Breast Cancer Research and Treatment最新文献

{"title":"The natural history of ductal carcinoma in situ: development, validation, and estimated outcomes of the SimDCIS model.","authors":"Keris Poelhekken, Monique D Dorrius, Amanda Dibden, Stephen W Duffy, Bert van der Vegt, Geertruida H de Bock, Marcel J W Greuter","doi":"10.1007/s10549-025-07639-0","DOIUrl":"10.1007/s10549-025-07639-0","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a novel simulation model for ductal carcinoma in situ (DCIS), fully validate it, and provide new estimates for DCIS in the setting of population-based biennial screening.</p><p><strong>Methods: </strong>A micro-simulation Markov model for DCIS (SimDCIS) was developed. Input parameters were independently derived from the literature and transition parameters were age- and grade-dependent. The model was applied to the Dutch biennial screening program. SimDCIS was internally, cross, and externally validated by comparison of the model output to data from the Netherlands Cancer Registry, a modelling study on the United Kingdom Frequency Trial, and the United Kingdom screening program, respectively. Univariate and probabilistic sensitivity analyses were performed to estimate uncertainty. DCIS regression, progression to invasive breast cancer (IBC), clinical detection, and screen-detection were estimated in Dutch screening setting.</p><p><strong>Results: </strong>SimDCIS matched observed data in internal, external, and cross-validation. The model was most sensitive to DCIS onset probability, and the maximum variation in screen-detection rate was 11%. In Dutch screening setting, DCIS regression, progression to IBC, clinical detection, and screen-detection were estimated at 8% (0-14%), 19% (16-24%), 8% (0-13%), and 61% (56-65%), respectively. Grade distribution was 20% grade 1, 38% grade 2, and 42% grade 3.</p><p><strong>Conclusion: </strong>SimDCIS provides strong accuracy across validation methods and is particularly sensitive to DCIS onset probability. Most DCIS will be found through screening, of which less than 50% of DCIS will be grade 3, less than 1 in 10 will regress, and 1 out of 5 DCIS will progress to IBC in biennial screening setting.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"223-231"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530851","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":"Outcomes of the Saudi breast cancer early detection program: a nine-year analysis (2012-2020).","authors":"Salman M Albeshan, Maha M Almuqbil, Mahoud M Elsharkawi, Hifa Nassri, Nuha A Khoumais","doi":"10.1007/s10549-025-07633-6","DOIUrl":"10.1007/s10549-025-07633-6","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to report the preliminary outcome of the Saudi breast cancer early detection program (SBCEDP).</p><p><strong>Methods: </strong>Mammography screens were done for Saudi women (age 40-69 years old) who participated in the SBCEDP from April 2012 to December 2020. Independent double-blind reading of the mammograms was performed by two radiologists. Analysis of age at diagnosis, cancer characteristics, and available screening indicators will be reported within this timeframe.</p><p><strong>Results: </strong>Among 72,774 screened women, 504 had breast cancer cases, yielding a cancer detection rate of 6.93 per 1000 screened women. DCIS detection rate was 0.87 per1000 screened women (n = 63). Mean age at diagnosis was 53.61 years (SD = 8.85) and the majority women had fatty breast tissue (A and B, 65%). Luminal A subtype was predominant (N = 58.6%), whereas triple-negative breast cancers constituted about 12.6% of cases. Estrogen and progesterone positivity was common (more than 65% of cases). Early and localized breast cancer was reported among 28% and 45.8% of women, respectively. Lesions mean size was 23.88 mm and mastectomy rate was 54.2%.</p><p><strong>Conclusion: </strong>Although not all screening indicators were available, the SBCEDP demonstrates encouraging results, with notable rates of early-stage diagnosis. Continuous evaluation and improvement of screening strategies are essential for further enhancing the program effectiveness in reducing breast cancer mortality and morbidity among Saudi women.