Breast Cancer Research and Treatment最新文献

{"title":"Is axillary web syndrome a risk factor for breast cancer-related lymphedema of the upper extremity? A systematic review and meta-analysis.","authors":"Cheryl L Brunelle, Angela Serig","doi":"10.1007/s10549-024-07518-0","DOIUrl":"10.1007/s10549-024-07518-0","url":null,"abstract":"<p><strong>Purpose: </strong>To systematically review the available literature to determine if axillary web syndrome (AWS) is a risk factor for breast cancer-related lymphedema (BCRL) of the upper extremity.</p><p><strong>Methods: </strong>The study is Prospero-registered (ID CRD42024508169) and follows PRISMA guidelines. Ovid MEDLINE, PubMED, CINAHL, Embase, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform were searched February 24, 2024. Original studies including a cohort of females > 18 years of age diagnosed with AWS after breast cancer surgery and assessing BCRL outcome were included. Scoping, mapping, systematic or qualitative reviews, dissertations without peer-review and conference abstracts were excluded. Methodological quality was assessed using the Modified Downs and Black Checklist and overall certainty in the body of evidence was assessed using Cochrane's GRADE criteria (Grading of Recommendations Assessment, Development and Evaluation).</p><p><strong>Results: </strong>Nine cohort studies representing 3218 participants were included. The median incidence of AWS and BCRL was 31.79% (IQR 8.90%) and 14.29% (IQR 19.01%), respectively, across all studies. Pooled analysis indicated an odds ratio of 1.19 (95% confidence interval 0.60,2.37), with substantial heterogeneity across studies (Chi² p < 0.0001, I² = 82%). Methodological quality of the included studies was poor to fair, and there was very low certainty evidence indicating no difference in AWS for BCRL risk. The strongest study included, found that AWS more than doubles BCRL risk in the upper extremity.</p><p><strong>Conclusion: </strong>The available evidence base cannot definitively determine whether AWS imparts risk of BCRL. AWS should be considered a potential risk factor for BCRL, until definitive conclusions from future research are available.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"471-490"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458009","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":"Patient characteristics and treatment patterns of patients with locally advanced or metastatic HER2-low breast cancer, a single site descriptive study.","authors":"Connor Willis, Chia Jie Tan, Anindit Chhibber, Alexandre H Watanabe, Clara Lam, Sandhya Mehta, Jackie Kwong, Leah Park, Melissa Pavilack-Kirker, Xiaoqing Xu, Kristen Kelley, David Stenehjem","doi":"10.1007/s10549-024-07458-9","DOIUrl":"10.1007/s10549-024-07458-9","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the prevalence and characteristics of different HER2 categories among patients with advanced breast cancer (aBC) and describe treatment patterns and outcomes of those with HER2-low disease.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted via chart review at the Huntsman Cancer Institute, including patients diagnosed with aBC (stages IIIB, IIIC and IV) between 2010 and 2019. All patients with IHC1+ were considered HER2-low unless FISH was positive. Patients with IHC2+ were only classified as HER2-low if a negative FISH was documented. The prevalence and characteristics of each HER2 category were reported. Treatment patterns and survival outcomes of HER2-low patients who received first line treatment in 2017 or later were presented.</p><p><strong>Results: </strong>A total of 240 of 414 patients (58%) with aBC were HER2-low, with the majority of patients (83%) classified as hormone receptor (HR)-positive. In first line, most HR-positive patients received endocrine therapy with chemotherapy for stage IIIB/IIIC (47%) and with CDK4/6 inhibitors for stage IV breast cancer (50%) Most HR-negative patients received chemotherapy alone (92% for stage IIIB/IIIC, 60% for stage IV). In second line, chemotherapy alone was the most common modality (21.4% for HR-positive; 45.5% for HR-negative). Median overall survival was 37.7 months while median progression-free survival from first line was 18.0 months, decreasing to 8.0 months in second line.</p><p><strong>Conclusion: </strong>A substantial proportion of patients previously classified as HER2-negative have low but detectable HER2 expression and may benefit from novel HER2-directed agents, which have demonstrated clinical benefit in this population post-chemotherapy.