Breast Cancer Research and Treatment最新文献

{"title":"The cytokine profile correlates with less tumor-infiltrating lymphocytes in luminal A breast cancer.","authors":"Eri Ishikawa, Takahiro Watanabe, Takako Kihara, Mamiko Kuroiwa, Miki Komatsu, Sayaka Urano, Masayuki Nagahashi, Seiichi Hirota, Yasuo Miyoshi","doi":"10.1007/s10549-024-07492-7","DOIUrl":"https://doi.org/10.1007/s10549-024-07492-7","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor-infiltrating lymphocyte (TIL) levels are prognostic and predictive factors for breast cancer. Unlike other subtypes, most luminal A breast cancers are immune deserts; however, the underlying mechanisms are poorly understood.</p><p><strong>Methods: </strong>Immune-related cytokines, chemokines, and growth factors were measured in the sera of 103 patients with breast cancer using a multiplex panel. The TILs were evaluated for hotspot lesions.</p><p><strong>Results: </strong>Circulating interleukin 1 receptor antagonist (IL-1ra), IL-8, IL-12, IL-17, macrophage inflammatory protein-1β (MIP-1b), and platelet-derived growth factor B homodimer (PDGF-bb) concentrations were significantly associated with TIL levels. Cluster analysis using these six variables identified six clusters related to TIL levels. Breast cancers with high TILs (≥ 50%) were most frequent in cluster 3 (9 out of 15 cases, 60.0%), followed by cluster 1 (8 out of 34 cases, 23.5%), and the fewest in cluster 6 (1 out of 21 cases, 4.8%), whereas only one or three cases were present in clusters 2, 4, and 5 (p = 0.0064). Cluster 6, consisting mostly of luminal A (19 out of 21 cases, 90.5%), showed high levels of IL-12, IL-17, and PDGF-bb, and low levels of MIP-1b.</p><p><strong>Conclusion: </strong>We identified a luminal A-associated immunosuppressive cytokine signature in circulation. These results suggest that a tumor microenvironment with high levels of IL-17 and PDGF-bb, and low levels of MIP-1b in luminal A breast cancers results in low induction of TILs. Our data may partially explain the low TIL levels observed in the patients with luminal A breast cancer.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457996","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":"BAFF overexpression in triple-negative breast cancer promotes tumor growth by inducing IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses.","authors":"Zhuangwei Lv, Tian-Yun Wang, Yu Bi, Dandan Li, Qifei Wu, Baofeng Wang, Yunfeng Ma","doi":"10.1007/s10549-024-07504-6","DOIUrl":"https://doi.org/10.1007/s10549-024-07504-6","url":null,"abstract":"<p><strong>Purpose: </strong>Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment.</p><p><strong>Methods: </strong>BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion.</p><p><strong>Results: </strong>BAFF overexpression in 4T1 cells promoted tumor growth in vivo, suppressed CD8⁺ T cell activity, and increased IL-10-secreting CD5⁺ regulatory B cells in tumors. 4T1/BAFF cells directly enhanced IL-10 production in CD5⁺ B cells via BAFF/BAFF-receptor interactions, and IL-10 from CD5⁺ B cells inhibited IFN-γ secretion by T cells. B cell depletion partially reversed the tumor-promoting effects of BAFF overexpression. Our study reveals a novel mechanism by which BAFF can foster tumor progression, with the induction of IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses appearing to be a key component of BAFF's tumor-promoting activity.</p><p><strong>Conclusion: </strong>These findings underscore the complex immunomodulatory effects that BAFF exerts in the tumor microenvironment and point to BAFF-induced regulatory B cells as a potential new therapeutic target in breast cancer that warrants further investigation.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458005","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":"Trends in management and related outcomes for occult primary breast cancer.","authors":"M LaBella, R E Lile-King, C B Agala, P M Spanheimer, D W Ollila, K K Gallagher, J M Selfridge","doi":"10.1007/s10549-024-07500-w","DOIUrl":"https://doi.org/10.1007/s10549-024-07500-w","url":null,"abstract":"<p><strong>Purpose: </strong>Occult Primary Breast Cancer (OPBC) is a rare clinical condition in which breast cancer is located within the axillary lymph nodes, but no primary tumor is identified in the breast. We evaluated trends of neoadjuvant chemotherapy (NAC) use and subsequent axillary procedures in OPBC as well as outcomes for these patients.