BCSC

BCSC
  • 文章类型: Journal Article
    乳腺癌是全世界最常见的恶性肿瘤之一。它占女性癌症引起的所有死亡病例的15%以上。乳腺癌是代表各种组织学类型的异质性疾病,分子特征,和临床资料。然而,所有的乳腺癌都组织在异质细胞群的层次结构中,一小部分癌症干细胞(乳腺癌干细胞(BCSC))在癌症进展中起着推定的作用,他们负责治疗失败。在乳腺癌的不同分子亚型中,它们呈现出不同的特点,具有特定的标记配置文件,预后,和治疗。最近的努力集中在解决Wnt,缺口,刺猬,PI3K/Akt/mTOR,和HER2信号通路。开发诊断和治疗策略能够更有效地消除肿瘤块和干细胞群。因此,关于针对“正常”乳腺癌细胞和乳腺癌干细胞亚群的适当治疗方法的知识对于成功消除癌症至关重要。
    Breast cancer is one of the most frequently detected malignancies worldwide. It is responsible for more than 15% of all death cases caused by cancer in women. Breast cancer is a heterogeneous disease representing various histological types, molecular characteristics, and clinical profiles. However, all breast cancers are organized in a hierarchy of heterogeneous cell populations, with a small proportion of cancer stem cells (breast cancer stem cells (BCSCs)) playing a putative role in cancer progression, and they are responsible for therapeutic failure. In different molecular subtypes of breast cancer, they present different characteristics, with specific marker profiles, prognoses, and treatments. Recent efforts have focused on tackling the Wnt, Notch, Hedgehog, PI3K/Akt/mTOR, and HER2 signaling pathways. Developing diagnostics and therapeutic strategies enables more efficient elimination of the tumor mass together with the stem cell population. Thus, the knowledge about appropriate therapeutic methods targeting both \"normal\" breast cancer cells and breast cancer stem cell subpopulations is crucial for success in cancer elimination.
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  • 文章类型: Journal Article
    背景:乳腺癌诊断后,目前尚不确定女性的乳腺密度知识是否会影响她们接受术前成像以检测乳房中其他癌症的意愿。我们评估了女性的乳腺密度知识及其推迟治疗的意愿,以术前测试。
    方法:我们调查了乳腺癌监测协会中年龄≥18岁的女性,在之前的6-18个月内诊断出第一次乳腺癌,在诊断前的5年内至少进行过一次乳腺密度测量。我们通过logistic回归评估了女性的乳腺密度知识和愿意推迟治疗6周或更长时间进行术前成像的相关性。
    结果:调查参与率为28.3%(969/3,430)。72%(469/647)的致密女性和11%(34/322)的非致密女性正确地知道自己的密度(p<0.001);所有女性中有69%(665/969)知道致密的乳房使在乳房X线照片上更难发现癌症;29%(285/969)愿意推迟治疗≥6周进行术前成像。延迟治疗的意愿与自我报告的密度没有差异(非密集与高密度的OR:0.99致密;95CI:0.50-1.96)。化疗治疗与延迟治疗意愿降低相关(OR:0.67;95CI:0.46-0.96)。先前延迟乳腺癌治疗超过3个月与延迟术前影像学治疗的意愿增加相关(OR:2.18;95CI:1.26-3.77)。
    结论:了解个人乳腺密度与术前影像学推迟6周或更长时间治疗的意愿无关,但一个女人的治疗经验方面是。
    结果:GOV:NCT02980848注册于2016年12月2日。
    BACKGROUND: Following a breast cancer diagnosis, it is uncertain whether women\'s breast density knowledge influences their willingness to undergo pre-operative imaging to detect additional cancer in their breasts. We evaluated women\'s breast density knowledge and their willingness to delay treatment for pre-operative testing.
    METHODS: We surveyed women identified in the Breast Cancer Surveillance Consortium aged ≥ 18 years, with first breast cancer diagnosed within the prior 6-18 months, who had at least one breast density measurement within the 5 years prior to their diagnosis. We assessed women\'s breast density knowledge and correlates of willingness to delay treatment for 6 or more weeks for pre-operative imaging via logistic regression.
