NPJ Breast Cancer最新文献

{"title":"Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study).","authors":"Alex Schick, Sara Hardy, Myla Strawderman, Dandan Zheng, Michael Cummings, Michael T Milano, Allison Magnuson, Jacqueline Behr, Sarah Sammons, Kenneth Usuki, Nimish Mohile, Ruth O'Regan, Carey K Anders, David Hicks, Ajay Dhakal","doi":"10.1038/s41523-024-00673-z","DOIUrl":"10.1038/s41523-024-00673-z","url":null,"abstract":"<p><p>The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46-6.83, p = 0.0034; LM2: 5.32, 2.33-12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98-9.12, p = 0.0002; LM2: 7.40, 3.10-17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"69"},"PeriodicalIF":6.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study.","authors":"Simone Scagnoli, Simona Pisegna, Angela Toss, Roberta Caputo, Michelino De Laurentiis, Michela Palleschi, Ugo de Giorgi, Enrico Cortesi, Agnese Fabbri, Alessandra Fabi, Ida Paris, Armando Orlandi, Giuseppe Curigliano, Carmen Criscitiello, Ornella Garrone, Gianluca Tomasello, Giuliana D'Auria, Patrizia Vici, Enrico Ricevuto, Federica Domati, Claudia Piombino, Sara Parola, Roberta Scafetta, Alessio Cirillo, Beatrice Taurelli Salimbeni, Francesca Sofia Di Lisa, Lidia Strigari, Robert Preissner, Maurizio Simmaco, Daniele Santini, Paolo Marchetti, Andrea Botticelli","doi":"10.1038/s41523-024-00682-y","DOIUrl":"10.1038/s41523-024-00682-y","url":null,"abstract":"","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"68"},"PeriodicalIF":6.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen levels in young women with hormone receptor-positive breast cancer on ovarian function suppression therapy.","authors":"Megan E Tesch, Yue Zheng, Shoshana M Rosenberg, Philip D Poorvu, Kathryn J Ruddy, Rulla Tamimi, Lidia Schapira, Jeffrey Peppercorn, Virginia Borges, Steven E Come, Craig Snow, Shalender Bhasin, Ann H Partridge","doi":"10.1038/s41523-024-00680-0","DOIUrl":"10.1038/s41523-024-00680-0","url":null,"abstract":"<p><p>Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"67"},"PeriodicalIF":6.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer.","authors":"Volker Möbus, Hans-Joachim Lück, Ekkehart Ladda, Peter Klare, Knut Engels, Marcus Schmidt, Andreas Schneeweiss, Eva-Maria Grischke, Grischa Wachsmann, Helmut Forstbauer, Michael Untch, Frederik Marmé, Jens-Uwe Blohmer, Christian Jackisch, Jens Huober, Elmar Stickeler, Mattea Reinisch, Theresa Link, Bruno Sinn, Wolfgang Janni, Carsten Denkert, Sabine Seiler, Christine Solbach, Sabine Schmatloch, Julia Rey, Sibylle Loibl","doi":"10.1038/s41523-024-00675-x","DOIUrl":"10.1038/s41523-024-00675-x","url":null,"abstract":"<p><p>GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment. At median follow-up of 6.5 years (overall cohort) and 5.7 years (neoadjuvant cohort, N = 593), both regimens showed comparable 5-year OS rates (iddEnPC 90.8%, dtEC-dtD 90.0%, p = 0.320). In the neoadjuvant setting, iddEnPC yielded a higher pCR rate than dtEC-dtD (51.2% vs. 42.6%, p = 0.045). Patients achieving pCR had significantly improved 5-year iDFS (88.7% vs. 70.1%, HR 0.33, p < 0.001) and OS rates (93.9% vs. 83.1%, HR 0.32, p < 0.001), but OS outcomes were comparable regardless of pCR status. Thus, iddEnPC demonstrates superior pCR rates compared to dtEC-dtD, yet with comparable survival outcomes.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"66"},"PeriodicalIF":6.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer.","authors":"Gayathri R Devi, Pritha Pai, Seayoung Lee, Matthew W Foster, Dorababu S Sannareddy, Francois Bertucci, Naoto Ueno, Steven Van Laere","doi":"10.1038/s41523-024-00664-0","DOIUrl":"10.1038/s41523-024-00664-0","url":null,"abstract":"<p><p>Therapeutic resistance presents a significant hurdle in combating inflammatory breast cancer (IBC), adding to the complexity of its management. To investigate these mechanisms, we conducted a comprehensive analysis using transcriptomic and proteomic profiling in a preclinical model alone with correlates of treatment response in IBC patients. This included SUM149 cell lines derived from treatment-naïve patients, along with acquired drug resistance (rSUM149) and others in a state of resistance reversal (rrSUM149), aiming to uncover drug resistance networks. We identified specific ribosomal proteins associated with acquiring resistance. These correlated with elevated levels of molecular markers such as pERK, CDK1, XIAP, and SOD2. While resistance reversal in rrSUM149 cells largely normalized the expression profile, VIPER analysis revealed persistent alterations in ribosomal process-related proteins (AGO2, Exportin 