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"619-630"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016386","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":"Phenotypes of carriers of two mutated alleles in major cancer susceptibility genes.","authors":"Yael Laitman, Anni Niskakoski, Rinal Bernstein-Molho, Lotta Koskinen, Daniel Rabina, Juha Koskenvuo, Eitan Friedman","doi":"10.1007/s10549-024-07454-z","DOIUrl":"10.1007/s10549-024-07454-z","url":null,"abstract":"<p><strong>Purpose: </strong>While cancer phenotypes in carriers of a single mutant allele in most major cancer susceptibility genes are well-established, there is a paucity of data on the phenotype of carriers of two pathogenic variants-double heterozygotes (DH) or homozygous carriers. Here, we describe the phenotype of carriers of homozygous and DH pathogenic sequence variants (PSVs) in major cancer susceptibility genes.</p><p><strong>Methods: </strong>Individuals referred for multigene panel testing at Blueprint Genetics laboratory were included. Ethically approved comparison of cancer type and age at diagnosis between DH, homozygous, and single PSV carriers was performed per gene.</p><p><strong>Results: </strong>Of 6,685 eligible participants, 928 (13.9%) were single heterozygous PSV carriers, 6 (0.09%) were homozygous PSV carriers, and 17 (0.25%) were DH PSV carriers. Mean age at diagnosis of any cancer among single PSV age was 46.8 ± 14.9 years and among DH PSV carriers 37.6 ± 13.0 years (P < 0.0001). Notably, age at diagnosis for breast cancer among single BRCA1 PSV carriers (n = 59) was 43.8 ± 8.7 years (p = 0.7606), among single BRCA2 PSV carriers (n = 52)-47.9 ± 13.0 years (p = 0.2274) compared with 42.3 ± 13.0 years among DH PSV carriers (n = 10- 9 of whom were carriers of either BRCA1 or BRCA2).</p><p><strong>Conclusion: </strong>DH for PSV in two cancer susceptibility genes is a rare event, and the mean age at cancer diagnosis is younger in DH PSV carriers compared with single PSV carriers.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"589-595"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888443","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":"Oral minoxidil for late alopecia in cancer survivors.","authors":"Alyce Mei-Shiuan Kuo, Rachel E Reingold, Kwami F Ketosugbo, Alexander Pan, Lukas Kraehenbuehl, Stephen Dusza, Devika Gajria, Diana E Lake, Jacqueline F Bromberg, Tiffany A Traina, Monica N Fornier, Ayca Gucalp, Brian M D'Alessandro, Veronica Rotemberg, Megan Dauscher, Jerry Shapiro, Shari B Goldfarb, Alina Markova, Mario E Lacouture","doi":"10.1007/s10549-024-07440-5","DOIUrl":"10.1007/s10549-024-07440-5","url":null,"abstract":"<p><strong>Purpose: </strong>Late alopecia, defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or > 6 months from initiation of endocrine therapy, negatively impacts quality of life and may affect dose intensity of adjuvant therapy. This study investigates the effect of oral minoxidil in women with chemotherapy and/or endocrine therapy-induced late alopecia.</p><p><strong>Methods: </strong>The rate of clinical response was assessed by standardized photography and quantitated with trichoscopy.</p><p><strong>Results: </strong>Two hundred and sixteen patients (mean age 57.8 ± 13.7) were included. The most common cancer diagnosis was breast, in 170 patients (79.1%). Alopecia developed after chemotherapy in 31 (14.4%) patients, endocrine monotherapy in 65 (30.1%) patients, and chemotherapy followed by endocrine therapy in 120 (55.6%) patients. In 119 patients, standardized photography assessments were used to determine clinical change in alopecia after a median of 105 (IQR = 70) days on oral minoxidil and revealed improvement in 88 (74%) patients. Forty-two patients received quantitative trichoscopic assessments at baseline and at follow-up after a median of 91 (IQR = 126) days on oral minoxidil. Patients had clinically and statistically significant increases in frontal hair shaft density (from 124.2 hairs/cm² at initial to 153.2 hairs/cm² at follow-up assessment, p = 0.008) and occipital shaft density (from 100.3 hairs/cm² at initial to 123.5 hairs/cm² at follow-up assessment. p = 0.004). No patients discontinued oral minoxidil due to adverse events.</p><p><strong>Conclusions: </strong>Overall, oral minoxidil was well tolerated by patients and may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy by increasing hair shaft and follicle density.