Breast Cancer Research最新文献

{"title":"Social vulnerability is associated with advanced breast cancer presentation and all-cause mortality: a retrospective cohort study.","authors":"Kayla A Councell, Ann M Polcari, Rachel Nordgren, Ted A Skolarus, Andrew J Benjamin, Sarah P Shubeck","doi":"10.1186/s13058-024-01930-6","DOIUrl":"10.1186/s13058-024-01930-6","url":null,"abstract":"<p><strong>Background: </strong>Disparities in breast cancer mortality persist despite improvements in screening and therapeutic options. Understanding the impact of social determinants of health on disparate breast cancer outcomes is challenging due to heterogeneity of prior assessments. We examined the association between social vulnerability and breast cancer stage at diagnosis and mortality using a standardized measure of population risk for external stressors on health.</p><p><strong>Methods: </strong>Using institutional cancer registry data, female patients aged 18 or older diagnosed with breast cancer between 2012 and 2019 were assigned a 2018 Social Vulnerability Index (SVI) rank based upon home address census tract. We used multinomial logistic regression and Cox proportional hazards model to examine the relationships between SVI and breast cancer stage at diagnosis and all-cause mortality. Covariates included age and, when assessing mortality, cancer stage, comorbidities, body mass index, insurance type, and treatment regimen.</p><p><strong>Results: </strong>A total of 3,499 women with a median age of 59 (IQR 48-69) were included. 60% were White and 31% were Black. Median SVI was 0.36 (IQR 0.14-0.68) and median follow-up was 58 months (IQR 37.3-83.9). On adjusted analyses, each decile increase in SVI resulted in an 11% (OR 1.11, 95% CI 1.06-1.16, p < .001) and 15% (OR 1.15, 95% CI 1.09-1.21, p < .001) greater odds of presenting with Stage III or IV breast cancer, respectively, compared to DCIS. For patients who underwent surgery (N = 2916), each decile increase in SVI was associated with a 6% increase in all-cause mortality risk (HR 1.06, 95% CI 1.01-1.12, p = .01). Mortality risk was 1.5 times (HR 1.52, 95% CI 1.02-2.26, p = .04) greater for those in the most vulnerable quartile compared to the least vulnerable quartile.</p><p><strong>Conclusions: </strong>Women living in socially vulnerable communities presented with more advanced breast cancers and suffered worse survival. The SVI can be used to identify patients at risk for delayed cancer presentation and increased mortality. This tool can inform geographically targeted resource allocation and interventions aimed at reducing breast cancer care disparities.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"176"},"PeriodicalIF":7.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NF-κB associated markers of prognosis in early and metastatic triple negative breast cancer.","authors":"Payton De La Cruz, Julia McAdams, Melanie Morales Aquino, Aileen I Fernandez, Andrew Elliott, Maryam Lustberg, Christoph Schorl, Jennifer R Ribeiro, Nicole E James","doi":"10.1186/s13058-024-01925-3","DOIUrl":"10.1186/s13058-024-01925-3","url":null,"abstract":"<p><strong>Background: </strong>Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. While PD-1 based immunotherapies overall have led to improved treatment outcomes for this disease, a diverse response to frontline chemotherapy and immunotherapy still exist in TNBC, highlighting the need for more robust prognostic markers.</p><p><strong>Methods: </strong>Tumor-intrinsic immunotranscriptomics, serum cytokine profiling, and tumor burden studies were conducted in two syngeneic mouse models to assess differential effects in both the early-stage and metastatic setting. Bioinformatic analyses of both early and metastatic TNBC patient data were performed to assess if identified NF-κB-associated factors are associated with improved patient clinical outcomes.</p><p><strong>Results: </strong>NF-κB signaling driven by lymphotoxin beta expression is associated with tumor regression in TNBC mouse models. Furthermore, lymphotoxin beta expression in patient TNBC cohorts is prognostic of improved survival outcomes.</p><p><strong>Conclusions: </strong>This study highlights the potential role for NF-κB-associated factors, specifically lymphotoxin beta to be used as prognostic markers in TNBC, which could ultimately provide insight for improved targeted treatment approaches in the clinic.