</p><p><strong>Methods: </strong>The National Cancer Database was used to identify adult women with cT0N1-3M0 breast cancer between 2012 to 2021 that underwent axillary lymph node surgery. Kaplan-Meier curves were used to evaluate survival between groups.</p><p><strong>Results: </strong>2759 patients met inclusion criteria. 86.2% underwent ALND alone in 2012, and this decreased to 65.6% in 2021. 4.7% underwent SLNB alone in 2012 and this increased to 16.2% in 2021 (p < 0.001). For patients who had undergone NAC, 46.4% of ALND patients had nodal pathologic complete response (nPCR), compared to 42.7% of SLNB + ALND and 66.4% of SLNB only patients. For patients with nPCR, there was no difference in overall survival (OS) between ALND, SLNB + ALND, and SLNB alone groups (p = 0.9912).</p><p><strong>Conclusion: </strong>Most OPBC patients were treated with ALND, with a modest increase towards SLNB use during the study period. There was no difference in OS with respect to axillary surgical procedure in our population for those with nPCR after NAC. This suggests that for carefully selected OPBC patients with an excellent clinical response to NAC and negative SLNB, omission of ALND may be considered.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457998","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":"APX2009 sensitizes hypoxic breast cancer cells to doxorubicin by increasing its accumulation and caspase-3/7-mediated apoptosis.","authors":"Ísis Salviano Soares de Amorim, Daphne Pinheiro, Matheus da Silva Oliveira, Mariana Moreno de Sousa Rodrigues, Julia Silva José, Priscyanne Barreto Siqueira, Bruno Ricardo Barreto Pires, Adenilson de Souza da Fonseca, Andre Luiz Mencalha","doi":"10.1007/s10549-024-07512-6","DOIUrl":"https://doi.org/10.1007/s10549-024-07512-6","url":null,"abstract":"<p><strong>Purpose: </strong>The association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia.</p><p><strong>Methods: </strong>The WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses.</p><p><strong>Results: </strong>MDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype.</p><p><strong>Conclusion: </strong>The findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457994","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":"BRCA promoter methylation in triple-negative breast cancer is preserved in xenograft models and represents a potential therapeutic marker for PARP inhibitors.","authors":"Kavitha Däster, Jürgen Hench, Maren Diepenbruck, Katrin Volkmann, Adelin Rouchon, Marta Palafox, Jorge Gomez Miragaya, Bogdan Tiberius Preca, Christian Kurzeder, Walter Paul Weber, Mohamed Bentires-Alj, Savas Deniz Soysal, Simone Muenst","doi":"10.1007/s10549-024-07502-8","DOIUrl":"https://doi.org/10.1007/s10549-024-07502-8","url":null,"abstract":"<p><strong>Purpose: </strong>Most triple-negative breast cancers (TNBC) are sporadic in nature and often associated with dysfunction of the BRCA1 or BRCA2 genes. Since somatic BRCA mutations are rare in breast cancer (BC), this dysfunction frequently is the result of BRCA promoter methylation. Despite the phenotypic similarities of these tumors to those with germline or somatic BRCA mutation, the evidence of response to PARP inhibitors is unclear.</p><p><strong>Methods: </strong>We analyzed the prevalence of BRCA promoter methylation in 29 BC metastases through the well-established Illumina Infinium EPIC Human Methylation Bead Chip. In cases with BRCA methylation, the xenograft of the same tumor was tested. Additionally, we compared BC xenografts with an identified BRCA methylation to their matched primary tumors and subsequently investigated the efficacy of PARP inhibitors on tumor organoids from a BRCA2 promoter-methylated BC.</p><p><strong>Results: </strong>BRCA2 promotor hypermethylation was identified in one pleural metastasis of a young patient as well as in the xenograft tissue. We also identified five more xenograft models with BRCA2 promotor hypermethylation. Analysis of one matched primary tumor confirmed the same BRCA2 methylation. PARP inhibitor treatment of tumor organoids derived from the BRCA2 methylated xenograft tumor tissue of the young patient showed a significant decline in cell viability, similar to organoids with somatic BRCA1 mutation, while having no effect on organoids with BRCA1 wildtype.