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"185-193"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413334","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":"Did the COVID-19 consortium recommendations impact the treatment of breast cancer during the COVID-19 pandemic?","authors":"Marie L Fefferman, Kelley Chan, Joseph Cotler, Danielle M Thompson, Richard J Bleicher, Scott H Kurtzman, Jill M Dietz, Katharine Yao","doi":"10.1007/s10549-025-07617-6","DOIUrl":"10.1007/s10549-025-07617-6","url":null,"abstract":"<p><strong>Purpose: </strong>We examined the impact of the COVID-19 consortium recommendations on the surgical management of breast cancer during the first year of the pandemic.</p><p><strong>Methods: </strong>Patients with newly diagnosed ER + DCIS, ER- DCIS, AJCC Stage cT1-2N0-1 ER + , HER2-, HER2 + , and triple negative breast cancer were identified from the National Cancer Database from 2018 to 2021. An interrupted time series design evaluated differences in surgical delay and use of neoadjuvant chemotherapy/immunotherapy (NAC) and endocrine therapy (NET) before and after the pandemic.</p><p><strong>Results: </strong>A total of 895116 female patients were included in the study with a mean age of 61.7 years. Time to surgery decreased by an average 5.5 days from January 2020 to May 2020 for all breast cancer types, corresponding with a 62.2% decrease in breast cancer diagnoses per month from January 2020 to April 2020. The use of NET increased from 5.6 to 23.6% from January to March 2020 for patients with ER + DCIS and 8.0 to 31.1% for ER + cT1-2N0 cancer (both p < 0.01). The use of NAC for HER2 + tumors and triple negative breast cancers has been increasing since 2018 and a larger than expected increase was seen from 57.2 to 63.6% for HER2 + tumors and 55.6 to 68.7% for triple negative breast cancers (both p < 0.01). Treatment practices returned to pre-pandemic levels in June 2020.</p><p><strong>Conclusion: </strong>Prior to the publication of the Consortium recommendations, time to surgery decreased while the use of NET and NAC increased, with the resumption of pre-pandemic practices by June 2020.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"11-22"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045555","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":"Pathologic complete response rates of patients with ER-low/HER2-negative breast cancer treated with neoadjuvant pembrolizumab plus chemotherapy in the neo-real study.","authors":"Renata Colombo Bonadio, Monique Celeste Tavares, Flávia Cavalcanti Balint, Isadora Martins de Sousa, Ana Carolina Marin Comini, Fernanda Madasi, Jose Bines, Rafael Dal Ponte Ferreira, Daniela Dornelles Rosa, Candice Lima Santos, Zenaide Silva de Souza, Daniele Assad-Suzuki, Júlio Antônio Pereira de Araújo, Débora de Melo Gagliato, Carlos Henrique Dos Anjos, Bruna M Zucchetti, Anezka Ferrari, Mayana Lopes de Brito, Renata Cangussu, Maria Marcela Fernandes Monteiro, Paulo M Hoff, Laura Testa, Maria Del Pilar Estevez-Diz, Romualdo Barroso-Sousa","doi":"10.1007/s10549-025-07628-3","DOIUrl":"10.1007/s10549-025-07628-3","url":null,"abstract":"<p><strong>Purpose: </strong>Estrogen receptor-low (ER-low) breast cancer (BC) present clinicopathological features and disease behavior resembling triple-negative breast cancer, but have been frequently excluded from pivotal trials designed for the latter. Since neoadjuvant pembrolizumab plus chemotherapy (P + CT) is the new standard of care for stage II-III triple-negative breast cancer (TNBC), we aimed to access the effectiveness of this therapy for ER-low tumors.</p><p><strong>Methods: </strong>We evaluated patients with ER-low BC included in the Neo-Real/ GBECAM-0123 study, a real-world data study evaluating patients treated with neoadjuvant P + CT since July 2020 across ten cancer centers. The objective of this study was to evaluate the effectiveness of neoadjuvant P + CT through pathologic complete response (pCR).</p><p><strong>Results: </strong>Twenty patients were included in this analysis. Median age was 40 years (range 28-64). Most patients had grade 3 tumors (n = 18, 90%), with a median Ki67 index of 75% (range 30-95%), and 70% had stage II tumors. All the twenty patients were submitted to surgery, with a pCR observed in 12 cases (pCR rate of 60%). Receiving less than 6 cycles of pembrolizumab was associated with a trend towards worse pCR rates (20% vs 73.3%).