a low proportion of MDSCs at baseline and after cycle 1 showed significantly better PFS and OS than the other groups. Patients with a low absolute lymphocyte count, an elevated neutrophil-to-lymphocyte ratio, and a reduced lymphocyte-to-monocyte ratio exhibited significantly higher MDSC levels. CONCLUSIONS: The level of MDSCs may serve as a prognostic indicator for individuals with advanced breast cancer. Peripheral blood biomarkers may reflect the proportion of circulating MDSCs. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"601-611"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of HER2, HER3, and TROP2 in primary tumors and brain metastases of breast cancer.","authors":"S Kusuhara, T Kogawa, M Shimokawa, C Funasaka, C Kondoh, K Harano, N Matsubara, Y Naito, A Hosono, K Satomi, M Yoshida, S Fujii, T Onishi, A Suto, K Yonemori, K Koyama, R Nakamura, N Maeda, Y Narita, T Mukohara","doi":"10.1007/s12282-026-01841-8","DOIUrl":"10.1007/s12282-026-01841-8","url":null,"abstract":"<p><p>BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-directed antibody–drug conjugate (ADC) therapy has shown efficacy in HER2-positive breast cancer brain metastases. However, there is still an unmet medical need for further exploration of other suitable targets for ADCs in brain metastases (BMs). METHODS: The expression of HER2, HER3, and trophoblast surface antigen 2 (TROP2) was evaluated using immunohistochemistry (IHC) in pairs of primary tumors (PTs) and surgically resected BMs from 44 patients with breast cancer. Expression levels were classified as 0, 1 + , 2 + , or 3 + based on IHC intensity and the proportion of positive cells. RESULTS: The analysis revealed that HER3 and TROP2 expression (IHC ≥ 1 +) was observed in all but one BM specimen. TROP2 was highly expressed (IHC ≥ 2 +) in both BMs and PTs (86% and 70%, respectively; p = 0.11). High expression of HER3 was more frequent in BMs than in PTs (91% and PTs 59%, respectively; p < 0.01), regardless of breast cancer subtype. In individual paired samples, 95.5% (42/44) exhibited equal or higher HER3 expression in BMs than in PTs. In contrast, high HER2 expression (IHC ≥ 2 +) was observed in similar proportions between BMs and PTs (43% and 41%, respectively; p = 1.00). CONCLUSIONS: The observation of more frequent high-level expression of HER3 in BMs than in PTs, and high-level expression of TROP2 in both BMs and PTs suggests the potential of HER3- and TROP2-based ADC therapy for BMs from breast cancer. Further prospective studies are warranted to validate this hypothesis. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"644-652"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in re-excision rates after publication of guidelines defining positive margins for breast-conserving surgery: a collaborative study of the Japanese breast cancer society.","authors":"Takehiko Sakai, Yuri Kimura, Makoto Ishitobi, Atsushi Yoshida, Yasuaki Sagara, Yuka Ono, Koji Takada, Yuko Takahashi, Takahiro Tsukioki, Mao Kimoto, Tomo Osako","doi":"10.1007/s12282-026-01853-4","DOIUrl":"10.1007/s12282-026-01853-4","url":null,"abstract":"<p><p>BACKGROUND: The 2014 SSO-ASTRO consensus guidelines redefined a positive margin requiring re-excision after breast-conserving surgery (BCS) as “tumor on ink,” with several studies internationally demonstrating decreased re-excision rates thereafter. In Japan, this definition has been explicitly incorporated into the 2018 Japanese Breast Cancer Society (JBCS) guidelines; however, its impact on national clinical practice remains unclear. METHODS: We conducted a nationwide questionnaire survey of 521 JBCS-accredited institutions regarding BCS practices, imaging, surgery, margin assessment, and re-excision rates before and after 2018. In parallel, a multicenter retrospective cohort study from seven institutions analyzed positive margins and re-excision trends between 2008 and 2022. RESULTS: Overall, 262 institutions (response rate 55.7%) participated in the survey. Institutions reporting a positive margin rate of 0–10% increased from 47 to 63% in 2018. Institutions with a re-excision rate of 0–10% increased from 45 to 49%. In a cohort study of 18,688 BCS cases, positive margin rates fell from 11.2% (2008–14) to10.1% (2015–18) and 7.9% (2019–22), and re-excision rates from 7.6% to 6.6% and 4.9%. Multivariate analysis identified younger age, invasive lobular carcinoma, larger tumor size, lymph node positivity, and earlier surgical period as significant predictors of re-excision. CONCLUSIONS: This nationwide study demonstrates that the implementation of international and domestic guidelines has contributed to a significant yet gradual reduction in re-excision rates following BCS in Japan. These improvements reflect Japan's already-low positive margin and re-excision rates, which have been maintained through rigorous comprehensive margin assessment methodologies. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"761-769"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solamargin-functionalized gold nanoparticles codelivering photothermal-immunotherapy for triple-negative breast cancer.","authors":"Zhengwei Gui, Lu Zhao, Shiyang Liu, Lin Zhang","doi":"10.1007/s12282-026-01849-0","DOIUrl":"10.1007/s12282-026-01849-0","url":null,"abstract":"<p><p>BACKGROUND: The high rates of metastasis and recurrence in triple-negative breast cancer (TNBC) underscore the limitations of current therapies. Solamargin (SM), a bioactive glycoside, possesses potential antitumor activity, but its efficacy is limited by low potency and off-target effects. METHODS: We engineered Au@PEG-SM, a nanoconjugate designed for targeted delivery. Beyond traditional direct killing, we employed vascular endothelial cell models, STING-specific inhibitors (H-151), and cytokine neutralization assays to rigorously validate the molecular mechanism. Systemic immune profiling, including the analysis of lymph node dendritic cells, and bilateral tumor models were used to assess antitumor efficacy. RESULTS: Au@PEG-SM synergizes with photothermal therapy (PTT) to achieve a potent 1 plus 1 greater than 2 therapeutic effect. Mechanistically, low-dose SM sensitizes the cGAS-STING pathway in vascular endothelial cells; upon synergistic activation by PTT-released DNA, this triggers a massive secretion of IFN-β and TNF-α, leading to indirect tumor cell apoptosis. This process, combined with robust immunogenic cell death (ICD) and promoted dendritic cell maturation in lymph nodes, triggers a systemic antitumor response. Comprehensive immune profiling revealed that this combination therapy significantly increases the infiltration of NK cells and CD8 + T cells while markedly reducing immunosuppressive MDSCs and regulatory T cells (Tregs) in both primary and distant tumors. When combined with anti-PD-L1 blockade, the therapy eradicated primary tumors and established durable immune memory. CONCLUSIONS: This study establishes Au@PEG-SM as a powerful platform that achieves systemic immune activation via a sensitized STING-secretome-DC cascade. By providing rigorously validated mechanistic insights and a holistic immune landscape, our work offers a promising multimodal paradigm for overcoming TNBC. </p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":"705-721"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}