    RESULTS: Survey participation was 28.3% (969/3,430). Seventy-two percent (469/647) of women with dense and 11% (34/322) with non-dense breasts correctly knew their density (p < 0.001); 69% (665/969) of all women knew dense breasts make it harder to detect cancers on a mammogram; and 29% (285/969) were willing to delay treatment ≥ 6 weeks to undergo pre-operative imaging. Willingness to delay treatment did not differ by self-reported density (OR:0.99 for non-dense vs. dense; 95%CI: 0.50-1.96). Treatment with chemotherapy was associated with less willingness to delay treatment (OR:0.67; 95%CI: 0.46-0.96). Having previously delayed breast cancer treatment more than 3 months was associated with an increased willingness to delay treatment for pre-operative imaging (OR:2.18; 95%CI: 1.26-3.77).
    CONCLUSIONS: Understanding of personal breast density was not associated with willingness to delay treatment 6 or more weeks for pre-operative imaging, but aspects of a woman\'s treatment experience were.
    RESULTS: GOV : NCT02980848 registered December 2, 2016.
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  • 文章类型: Randomized Controlled Trial
    目的:探讨超声骨刀(UBK)联合牙科电动马达(DEM)在下颌中低位埋伏牙拔除术中的临床应用。
    方法:将2022年1月至2023年5月的200例智齿患者随机分为3组:实验组A(UBK联合DEM),实验组B(UBK结合高速涡轮手机(HSTMP)),对照组(骨凿劈冠(BCSC))。操作时间,手术期间的心理状态,疼痛,肿胀,限制张口和其他并发症的第一,记录术后第二天和第三天。
    结果:实验组A(EAG)手术时间(12.95±2.12)分钟短于实验组B(EBG)(17.06±2.25)分钟及对照组(CG)(23.43±2.18)分钟,差异有统计学意义(P<0.05)。EAG的心理状况显著低于EBG和CG(P<0.05)。术后疼痛,肿胀,EAG的张口限制和并发症明显低于EBG和CG(P<0.05)。
    结论:UBK联合DEM在下颌中下段阻塞牙拔除术中有较好的效果,预后良好,安全性高,操作时间短,患者的心理状况更好,术后疼痛低,肿胀,张口限制和并发症发生率,是目前首选的提取方法。
    To investigate the clinical application of an ultrasonic bone knife (UBK) combined with a dental electric motor (DEM) in the extraction of mandibular middle and low impacted teeth.
    From January 2022 to May 2023,200 patients with wisdom teeth were randomly divided into three groups: experimental group A (UBK combined with DEM), experimental group B (UBK combined with high-speed turbine mobile phone (HSTMP)), and the control group (bone chisel split crown (BCSC)). The operation time, psychological state during operation, pain, swelling, limitation of mouth opening and other complications on the first, second and third days after operation were recorded.
    The operation time of experimental group A (EAG) (12.95 ± 2.12) minutes was shorter than that of experimental group B (EBG) (17.06 ± 2.25) minutes and the control group (CG) (23.43 ± 2.18) minutes, and the difference was statistically significant (P < 0.05). The psychological state of the EAG was significantly lower than that of the EBG and CG (P < 0.05). The postoperative pain, swelling, limitation of mouth opening and complications in the EAG were significantly lower than those in the EBG and CG (P < 0.05).
    UBK combined with DEM in the extraction of mandibular middle and low obstructed teeth has good results, good prognosis, high safety, short operation time, better psychological status of patients, low postoperative pain, swelling, mouth opening restriction and complication rate, and is currently the preferred extraction method.