</p><p><strong>Conclusions: </strong>The clinicopathological features and the response to neoadjuvant P + CT observed in this ER-low BC cohort are similar to that observed in TNBC. Patients with stage II-III ER-low/HER2- BC should be treated with neoadjuvant P + CT following the treatment standards for TNBC, and proper adherence to the regimen is relevant to improve effectiveness.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"131-137"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078238","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":"Lumpectomy surgery for large ductal carcinoma in situ.","authors":"Daniela Bresciani Padilla, Jacqueline Tsai, Amanda Sutherland Beck, Irene L Wapnir","doi":"10.1007/s10549-025-07621-w","DOIUrl":"10.1007/s10549-025-07621-w","url":null,"abstract":"<p><strong>Purpose: </strong>Breast-conserving surgery for larger ductal carcinoma in situ (DCIS) remains limited. We compare the attempted use and success rates of lumpectomy surgery in patients with DCIS measuring ≥ 4 cm versus < 4 cm.</p><p><strong>Methods: </strong>A retrospective review was conducted using the institutional tumor registry to identify cases of pure DCIS that were surgically treated from 2015 to 2022. Clinical-pathological data were abstracted from electronic medical records. Pathologic tumor size on initial surgery was used to define the two cohorts. Comparisons of variables were made using Chi-square and ANOVA tests.</p><p><strong>Results: </strong>A total of 669 patients, 84% (562) with tumors measuring < 4 cm and 16% (107) ≥ 4 cm were identified. Lumpectomy was the initial surgery performed for 89% of women with lesions measuring < 4 cm on preoperative imaging studies compared to 64% of those ≥ 4 cm. Overall, 461 (92.9%) of 496 in the < 4 cm succeeded at lumpectomy compared to 36 (56.3%) of 64 in the ≥ 4 cm group. Re-excision lumpectomies or mastectomy were performed in 27% and 44% of the < 4 cm and ≥ 4 cm subgroups. Lumpectomy was achieved for 70% of women with tumors in the 4 to 5.9 cm range compared to 33% in the 6-7.9 cm and the ≥ 8 cm groups. There were no local recurrences in the ≥ 4 cm group at an average of 4.4 years follow-up.</p><p><strong>Conclusion: </strong>Lumpectomy is a viable option for many patients with DCIS ≥ 4 cm, especially those measuring < 6 cm, though repeat re-excisions may be required after initial attempt.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"51-58"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381424","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":"Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial.","authors":"Wonyoung Jung, Rebecca A Hubbard, Amanda M Smith, Kyunga Ko, Anran Huang, Jessica Wang, Jordan M Isaacs, Liyong Zhang, Peter P Liu, Zhen Chen, Payal D Shah, David Mintzer, Saveri Bhattacharya, Hayley M Knollman, Amy S Clark, Daniel Koropeckyj-Cox, Melissa Messinger, Nicholas S Wilcox, Congying Xia, Vivek Narayan, Jenica N Upshaw, Saro H Armenian, Bonnie Ky","doi":"10.1007/s10549-025-07636-3","DOIUrl":"https://doi.org/10.1007/s10549-025-07636-3","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer treatment results in increased cardiotoxicity risk; a risk-guided approach to cardioprotection has not been fully tested.</p><p><strong>Methods: </strong>This single-center, randomized Phase I trial enrolled patients with Stage I-III breast cancer who planned to receive anthracycline and/or trastuzumab therapy. An internally validated cardiotoxicity risk score classified participants as low or elevated risk. Elevated risk participants were randomized to receive open-label carvedilol or usual care for 12 months, beginning at cancer therapy initiation. Study visits occurred at baseline, 3, 6, 9, 12, and 24 months. Primary outcomes included feasibility, safety, and tolerability. Exploratory outcomes included echocardiography, biologic, and patient-reported measures.