</p><p><strong>Conclusion: </strong>BRCA promotor hypermethylation seems to be a rare event in metastatic BC but is preserved in subsequent xenograft models and might represent an attractive therapeutic marker for PARP inhibitors.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399380","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":"Uncovering novel pathogenic variants and pathway mutations in triple-negative breast cancer among the endogamous mizo tribe.","authors":"Lalawmpuii Pachuau, H Lalremmawia, Lalengkimi Ralte, Johan Vanlalpeka, Jeremy Lalrinsanga Pautu, Saia Chenkual, Thomas Zomuana, Sailo Tlau Lalruatfela, John Zohmingthanga, Lalchhandama Chhakchhuak, Ashok K Varma, Nachimuthu Senthil Kumar","doi":"10.1007/s10549-024-07501-9","DOIUrl":"https://doi.org/10.1007/s10549-024-07501-9","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of triple-negative breast cancer (TNBC) in India is higher compared to Western populations. The objective of this study is to identify novel and less reported variants in TNBC in Mizoram, a state with a high cancer incidence in India.</p><p><strong>Methods: </strong>We analysed whole exome sequencing data from triple-negative breast cancer (TNBC) patients in the Mizo population to identify key and novel variants. Moreover, we analysed reported breast cancer-related genes and pathway alterations.</p><p><strong>Results: </strong>Somatic mutation analysis revealed that TP53 was the most frequently mutated gene and TP53, CACNA1E, IGSF3, RYR1, and FAM155A as significantly mutated driver genes. Based on the ACMG guidelines, we identified a rare pathogenic germline variant of BRCA1 (p.C1697R) in 13% and a likely pathogenic frameshift insertion in RBMX (p.P106Ffs) in 73% of the patients. We also found that the ATM, STK11, and CDKN2A genes were significantly mutated in germline TNBC samples compared to healthy samples. Moreover, we identified novel somatic variants in CHEK2 (p.K182M) and NF1 (p.C245X), and novel germline variants RB1 (p.D111G), CDH1 (p.A10Gfs), CDKN2A (p.V96G), CDKN2A (p.S12Afs*22), MAP3K1 (CAAdelins0), MSH6 (p.L1226_L1230del), and PMS2 (TTCdelins0). Pathway analysis revealed that most somatic mutations were highly associated with PI3K-Akt signalling pathway and MAPK signalling pathways in TNBC.</p><p><strong>Conclusions: </strong>These findings identified novel variants and key genes contributing to disease development and progression. Further analysis of less studied genes, including RBMX, MRC1, ATM, CTNNB1, and CDKN2A, in TNBC may reveal new potential genes for targeted therapeutic strategies and contribute to clinical advancements in the treatment of TNBC.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387997","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":"Race and ethnicity and self-reported racial/ethnic discrimination in breast cancer patient interactions with providers in the Pathways Study.","authors":"Kevin R Bitsie, Thomas A Pearson, Marilyn L Kwan, Lusine Yaghjyan, Lisa Scarton, Salma Shariff-Marco, Lawrence H Kushi, Ting-Yuan David Cheng","doi":"10.1007/s10549-024-07499-0","DOIUrl":"10.1007/s10549-024-07499-0","url":null,"abstract":"<p><strong>Purpose: </strong>To examine the association of race and ethnicity groups with self-reported racial/ethnic discrimination in patient-provider interactions during the diagnosis and treatment for breast cancer.</p><p><strong>Methods: </strong>We analyzed data from the Pathways Study, a prospective cohort of women diagnosed with breast cancer from 2006-2013 in the Kaiser Permanente Northern California Health Care System. Racial/ethnic discrimination in patient-provider interactions was assessed with two questions from the Interpersonal Processes of Care survey at baseline and 6-months and 24-months post-diagnosis. Logistic regression was performed to compare women who self-identified as racial or ethnic minorities with Non-Hispanic White (NHW) women. Covariates included age at diagnosis, country of origin, education level, income, marital status, and medical provider's race/ethnicity.