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  • 文章类型: Journal Article
    乳腺癌(BC)是最常见的恶性肿瘤,也是女性癌症死亡的最大原因。肿瘤细胞与肿瘤微环境因素之间的相互作用对肿瘤的进展有重要影响。存在于乳腺癌肿瘤微环境中的关键促炎细胞因子之一是TNF-α。这项研究的目的是评估TNF-α(1周)与p38或TAK1抑制剂以及二甲双胍对诱导细胞死亡的长期作用,肿瘤干细胞与转移标志物CXCR4的表达。将MCF-7和MDA-MB-231细胞用TNF-α处理一周,然后用Takinib联合治疗,SB203580或二甲双胍;在完成所有治疗后,细胞增殖,细胞死亡,测定CXCR4、CD44和CD24的表面表达。结果表明,单独使用TNF-α或与Takinib联合治疗,与对照组相比,SB203580和二甲双胍提高了两种细胞系中细胞死亡的诱导。TNF-α也增加MCF-7细胞中CXCR4的表达,但它降低了其在MDA-MB-231细胞中的表达。此外,在单独使用TNF-α或与SB203580和二甲双胍联合治疗的MDA-MB-231细胞中,乳腺癌干细胞(BCSC)群体减少。虽然,在MCF-7细胞中,仅TNF-α和Takinib的组合以时间依赖性方式减少BCSC群体。总之,我们发现TNF-α单独或联合其他治疗可影响乳腺癌的进展。
    Breast cancer (BC) is the most common malignancy, and the largest cause of cancer death among women. The interactions between tumor cells and tumor micro environmental factors have a major impact on tumor progression. One of the critical pro-inflammatory cytokines present in breast cancer tumor microenvironment is TNF-α. The aim of this study was to evaluate the long-term effect of TNF-α (1 week) along with p38 or TAK1 inhibitors as well as metformin on induction of cellular death, cancer stem cell and expression of metastatic marker CXCR4. MCF-7 and MDA-MB-231 cells were treated with TNF-α for one week and then were treated with combination of Takinib, SB203580 or Metformin; after all treatments were done, cell proliferation, cellular death, surface expression of CXCR4, CD44 and CD24 were determined. The results showed that treatment with TNF-α alone or in combination with Takinib, SB203580 and metformin elevated induction of cellular death in both cell lines compared to the control group. TNF-α also increased CXCR4 expression in MCF-7 cells, but it reduced its expression in the MDA-MB-231 cells. Also, breast cancer stem cells (BCSCs) population decreased in MDA-MB-231 cells treated with TNF-α alone or in combination with SB203580 and metformin. Although, in MCF-7 cells only combination of TNF-α and Takinib reduced BCSCs population in a time dependent manner. Altogether, we showed that TNF-α alone or in combination with other treatments can affect the progression of breast cancer.
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  • 文章类型: Case Reports
    具有一级乳腺癌家族史的女性通常被建议在比其亲属被诊断的年龄小10岁时开始筛查。缺乏证据来确定他们应该提前多久开始。
    使用1996年至2016年乳腺癌监测联盟筛查乳房X线照片的数据,作者构建了306147名30-59岁女性的队列,其中包含乳腺癌一级家族史和诊断时相对年龄的信息。作者比较了有和没有一级乳腺癌家族史的女性的5年累积乳腺癌发病率,并根据诊断时的相对年龄和筛查年龄进行了比较。
    在纳入研究的306,147名女性中,约11%的人报告有一级乳腺癌家族史,共发现3885例乳腺癌病例.报告在40至49岁之间的相对诊断并在30至39岁或40至49岁之间进行筛查的女性乳腺癌的5年累积发病率相似(分别,18.6/1000;95%置信区间[CI],12.1,25.7;18.4/1000;95%CI,13.7,23.5)作为在50-59岁之间进行筛查的无家族史的女性(18.0/1000;95%CI,17.0,19.1)。对于35至45岁的亲属诊断年龄,在诊断年龄前5-8年开始筛查,乳腺癌的5年累积发病率为15.2/1000,平均50岁女性.
    在45岁或45岁之前被诊断为亲属的女性不妨考虑,在与他们的提供者协商后,比他们的亲属诊断年龄早5-8年开始筛查。
    Women with a first-degree family history of breast cancer are often advised to begin screening when they are 10 years younger than the age at which their relative was diagnosed. Evidence is lacking to determine how much earlier they should begin.
    Using Breast Cancer Surveillance Consortium data on screening mammograms from 1996 to 2016, the authors constructed a cohort of 306,147 women 30-59 years of age with information on first-degree family history of breast cancer and relative\'s age at diagnosis. The authors compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast by relative\'s age at diagnosis and by screening age.
    Among 306,147 women included in the study, approximately 11% reported a first-degree family history of breast cancer with 3885 breast cancer cases identified. Women reporting a relative diagnosed between 40 and 49 years and undergoing screening between ages 30 and 39 or 40 and 49 had similar 5-year cumulative incidences of breast cancer (respectively, 18.6/1000; 95% confidence interval [CI], 12.1, 25.7; 18.4/1000; 95% CI, 13.7, 23.5) as women without a family history undergoing screening between 50-59 years of age (18.0/1000; 95% CI, 17.0, 19.1). For relative\'s diagnosis age from 35 to 45 years of age, initiating screening 5-8 years before diagnosis age resulted in a 5-year cumulative incidence of breast cancer of 15.2/1000, that of an average 50-year-old woman.
    Women with a relative diagnosed at or before age 45 may wish to consider, in consultation with their provider, initiating screening 5-8 years earlier than their relative\'s diagnosis age.