</p><p><strong>Results: </strong>Of the 166 eligible patients approached, 68 (41%) agreed to participate and ultimately enrolled. Among these participants (median age 52, 35% Black), 49 were classified as low and 19 elevated risk. Within the elevated risk group, 13 were randomized to carvedilol and 6 usual care. For those randomized to carvedilol, the median maximum dose was 6.25 mg twice daily, with 93% adherence. Adverse events of interest (grade 3 + bradycardia, hypotension, or fatigue) occurred in 9% with carvedilol, 13% in usual care, and 4% in low risk groups. One (1.5%) low risk participant experienced cardiac dysfunction. There were no substantial differences in secondary outcomes across groups. The participant withdrawal rate was 7%.</p><p><strong>Conclusions: </strong>This Phase 1 trial demonstrates that a risk-guided strategy can be applied to patients with active cancer. However, additional strategies are necessary to optimize the design and execution of non-treatment intervention trials in patients with active cancer.</p><p><strong>Trial registration: </strong>NCT04023110.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762833","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":"Education and mammographic breast density.","authors":"Syed Mahfuz Al Hasan, Kayode A Matthew, Adetunji T Toriola","doi":"10.1007/s10549-024-07575-5","DOIUrl":"10.1007/s10549-024-07575-5","url":null,"abstract":"<p><strong>Purpose: </strong>There are conflicting reports on the associations of education with mammographic breast density (MBD). To address this, we investigated the associations of education with MBD and additionally determined if and to what extent this association is mediated by known confounders such as age and adiposity.</p><p><strong>Methods: </strong>Women (n = 1155) were recruited during their annual screening mammogram at the Joanne Knight Breast Health Center at Washington University School of Medicine in St. Louis, MO. We assessed MBD using volumetric percent density (VPD; Volpara 1.5; Volpara Health^®). We performed generalized linear modeling adjusted for potential confounders to estimate the differences in VPD by education level and evaluated whether associations differ by race and menopausal status. We also performed mediation analysis using PROCESS macro version 4.3. VPD was log-transformed, and back-transformed values are reported.</p><p><strong>Results: </strong>Women with college (n = 401) and postgraduate education (n = 396) had higher VPD (7.21% [95% CI 6.87-7.59] and 7.18% [95% CI 6.82-7.53], respectively) compared to women (n = 358) with below college education (6.62% [95% CI 6.27-7.00]; p = 0.051) in analysis adjusted for age, body mass index (BMI) and other confounders. However, the association attenuated when the analysis was adjusted for body fat% instead of BMI (college graduate: 7.26% [95% CI 6.92-7.62]; postgraduate: 7.19% [95% CI 6.85-7.55] vs. below college: 6.78% [95% CI 6.41-7.16]; p = 0.156). Body fat% and BMI mediated 71% and 64% of the association between education and VPD, respectively in premenopausal women, but not in postmenopausal women. Associations did not differ by race.</p><p><strong>Conclusion: </strong>Education was not associated with VPD after adjusting for adiposity. Adiposity mostly mediated the association between education and VPD, particularly among premenopausal women with body fat% a slightly more robust capture of adiposity than BMI.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"377-384"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833895","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":"Intraductal laser ablation during ductoscopy in patients with pathological nipple discharge.","authors":"Seher Makineli, Menno R Vriens, Paul J van Diest, Arjen J Witkamp","doi":"10.1007/s10549-024-07568-4","DOIUrl":"10.1007/s10549-024-07568-4","url":null,"abstract":"<p><strong>Background: </strong>Ductoscopy is a minimally invasive micro-endoscopic approach for direct visualization and removal of intraductal lesions of the breast. A challenge of ductoscopy is an adequate treatment of intraductal lesions by complete removal to prevent exploratory duct excision surgery. This study aimed to determine the in vivo feasibility of intraductal laser ablation during ductoscopy to remove intraductal lesions in patients suffering from pathological nipple discharge (PND).