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"491-499"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888442","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":"Letter to the editor: \"Frequency of zoledronate administration in early breast cancer\".","authors":"Wei-Zhen Tang, Wen-Xing Deng, Tai-Hang Liu","doi":"10.1007/s10549-024-07490-9","DOIUrl":"10.1007/s10549-024-07490-9","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"689-690"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124819","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":"Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors.","authors":"Sima Fansa, Wissam Ghusn, Elif Tama, Bryan Nicolalde, Diego Anazco, Stacy D ' Andre, Stephanie S Faubion, Chrisandra L Shufelt, Andres Acosta, Maria D Hurtado Andrade","doi":"10.1007/s10549-024-07450-3","DOIUrl":"10.1007/s10549-024-07450-3","url":null,"abstract":"<p><strong>Purpose: </strong>Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment.</p><p><strong>Methods: </strong>This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%).</p><p><strong>Results: </strong>We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m²) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m²). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol.</p><p><strong>Conclusions: </strong>The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"553-563"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854799","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":"Alterations in the expression of homologous recombination repair (HRR) genes in breast cancer tissues considering germline BRCA1/2 mutation status.","authors":"Izabela Laczmanska, Rafal Matkowski, Stanislaw Supplitt, Pawel Karpinski, Mariola Abrahamowska, Lukasz Laczmanski, Adam Maciejczyk, Ewelina Czykalko, Ewelina Iwaneczko, Piotr Kasprzak, Bartłomiej Szynglarewicz, Maria Sasiadek","doi":"10.1007/s10549-024-07441-4","DOIUrl":"10.1007/s10549-024-07441-4","url":null,"abstract":"<p><strong>Introduction: </strong>Homologous recombination (HR) is a crucial DNA-repair mechanism, and its disruption can lead to the accumulation of mutations that initiate and promote cancer formation. The key HR genes, BRCA1 and BRCA2, are particularly significant as their germline pathogenic variants are associated with a hereditary predisposition to breast and/or ovarian cancer.</p><p><strong>Materials and methods: </strong>The study was performed on 45 FFPE breast cancer tissues obtained from 24 and 21 patients, with and without the germline BRCA1/2 mutation, respectively. The expression of 11 genes: BRCA1, BRCA2, ATM, BARD1, FANCA, FANCB, FANCI, RAD50, RAD51D, BRIP1, and CHEK2 was assessed using Custom RT2 PCR Array (Qiagen), and results were analysed using R.</p><p><strong>Results: </strong>Cancer tissues from patients with BRCA1 or BRCA2 germline mutations displayed no significant differences in the expression of the selected HR genes compared to BRCA1 or BRCA2 wild-type cancer tissues. In BRCA1^mut cancer tissues, BRCA1 expression was significantly higher than in BRCA2^mut and BRCA wild-type cancer tissues.</p><p><strong>Conclusions: </strong>In cancer tissues harbouring either BRCA1 or BRCA2 germline mutations, no significant differences in expression were observed at the mRNA level of any tested HR genes, except BRCA1. However, the significant differences observed in BRCA1 expression between germline BRCA1^mut, germline BRCA2^mut and BRCA1/2^wt tissues may indicate a compensatory mechanism at the mRNA level to mitigate the loss of BRCA1 function in the cells.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"501-510"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854798","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":"Variation in surgical treatment by body mass index in patients with invasive lobular carcinoma of the breast.","authors":"Israel O Falade, Kayla M Switalla, Molly E Baxter, Astrid Quirarte, Helena Record, Harriet T Rothschild, Elle N Clelland, Rita A Mukhtar","doi":"10.1007/s10549-024-07452-1","DOIUrl":"10.1007/s10549-024-07452-1","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with invasive lobular carcinoma (ILC) face high rates of positive margins and completion mastectomy, which can be improved with the use of specific techniques, such as oncoplastic surgery. However, prior studies have shown that type of breast cancer surgery performed is also associated with patient factors such as elevated body mass index (BMI). Thus, this study investigates whether BMI impacts the type of surgical interventions in patients with ILC.