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"175"},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gremlin-2 is a novel tumor suppressor that negatively regulates ID1 in breast cancer.","authors":"Jiwoo Jung, Na Hui Kim, Jayeon Park, Dayeon Lim, Minji Kwon, World Gil, Suyeon Jung, Minjeong Go, Chaeeon Kim, Ye Hwang Cheong, Mee-Hyun Lee, Hee Sun Park, Yong-Bin Eom, Sin-Aye Park","doi":"10.1186/s13058-024-01935-1","DOIUrl":"10.1186/s13058-024-01935-1","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most common cancers in women and is closely associated with obesity. Gremlin-2 (GREM2), an antagonist for bone morphogenetic proteins (BMPs), has been considered an inhibitor of adipogenic differentiation in adipose-derived stromal/stem cells. However, the role of GREM2 in breast cancer cells remains largely unknown, and its signaling mechanism has yet to be clarified.</p><p><strong>Methods: </strong>Bioinformatics analysis was conducted using public databases. Breast cancer cells overexpressing mock or GREM2 were used for in vitro and in vivo studies. Cell viability, colony formation, migration, and animal studies were performed to investigate the role of GREM2 in breast cancer cells. Screening of target genes affected by GREM2 overexpression in breast cancer cells was performed through RNA sequencing (RNA-seq) analysis.</p><p><strong>Results: </strong>The expression level of GREM2 mRNA was significantly reduced in both breast cancer tissues and cell lines. Kaplan-Meier analysis showed that low expression of GREM2 and high methylation of the GREM2 promoter were each associated with poor patient survival. The low mRNA expression of GREM2 in breast cancer cells was increased by the demethylating agent decitabine. Breast cancer cells overexpressing GREM2 decreased cell proliferation when compared to control cells, both in vitro and in vivo. Through comparison of RNA-seq analysis between cell lines and tissue samples, gene ontologies that were consistently upregulated or downregulated by GREM2 in breast cancer were identified. In particular, the expression of inhibitor of DNA-binding-1 (ID1) was repressed by GREM2. BMP2 is one of the upstream regulators that increases the expression of ID1, and the expression of ID1 reduced by GREM2 was restored by overexpression of BMP2. Also, the migration ability of breast cancer cells, which had been suppressed by GREM2, was restored by BMP2 or ID1.</p><p><strong>Conclusions: </strong>Low expression of GREM2 in breast cancer cells is associated with hypermethylation of the GREM2 promoter, which may ultimately contribute to poor patient survival. GREM2 participates in regulating the expression of various genes, including ID1, and is involved in suppressing the proliferation of breast cancer cells. This suggests that GREM2 has the potential to act as a novel tumor suppressor in breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"174"},"PeriodicalIF":7.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering immune cell-associated genes in breast cancer: based on summary data-based Mendelian randomized analysis and colocalization study.","authors":"Jingyang Liu, Wen Sun, Ning Li, Haibin Li, Lijuan Wu, Huan Yi, Jianguang Ji, Deqiang Zheng","doi":"10.1186/s13058-024-01928-0","DOIUrl":"10.1186/s13058-024-01928-0","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer, which is the most prevalent form of cancer among women globally, encompasses various subtypes that demand distinct treatment approaches. The tumor microenvironment and immune response are of crucial significance in the development and progression of breast cancer. Nevertheless, there has been scant evidence concerning the genes within breast cancer - specific immune cells.</p><p><strong>Methods: </strong>We utilized summary data-based Mendelian randomization (SMR) to identify genes associated with breast cancer by utilizing expression quantitative trait loci (eQTL) datasets for 14 different immune cell types and genome-wide association studies (GWAS) for overall breast cancer and its subtypes. Furthermore, colocalization analysis was carried out to evaluate whether the observed association in SMR analyses is influenced by the same causal variant. Replication analysis and bulk RNA sequencing (bulkRNA-seq) analysis were employed to validate promising immune genes as potential drug targets.</p><p><strong>Results: </strong>After correcting for the rate of false discovery, we discovered a total of 17 genes in 9 immune cell types that were significantly associated with overall breast cancer and its subtypes. The genes KCNN4, L3MBTL3, ZBTB38, MDM4, and TNFSF10 were identified in overall breast cancer and its subtypes. Colocalization analyses provided robust evidence in support of these associations. Notably, the KCNN4 gene in non-classical MONOcytes (MONOnc) was further validated through replication analysis and bulkRNA-seq analysis.