</p><p><strong>Methods: </strong>A prospective, single-center diagnostic feasibility trial was conducted between October 2022 and November 2023, enrolling adult women with unilateral PND and no radiological suspicion of malignancy. Intraductal laser ablation was performed after incomplete intraductal biopsy using a Thulium laser.</p><p><strong>Results: </strong>Duct cannulation and subsequent ductoscopic exploration were successful in 21 patients revealing an intraductal lesion in 13 patients (61.9%). From these 13 patients, 9 patients (69.2%) underwent intraductal laser ablation due to a residual lesion after biopsy. Pathology of the removed intraductal lesions showed a papilloma in eight (88.9%) patients and a papilloma/DCIS combination in one patient (11.1%). Post-procedure, PND stopped in 77.8% of the patients (7/9). Two patients had recurrent PND complaints caused by a residual lesion.</p><p><strong>Conclusion: </strong>Intraductal laser ablation during ductoscopy in patients with papillary lesions seems to be feasible and safe. The Thulium laser enables ablation of residual lesions and is therefore suitable for an immediate second intervention after ductoscopic removal of intraductal lesions. Further refinement and validation in a follow-up clinical trial are necessary to further assess its therapeutic efficacy.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"329-335"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187768","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":"The impact of cardiovascular risk factors on cancer progression: a prospective study in female breast cancer survivors.","authors":"Xinyi Feng, Zhengyi Deng, Michelle S McCullough, Betty J May, Erica Selznick, Jennifer Y Sheng, Avonne E Connor, Deborah K Armstrong, Kala Visvanathan","doi":"10.1007/s10549-025-07611-y","DOIUrl":"10.1007/s10549-025-07611-y","url":null,"abstract":"<p><strong>Purpose: </strong>To examine the effect of selected cardiovascular disease (CVD) risk factors over time on early cancer outcomes in breast cancer (BC) survivors.</p><p><strong>Methods: </strong>A prospective study was conducted among women aged 20-65 years with an incident invasive BC enrolled in the Breast and Ovarian Surveillance Service (BOSS) Cohort between 2005 and 2013. CVD risk based on selected risk factors was assessed at baseline and two follow-ups. Participants were categorized into low, medium, and high-risk groups. The primary outcome was BC recurrence (distant or local) or second primary cancer (SPC). Kaplan-Meier failure curves and multivariable Cox proportional hazard models were performed to compare the hazards across CVD risk score groups.</p><p><strong>Results: </strong>A total of 212 women with invasive BC contributed to 2211 person-years (median follow-up 11.7 years), 103 had low, 73 medium, and 36 high CVD risk scores at baseline. In multivariable analyses, BC survivors with medium CVD risk score had 2.09 times higher risk (95%CI = 1.09-4.02; p = 0.027) of recurrence/SPC compared to survivors with low CVD risk score. This association was particularly pronounced in postmenopausal women, those with estrogen receptor-positive BC, regional disease, or newly diagnosed BC. After excluding women taking cardiac medications, a higher risk of recurrence/SPC was also observed among those in the high-CVD-risk-score group, although not significant.</p><p><strong>Conclusion: </strong>Higher CVD risk score based on selected risk factors was significantly associated with BC recurrence or SPC, particularly in certain subgroups. Monitoring and treating a combination of CVD risk factors in BC survivors may help reduce BC progression.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"737-748"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381494","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":"Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263.","authors":"Nazan Gökşen Tosun, Özlem Kaplan","doi":"10.1007/s10549-024-07587-1","DOIUrl":"10.1007/s10549-024-07587-1","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"493-506"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944672","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}