</p><p><strong>Methods: </strong>A retrospective analysis of 705 patients with stage I-III ILC from an institutional database was conducted. Patients were stratified by BMI (underweight, normal weight, overweight, obese). Pearson's Chi-square, ANOVA, and multivariable logistic regression were used to evaluate the relationship between BMI and surgical procedures.</p><p><strong>Results: </strong>Breast-conserving surgery (BCS) was the initial operation in 60% of patients, with no significant difference by BMI. Among those undergoing BCS, patients with obese BMI were significantly more likely to undergo oncoplastic surgery (46.9% vs. 7.7%, 37.3%, and 33.6% for underweight, normal, and overweight, respectively, p = 0.032). Obese BMI patients undergoing mastectomy were less likely to have reconstruction compared to those with underweight, normal weight, and overweight BMI (44.2% vs. 50%, 71.1%, and 64.1%, p = 0.002).</p><p><strong>Conclusion: </strong>Overweight/obese BMI patients with ILC underwent different surgical interventions compared to those with lower BMI. While initial BCS rates were similar, overweight/obese patients had higher oncoplastic surgery rates in BCS and lower reconstruction rates in mastectomy. Further research is needed to understand BMI's impact on surgical decisions and outcomes in ILC.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"569-575"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911691","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":"Effect of minocycline on changes in affective behaviors, cognitive function, and inflammation in breast cancer survivors undergoing chemotherapy: a pilot randomized controlled trial.","authors":"Zihan Melink, Maryam B Lustberg, Patrick M Schnell, Jessica Mezzanotte-Sharpe, Tonya S Orchard","doi":"10.1007/s10549-024-07457-w","DOIUrl":"10.1007/s10549-024-07457-w","url":null,"abstract":"<p><strong>Purpose: </strong>Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy.</p><p><strong>Methods: </strong>This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.</p><p><strong>Results: </strong>Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).</p><p><strong>Conclusion: </strong>Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"605-617"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981712","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":"Rare germline variants in cancer-relevant genes are associated with breast cancer risk in young women with high-risk family history.","authors":"Mariya Rozenblit, Tao Qing, Yixuan Ye, Hongyu Zhao, Erin Hofstatter, Vinit Singh, Emily Reisenbichler, Michael Murray, Lajos Pusztai","doi":"10.1007/s10549-024-07560-y","DOIUrl":"https://doi.org/10.1007/s10549-024-07560-y","url":null,"abstract":"<p><strong>Introduction: </strong>It is incompletely understood why some women develop breast cancer 15-20 years earlier than the majority of women. We hypothesize that women with early-onset breast cancer and high-risk family history without germline pathogenic variants in cancer-predisposing genes (CPGs, n = 83) have a higher load of germline high functional impact variants (gHFI) in cancer hallmark genes (n = 1508) compared to healthy controls.</p><p><strong>Methods: </strong>Germline whole exome sequencing data were analyzed from 5818 breast cancer cases from UKBiobank and from 94 young women with breast cancer without CPG pathogenic variants from the Yale Cancer Prevention Clinic, and compared to 149 controls from Yale GENERATIONS project and 56,917 controls from UKBiobank. Rare gHFI variants were compared between cases and controls using the burden test and the optimal unified SNP-set Kernel Association Test (SKAT-O). We assessed germline versus somatic origins of pathway level alterations in the TCGA and Yale data.</p><p><strong>Results: </strong>In UKBiobank, higher gHFI variant load was seen in CPGs in cancer cases regardless of family history (p < 8.78 × 10^-8), and in hallmark genes in cases with family history vs controls (p = 0.0093). Similarly, numerically higher rare gHFI burden was seen in hallmark genes in the Yale cohort vs controls, but this difference was not statistically significant. Pathway level alterations were dominated by somatic events. These results suggest that rare germline variants in cancer biology-related genes partly mediate the contribution of family history to cancer risk in individuals without germline alterations in high penetrance CPGs.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726110","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}