</p><p><strong>Conclusion: </strong>In summary, our research has revealed a repertoire of genes within diverse immune cells associated with breast cancer. KCNN4 gene in non-classical MONOcytes (MONOnc) exhibited a negative association with overall breast cancer and its subtypes, which was identified as a potential drug target for breast cancer, opening up new avenues for therapeutic interventions.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"172"},"PeriodicalIF":7.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Quantification of intratumoral heterogeneity using habitat-based MRI radiomics to identify HER2-positive, -low and -zero breast cancers: a multicenter study.","authors":"Haoquan Chen, Yulu Liu, Jiaqi Zhao, Xiaoxuan Jia, Fan Chai, Yuan Peng, Nan Hong, Shu Wang, Yi Wang","doi":"10.1186/s13058-024-01938-y","DOIUrl":"10.1186/s13058-024-01938-y","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"173"},"PeriodicalIF":7.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic recurrence in women diagnosed with non-metastatic breast cancer: a systematic review and meta-analysis.","authors":"Eileen Morgan, Colette O'Neill, Richa Shah, Oliver Langselius, Yaqi Su, Clara Frick, Hanna Fink, Aude Bardot, Paul M Walsh, Ryan R Woods, Lou Gonsalves, Jan F Nygård, Serban Negoita, Esmeralda Ramirez-Pena, Karen Gelmon, Nicoleta Antone, Miriam Mutebi, Sabine Siesling, Fatima Cardoso, Julie Gralow, Isabelle Soerjomataram, Melina Arnold","doi":"10.1186/s13058-024-01881-y","DOIUrl":"10.1186/s13058-024-01881-y","url":null,"abstract":"<p><strong>Background: </strong>To assess proportions of metastatic recurrence in women initially diagnosed with non-metastatic breast cancer by stage at diagnosis, breast cancer subtype, calendar period and age.</p><p><strong>Methods: </strong>A systematic search of MEDLINE and Web of Science databases (January 2010-12 May 2022) was conducted. Studies reporting the proportion of distant metastatic recurrence in women with non-metastatic breast cancer were identified and outcomes and characteristics were extracted. Risk of bias was assessed independently by two reviewers. Random-effects meta-analyses of proportions were used to calculate pooled estimates and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>193 studies covering over 280,000 patients were included in the main analysis. Pooled proportions of metastatic recurrence increased with longer median follow-up time from 12.2% (95% CI 10.5-14.0%) at 1-4 years post diagnosis, 14.3% (95% CI 12.9-15.7%) at 5-9 years to 23.3% (95% CI 20.1-26.8) at 10 years or more. Regional variation was observed with pooled estimates ranging from 11.0% (95% CI 8.5-13.7%) in Europe to 26.4% (95% CI 16.7-37.4%) in Africa (1-4 years follow-up). Proportions of recurrence were higher in studies with diagnosis before 2000 (22.2%, 95% CI 15.1-30.3) compared to studies with diagnosis from 2000 onwards (12.8%, 95% CI 11.7-14.0). At 1-4 years median follow-up, pooled proportions of metastatic recurrence were higher in women with hormone receptor negative (15.2%, 95% CI 12.0-18.7%) compared with receptor positive disease (9.6%, 95% CI 6.2-13.6%) and in women with locally advanced (33.2%, 95% CI 24.7-42.3%) relative to early disease at initial diagnosis (4.8%, 95% CI 2.5-7.8%). Proportions were higher in those under 50 years compared with 70+ years, 18.6% (95% CI 15.9-21.4%) versus 13.3% (95% CI 9.2, 18.0%), respectively. Heterogeneity was high in all meta-analyses and results should be interpreted with caution.</p><p><strong>Conclusions: </strong>Higher proportions of metastatic recurrence in patients initially diagnosed at an advanced stage and in earlier calendar period emphasises the importance of early detection and treatment advancements. As the global number of breast cancer survivors increases, research and health policy efforts should be directed towards timely diagnosis and access to effective treatments and care.</p><p><strong>Study registration: </strong>PROSPERO CRD42022314500.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"171"},"PeriodicalIF":7.