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  • 文章类型: Journal Article
    乳腺癌是最常见的癌症之一。即使乳腺癌患者最初对治疗有反应,发展的耐药性可导致不良预后。肿瘤干细胞(CSC)是一组具有自我更新和多能分化特征的未分化细胞。现有证据表明,CSC是导致原发性肿瘤异质性的决定因素之一。CSCs的出现导致肿瘤复发,转移,和治疗抗性。先前的研究表明,不同的干性相关表面标志物可以识别其他乳腺癌干细胞(BCSC)亚群。解密参与诱导和维持干性的关键信号网络对于开发新的BCSC靶向策略至关重要。在这次审查中,我们回顾了BCSC的生物标志物,BCSC的关键监管机构,以及调节BCSC干性的信号网络。
    Breast cancer is one of the most common cancers. Even if breast cancer patients initially respond to treatment, developed resistance can lead to a poor prognosis. Cancer stem cells (CSCs) are a group of undifferentiated cells with self-renewal and multipotent differentiation characteristics. Existing evidence has shown that CSCs are one of the determinants that contribute to the heterogeneity of primary tumors. The emergence of CSCs causes tumor recurrence, metastasis, and therapeutic resistance. Previous studies indicated that different stemness-associated surface markers can identify other breast cancer stem cell (BCSC) subpopulations. Deciphering the critical signaling networks that are involved in the induction and maintenance of stemness is essential to develop novel BCSC-targeting strategies. In this review, we reviewed the biomarkers of BCSCs, critical regulators of BCSCs, and the signaling networks that regulate the stemness of BCSCs.
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  • 文章类型: Journal Article
    目的:我们通过近期诊断为乳腺癌的女性术前使用乳腺MRI评估了乳腺癌手术治疗决策质量和遗憾的自我报告。
    方法:我们对乳腺癌监测联盟中确定的957名年龄在18岁以上的0-III期乳腺癌女性进行了调查。参与者自我报告接受了术前乳腺MRI检查。主要结果是乳腺癌手术决策质量量表(BCS-DQI)(连续结果)和决策后悔量表(将结果分为任意/无)中的过程测量。具有线性和logit链接的广义估计方程用于估计乳腺MRI和主要结果之间的调整关联。所有分析也按乳腺密度分层。
    结果:调查参与率为27.9%(957/3430)。研究人群主要是>60岁,白色,受过大学教育,被诊断出患有早期乳腺癌.据报道,46%的女性进行了术前乳腺MRI检查。年龄较小(<50岁)的女性比例较高,商业保险,和自我检测他们的乳腺癌报告术前乳腺MRI使用。在调整后的分析中,术前使用乳腺MRI与不使用乳腺MRI相比,决策质量评分较小但具有统计学意义的较高(69.5vs64.7,p值=0.043).与未使用相比,报告术前使用乳腺MRI的女性的决策遗憾没有显着差异(54.2%对48.7%,分别,p值=0.11)。对于任一主要结局,按乳腺密度分层时,研究结果均无变化。
    结论:在乳腺癌的诊断检查中使用乳腺MRI并没有负面地改变妇女在早期存活时对手术治疗决定的看法。
    背景:NCT03029286。
    OBJECTIVE: We evaluated self-report of decision quality and regret with breast cancer surgical treatment by pre-operative breast MRI use in women recently diagnosed with breast cancer.
    METHODS: We conducted a survey with 957 women aged 18 + with stage 0-III breast cancer identified in the Breast Cancer Surveillance Consortium. Participants self-reported receipt of pre-operative breast MRI. Primary outcomes were process measures in the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) (continuous outcome) and Decision Regret Scale (dichotomized outcome as any/none). Generalized estimating equations with linear and logit link were used to estimate adjusted associations between breast MRI and primary outcomes. All analyses were also stratified by breast density.
    RESULTS: Survey participation rate was 27.9% (957/3430). Study population was primarily > 60 years, White, college educated, and diagnosed with early-stage breast cancer. Pre-operative breast MRI was reported in 46% of women. A higher proportion of women who were younger age (< 50 years), commercially insured, and self-detected their breast cancer reported pre-operative breast MRI use. In adjusted analysis, pre-operative breast MRI use compared with no use was associated with a small but statistically significantly higher decision quality scores (69.5 vs 64.7, p-value = 0.043). Decision regret did not significantly differ in women who reported pre-operative breast MRI use compared with no use (54.2% v. 48.7%, respectively, p-value = 0.11). Study results did not vary when stratified by breast density for either primary outcome.