</p><p><strong>Results: </strong>Our sample included 1836 participants: 1350 NHW women and 486 women (87 Black, 208 Asian American, 153 Hispanic, 38 American Indian/Alaskan Native/Pacific Islander [AIANPI]) from racial or ethnic minority groups. In multivariate analysis, minority women were more likely to report racial/ethnic discrimination in patient-provider interactions than NHW women (adjusted odds ratio [aOR]: 4.73; 95% confidence interval [CI] 3.45-6.50). Specifically, Black women were most likely to self-report racial/ethnic discrimination in patient-provider interactions (aOR: 9.65; 95% CI 5.92-15.70), followed by Asian (aOR: 5.39; 95% CI 3.46-8.40), Hispanic (aOR: 2.55; 95% CI 1.54-4.14), and AIANPI (aOR: 1.74; 95% CI 0.58-4.25) women, compared with NHW women.</p><p><strong>Conclusion: </strong>Racial/ethnic discrimination was more likely self-reported from minority women diagnosed with breast cancer. Additional studies are needed to understand the mechanisms and impact of racial/ethnic discrimination in patient-provider interactions on disparities.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379097","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":"Intracranial outcomes following neurosurgical resection in patients with brain metastases secondary to HER2-positive breast cancer versus other subtypes.","authors":"Narmeen S Rashid, Nayan Lamba, Paul J Catalano, Wenya Linda Bi, Omar Arnaout, Shyam K Tanguturi, Rifaquat Rahman, Daphne A Haas-Kogan, Nancy U Lin, Patrick Y Wen, Ayal A Aizer","doi":"10.1007/s10549-024-07493-6","DOIUrl":"https://doi.org/10.1007/s10549-024-07493-6","url":null,"abstract":"<p><strong>Purpose: </strong>Neurosurgical resection serves an important role in select patients with breast cancer and brain metastases but can delay systemic therapy and yield complications. Consequently, identification of patients most likely to benefit from surgery is important. Given the poorer long-term intracranial responses to radiotherapy sometimes observed in HER2-positive (HER2 +) patients, we investigated whether neurosurgical resection is differentially beneficial in this population.</p><p><strong>Methods: </strong>We identified 633 patients with newly diagnosed brain metastases arising from breast cancer managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2010 and 2022. Patients were stratified by breast cancer subtype: HER2 + (N = 189), hormone receptor positive (HR +)/HER2- (N = 267), and triple negative (N = 177). Per-patient and per-metastasis outcomes were evaluated; interaction models assessing the impact of neurosurgical resection by subtype were constructed.</p><p><strong>Results: </strong>Relative to HR + /HER2- subtype, omission of upfront neurosurgical resection in patients with HER2 + disease was associated with increased subsequent utilization of salvage stereotactic radiation, whole brain radiotherapy, and craniotomy (interaction HR 2.02 [95% CI, 1.04-3.93], p = 0.04; HR 3.92 [95% CI, 1.24-12.40], p = 0.02; HR 4.98 [95% CI, 1.34-18.58], p = 0.02, respectively). Tumors stemming from HER2 + versus HR + /HER2- primaries displayed increased local recurrence when upfront neurosurgical resection was omitted (interaction HR 3.62 [95% CI, 1.06-12.38], p = 0.04). No such associations were noted when comparing triple negative to HR + /HER2- subtype (p-interaction > 0.05 in all cases).</p><p><strong>Conclusion: </strong>Patients with HER2 + disease and brain metastases may disproportionately benefit from upfront neurosurgical resection relative to other subtypes. If validated, our results may suggest a lower threshold to consider surgery in brain metastases secondary to HER2 + breast cancer.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379096","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":"Irish national real-world analysis of the clinical and economic impact of 21-gene oncotype DX® testing in early-stage, 1-3 lymph node-positive, oestrogen receptor-positive, HER2-negative, breast cancer.","authors":"I M Browne, R A McLaughlin, C S Weadick, S O'Sullivan, L M McSorley, D K Hadi, S J Millen, M J Higgins, J P Crown, R S Prichard, D P McCartan, A Dk Hill, R M Connolly, S A Noonan, D O'Mahony, C Murray, C O'Hanlon-Brown, B T Hennessy, C M Quinn, C M Kelly, S O'Reilly, P G Morris, J M Walshe","doi":"10.1007/s10549-024-07486-5","DOIUrl":"https://doi.org/10.1007/s10549-024-07486-5","url":null,"abstract":"<p><strong>Purpose: </strong>The treatment landscape of Oestrogen receptor-positive (ER-positive) breast cancer is evolving, with declining chemotherapy use as a result of Oncotype DX Breast Recurrence Score® testing. Results from the SWOG S1007 RxPONDER trial suggest that adjuvant chemotherapy may benefit some premenopausal women with ER-positive, HER2-negative disease with 1-3 positive lymph nodes (N1), and a Recurrence Score® (RS) of ≤ 25. Postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. We examine the clinical and economic impact of Oncotype DX® testing on treatment decisions in patients with N1 disease in Ireland using real world data.