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response.","authors":"Parastoo Shahrouzi, Youness Azimzade, Wioletta Brankiewicz-Kopcinska, Sugandha Bhatia, David Kunke, Derek Richard, Xavier Tekpli, Vessela N Kristensen, Pascal H G Duijf","doi":"10.1186/s13058-024-01924-4","DOIUrl":"10.1186/s13058-024-01924-4","url":null,"abstract":"<p><p>Breast cancer (BCa) is a major global health challenge. The BCa genome often carries extensive somatic copy number alterations (CNAs), including gains/amplifications and losses/deletions. These CNAs significantly affect tumor development, drug response and patient survival. However, how individual CNAs contribute is mostly elusive. We identified loss of chromosome 13q14.2 as a key CNA in BCa, occurring in up to 63% of patients, depending on the subtype, and correlating with poor survival. Through multi-omics and in vitro analyses, we uncover a paradoxical role of 13q14.2 loss, promoting both cell cycle and pro-apoptotic pathways in cancer cells, while also associating with increased NK cell and macrophage populations in the tumor microenvironment. Notably, 13q14.2 loss increases BCa susceptibility to BCL2 inhibitors, both in vitro and in patient-derived xenografts. Thus, 13q14.2 loss could serve as a biomarker for BCa prognosis and treatment, potentially improving outcomes for BCa patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"170"},"PeriodicalIF":7.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 HR + HER2- breast cancer: a retrospective analysis.","authors":"Yoonwon Kook, Young-Jin Lee, Chihhao Chu, Ji Soo Jang, Seung Ho Baek, Soong June Bae, Yoon Jin Cha, Gyungyup Gong, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn","doi":"10.1186/s13058-024-01929-z","DOIUrl":"10.1186/s13058-024-01929-z","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"164"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma prolactin and postmenopausal breast cancer risk: a pooled analysis of four prospective cohort studies.","authors":"Jacob K Kresovich, Catherine Guranich, Serena Houghton, Jing Qian, Micheal E Jones, Maegan E Boutot, Mitch Dowsett, A Heather Eliassen, Montserrat Garcia-Closas, Peter Kraft, Aaron Norman, Michael Pollak, Sabina Rinaldi, Bernard Rosner, Minouk J Schoemaker, Christopher Scott, Anthony J Swerdlow, Roger L Milne, Shelley S Tworoger, Celine M Vachon, Susan E Hankinson","doi":"10.1186/s13058-024-01922-6","DOIUrl":"10.1186/s13058-024-01922-6","url":null,"abstract":"<p><strong>Background: </strong>Prolactin, a hormone produced by the pituitary gland, regulates breast development and may contribute to breast cancer etiology. However, most epidemiologic studies of prolactin and breast cancer have been restricted to single, often small, study samples with limited exploration of effect modification.</p><p><strong>Methods: </strong>The Biomarkers in Breast Cancer Risk Prediction consortium includes 8,279 postmenopausal women sampled from four prospective cohort studies, of whom 3,441 were diagnosed with invasive breast cancer after enrollment. Prolactin concentrations were measured for all study participants on plasma samples collected when all women were postmenopausal and before any breast cancer diagnosis using ELISA assays. Pooled, unconditional logistic regression models, adjusted for confounders, estimated odd ratios (OR) for associations of prolactin and postmenopausal breast cancer risk overall and stratified by breast cancer risk factors.</p><p><strong>Results: </strong>Higher plasma prolactin concentrations were positively associated with postmenopausal breast cancer risk (> 13.2 ng/mL vs. < 7.9 ng/mL, OR: 1.20, 95% CI: 1.06, 1.36; P-trend < 0.001). Although associations did not appear to vary by time since blood draw or most breast cancer risk factors, associations were primarily observed in current users of postmenopausal hormones at blood draw (> 13.2 ng/mL vs. < 7.9 ng/mL, current users, OR: 1.58, 95% CI: 1.27, 1.96, P-trend < 0.001; non-current users, OR: 1.08, 95% CI: 0.93, 1.27, P-trend = 0.11; P-heterogeneity = 0.06).</p><p><strong>Conclusion: </strong>Prolactin may be a risk factor for postmenopausal breast cancer, particularly in the context of postmenopausal hormone use. Investigations of prolactin interactions with other hormonal factors may further inform breast cancer etiology.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"169"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case-control study.","authors":"Parisa Tehranifar, Erica J Lee Argov, Shweta Athilat, Yuyan Liao, Ying Wei, Alexandra J White, Katie M O'Brien, Dale P Sandler, Mary Beth Terry","doi":"10.1186/s13058-024-01917-3","DOIUrl":"10.1186/s13058-024-01917-3","url":null,"abstract":"<p><strong>Background: </strong>Elevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.</p><p><strong>Methods: </strong>In a nested case-control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case-control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.</p><p><strong>Results: </strong>Cases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63-3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50-4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.</p><p><strong>Conclusions: </strong>Women who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"166"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}