1, RPL5), suggesting their continued involvement in drug resistance. Moreover, genes linked to ribosomal processes were significantly enriched (P < 0.001) among overexpressed genes in IBC patients (n = 87) who exhibited a pathological complete response (pCR) to neoadjuvant chemotherapy. Given the common hyperactivation of MAPK in IBC tumors, including rSUM149, we evaluated Merestinib, a multikinase inhibitor in clinical trials. It effectively targeted pERK and peIF4E pathways, suppressed downstream targets, induced cell death in drug-resistant rSUM149 cells, and showed synergistic effects with another tyrosine kinase inhibitor (Lapatinib) in parental cells. This underscores its significant impact on protein synthesis signaling, crucial for combating translational dependence in cancer cells. In summary, our study elucidates adaptive changes in IBC cells in response to therapy and treatment pauses, guiding precision medicine approaches for this challenging cancer type.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"65"},"PeriodicalIF":6.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of structural variants in early breast cancer patients","authors":"Ji-Yeon Kim, Kyunghee Park, Woong-Yang Park, Jin Seok Ahn, Young-Hyuck Im, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jonghan Yu, Yeon Hee Park","doi":"10.1038/s41523-024-00669-9","DOIUrl":"https://doi.org/10.1038/s41523-024-00669-9","url":null,"abstract":"<p>Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (<i>p</i> &lt; 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (<i>n</i> = 72) and 80.1% in the low fusion group (<i>n</i> = 125) (<i>p</i> = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; <i>p</i> = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (<i>p</i> &lt; 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (<i>p</i> = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"245 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.","authors":"Sara P Myers, Varadan Sevilimedu, Andrea V Barrio, Audree B Tadros, Anita Mamtani, Mark E Robson, Monica Morrow, Minna K Lee","doi":"10.1038/s41523-024-00674-y","DOIUrl":"10.1038/s41523-024-00674-y","url":null,"abstract":"<p><p>BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.1%] BRCA2) with clinical stage I-III breast cancer treated with NAC followed by surgery from 11/2013 to 01/2022 at Memorial Sloan Kettering Cancer Center. The majority received doxorubicin/cyclophosphamide/paclitaxel therapy (93%); BRCA1/2 carriers were more likely to receive carboplatin (p < 0.001). Overall, pCR was achieved in 42% of BRCA1 carriers, 21% of BRCA2 carriers, and 26% of noncarriers (p = 0.001). Among clinically node-positive (cN+) patients, nodal pCR was more frequent in BRCA1/2 carriers compared to noncarriers (53/96 [55%] vs. 371/856 [43%], p = 0.015). This difference was seen in HR+/HER2- (36% vs. 20% of noncarriers; p = 0.027) and TN subtypes (79% vs. 45% of noncarriers; p < 0.001). In a multivariable analysis of the overall cohort, BRCA1 status, and TN and HER2+ subtypes were independently associated with pCR. These data indicate that BRCA1 carriers may be more likely to achieve overall and nodal pCR in response to NAC compared with BRCA2 carriers and patients with sporadic disease. Further studies with a larger cohort of BRCA1/2 mutation carriers are needed, as a small sample size may have a restricted ability to detect a significant association between mutational status and pCR in sensitivity analyses stratified by subtype and adjusted for clinically relevant factors.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"63"},"PeriodicalIF":6.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cook and Move for Your Life, an eHealth intervention for women with breast cancer.","authors":"Heather Greenlee, Eileen Rillamas-Sun, Rachel L Yung, Sofia Cobos, Sidney M Donzella, Yuhan Huang, Liza Schattenkerk, Katherine Ueland, Matthew VanDoren, Samantha A Myers, Gino Garcia, Theresa King, Margarita Santiago-Torres, Chongzhi Di, Neelendu Dey, Katherine A Guthrie, Nancy E Davidson","doi":"10.1038/s41523-024-00662-2","DOIUrl":"10.1038/s41523-024-00662-2","url":null,"abstract":"<p><p>We tested the feasibility and preliminary efficacy of an online diet and physical activity program for women with early-stage breast cancer who had completed surgery, chemotherapy, and radiation therapy (ongoing endocrine therapy allowed). Participants with low fruit and vegetable (F/V) consumption and/or low moderate-to-vigorous physical activity (MVPA) levels were randomized to one of two doses - low (one Zoom group session) or high (12 Zoom group sessions) - of an online