</p><p><strong>Methods: </strong>From March 2011 to October 2022, a retrospective, cross-sectional observational study was performed of patients with ER-positive, HER2-negative N1 breast cancer, who had Oncotype DX testing across 5 of Ireland's largest cancer centres. Patients were classified into low risk (RS 0-13), intermediate risk (RS 14-25) and high risk (RS > 25). Data were collected via electronic patient records. Information regarding costing was provided primarily by pre-published sources.</p><p><strong>Results: </strong>A total of 828 N1 patients were included in this study. Post Oncotype DX testing, 480 patients (58%) were spared chemotherapy. Of the patients who had a change in chemotherapy recommendation based on Oncotype DX testing, 271 (56%), 205 (43%), 4 (1%) had a RS result of 0-13, 14-25 and > 25 respectively. Use of Oncotype DX testing was associated with a 58% reduction in chemotherapy administration overall. This resulted in estimated savings of over €6 million in treatment costs. Deducting the assay cost, estimated net savings of over €3.3 million were achieved. Changes in the ordering demographics of Oncotype DX tests were identified after RxPONDER data were presented, with increased testing in women ≥ 50 years and a reduction in proportion of tests ordered for women < 50 years.</p><p><strong>Conclusion: </strong>Between 2011 and 2022, assay use resulted in a 58% reduction in chemotherapy administration and net savings of over €3.3 million.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370989","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 of a novel prediction model for carriage of BRCA1/2 pathogenic variant in Japanese patients with breast cancer based on Japanese organization of hereditary breast and ovarian cancer registry data.","authors":"Nana Komatsu, Takashi Chishima, Chie Watanabe, Kanae Taruno, Mayuko Inuzuka, Masanori Oshi, Masami Arai, Seigo Nakamura","doi":"10.1007/s10549-024-07485-6","DOIUrl":"10.1007/s10549-024-07485-6","url":null,"abstract":"<p><strong>Purpose: </strong>With the increasing demand for BRCA genetic testing, most existing prediction models were developed using data from individuals of European descent. This study aimed to identify clinicopathological factors of hereditary breast and ovarian cancer (HBOC) syndrome and develop the first Japanese-specific prediction model for BRCA pathogenic variant carriers in Japan.</p><p><strong>Methods: </strong>We utilized data from 3072 Japanese patients with breast cancer aggregated by the Japanese Organization of Hereditary Breast and Ovarian Cancer registry. Prediction models were developed using 70% of the overall dataset and validated using the remaining 30%. Factors associated with the BRCA pathogenic variant status were identified using logistic univariate analysis, and significant factors were further analyzed using logistic multivariate analysis to develop prediction models for BRCA1/2 (BRCA1 and/or BRCA2), BRCA1, and BRCA2 pathogenic variants.</p><p><strong>Results: </strong>BRCA1 showed associations with aggressive clinicopathological factors such as triple-negative breast cancer and nuclear grade 3. Moreover, the prediction model showed a high area under the curve (AUC) of 0.879. By contrast, BRCA2 exhibited fewer characteristic associated factors, and the AUC of the model was 0.669. Common factors shared by BRCA1/2, BRCA1, and BRCA2 were the age at diagnosis of breast cancer and the youngest age of relatives with breast cancer. Consistent with previous research, early-onset breast cancer appeared to be strongly associated with HBOC.</p><p><strong>Conclusion: </strong>We successfully developed prediction models for BRCA1/2, BRCA1, and BRCA2 pathogenic variants. By accurately stratifying patients' risk and guiding targeted screening and preventative interventions, these models will contribute to improved management and outcomes of HBOC.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361064","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}