lifestyle program with the goal of improving F/V intake and MVPA. All participants received eHealth communications (text messages, study website access), a Fitbit, and a WiFi-enabled scale. Primary objectives evaluated feasibility. Secondary objectives compared the 6-month change in F/V intake and MVPA between the two dose groups. Seventy-four women (mean age = 58.4 years; 87% non-Hispanic White; mean time since diagnosis = 4.6 years) were accrued. Among women in the low dose group, 94% attended the single session; among women in the high dose group, 84% attended at least 8 of the 12 sessions. Retention at 6 months was 93%. High relative to low dose participants consumed 1.5 more servings/day of F/V at 6 months (P = 0.007) but MVPA levels did not differ between groups. We successfully implemented an online lifestyle program for early-stage breast cancer survivors. The high dose intervention demonstrated preliminary efficacy in improving F/V consumption in early-stage breast cancer survivors. Future trials can test the intervention in a larger and more diverse population of breast cancer survivors.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"62"},"PeriodicalIF":6.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International survey on invasive lobular breast cancer identifies priority research questions.","authors":"Steffi Oesterreich, Leigh Pate, Adrian V Lee, Fangyuan Chen, Rachel C Jankowitz, Rita Mukhtar, Otto Metzger, Matthew J Sikora, Christopher I Li, Christos Sotiriou, Osama S Shah, Thijs Koorman, Gary Ulaner, Jorge S Reis-Filho, Nancy M Davidson, Karen Van Baelen, Laurie Hutcheson, Siobhan Freeney, Flora Migyanka, Claire Turner, Patrick Derksen, Todd Bear, Christine Desmedt","doi":"10.1038/s41523-024-00661-3","DOIUrl":"10.1038/s41523-024-00661-3","url":null,"abstract":"<p><p>There is growing awareness of the unique etiology, biology, and clinical presentation of invasive lobular breast cancer (ILC), but additional research is needed to ensure translation of findings into management and treatment guidelines. We conducted a survey with input from breast cancer physicians, laboratory-based researchers, and patients to analyze the current understanding of ILC, and identify consensus research questions. 1774 participants from 66 countries respondents self-identified as clinicians (N = 413), researchers (N = 376), and breast cancer patients and advocates (N = 1120), with some belonging to more than one category. The majority of physicians reported being very/extremely (41%) to moderately (42%) confident in describing the differences between ILC and invasive breast cancer of no special type (NST). Knowledge of histology was seen as important (73%) and as affecting treatment decisions (51%), and most agreed that refining treatment guidelines would be valuable (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it, and would participate in an ILC clinical trials consortium. The majority of laboratory researchers, reported being and very/extremely (48%) to moderately (29%) confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets, and that ILC models are insufficient. The majority have adequate access to tissue or blood from patients with ILC. The majority of patients and advocates (52%) thought that their health care providers did not sufficiently explain the unique features of ILC. They identified improvement of ILC screening/early detection, and identification of better imaging tools as top research priorities. In contrast, both researchers and clinicians identified understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials as top research priority. In summary, we have gathered information from an international community of physicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving management and personalizing treatment for patients with ILC.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"61"},"PeriodicalIF":6.5,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression signature for predicting homologous recombination deficiency in triple-negative breast cancer.","authors":"Jia-Wern Pan, Zi-Ching Tan, Pei-Sze Ng, Muhammad Mamduh Ahmad Zabidi, Putri Nur Fatin, Jie-Ying Teo, Siti Norhidayu Hasan, Tania Islam, Li-Ying Teoh, Suniza Jamaris, Mee-Hoong See, Cheng-Har Yip, Pathmanathan Rajadurai, Lai-Meng Looi, Nur Aishah Mohd Taib, Oscar M Rueda, Carlos Caldas, Suet-Feung Chin, Joanna Lim, Soo-Hwang Teo","doi":"10.1038/s41523-024-00671-1","DOIUrl":"10.1038/s41523-024-00671-1","url":null,"abstract":"<p><p>Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"60"},"PeriodicalIF":6.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}