    CONCLUSIONS: Breast MRI use in the diagnostic work-up of breast cancer does not negatively alter women\'s perceptions of surgical treatment decisions in early survivorship.
    BACKGROUND: NCT03029286.
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  • 文章类型: Journal Article
    目的:黑人乳腺癌(BC)幸存者患对侧乳腺癌(CBC)的风险高于白人。现有的CBC风险预测工具主要是基于白人女性开发的。为了解决这种种族差异,这是至关重要的是开发的工具,为黑人妇女,以帮助他们了解他们的实际风险的CBC。
    方法:我们提出了一个绝对风险预测模型,CBCRisk-Black,特别适用于BlackBC患者。它使用来自两个来源的黑人女性数据:乳腺癌监测联合会(BCSC)和监测,流行病学,和最终结果(SEER)。首先,建立了一个估计相对风险(RR)的匹配lasso逻辑回归模型。然后,它与相关的危险率和可归因风险相结合,以获得绝对风险。六折交叉验证用于内部验证CBCRisk-Black。我们还将CBCRisk-Black与CBCRisk进行了比较,现有的CBC风险预测模型。
    结果:RR模型使用来自BCSC的744名黑人女性(186例)的数据。CBCRisk-Black有四个危险因素(与基线相比的RR):乳腺密度(异质/极致密为2.13),BC家族史(2.28表示是),第一个BC肿瘤大小(T3/T4为2.14,TIS为1.56),首次诊断为BC的年龄(<40时为1.41)。对于CBCRisk-Black,3年和5年预测的接收器工作特征曲线(AUC)下的面积为0.72和0.65,而对于CBCRisk则为0.65和0.60。
    结论:CBCRisk-Black通过提供更准确和个性化的CBC风险评估,可以作为临床医生为BlackBC患者提供咨询的有用工具。
    OBJECTIVE: Black breast cancer (BC) survivors have a higher risk of developing contralateral breast cancer (CBC) than Whites. Existing CBC risk prediction tools are developed based on mostly White women. To address this racial disparity, it is crucial to develop tools tailored for Black women to help them inform about their actual risk of CBC.
    METHODS: We propose an absolute risk prediction model, CBCRisk-Black, specifically for Black BC patients. It uses data on Black women from two sources: Breast Cancer Surveillance Consortium (BCSC) and Surveillance, Epidemiology, and End Results (SEER). First, a matched lasso logistic regression model for estimating relative risks (RR) is developed. Then, it is combined with relevant hazard rates and attributable risks to obtain absolute risks. Six-fold cross-validation is used to internally validate CBCRisk-Black. We also compare CBCRisk-Black with CBCRisk, an existing CBC risk prediction model.
    RESULTS: The RR model uses data from BCSC on 744 Black women (186 cases). CBCRisk-Black has four risk factors (RR compared to baseline): breast density (2.13 for heterogeneous/extremely dense), family history of BC (2.28 for yes), first BC tumor size (2.14 for T3/T4, 1.56 for TIS), and age at first diagnosis of BC (1.41 for < 40). The area under the receiver operating characteristic curve (AUC) for 3- and 5-year predictions are 0.72 and 0.65 for CBCRisk-Black while those are 0.65 and 0.60 for CBCRisk.
    CONCLUSIONS: CBCRisk-Black may serve as a useful tool to clinicians in counseling Black BC patients by providing a more accurate and personalized CBC risk estimate.
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  • 文章类型: Journal Article
    由于乳腺癌干细胞(BCSCs)的存在,放疗后肿瘤复发是一个临床挑战,机制尚不清楚。显示低水平的ROS和增强的抗氧化剂防御有助于增加抗辐射性。然而,Nrf2-Keap1-Bach1信号在BCSC的放射抗性中的作用仍然难以捉摸。分级辐射增加了ALDH表达亚群的百分比及其球体形成能力,在BCSC中促进间充质到上皮的转化并增强放射抗性。辐射通过Keap1沉默激活Nrf2并增强BCSC的肿瘤启动能力。此外,Nrf2敲低抑制ALDH+群体和干细胞标记,通过降低克隆性降低辐射抗性,并阻断免疫受损小鼠的致瘤能力。Keap1沉默的潜在机制可能是通过miR200a,当我们观察到它的表达显著增加时,Keap1或GSK-3β的启动子甲基化没有改变。我们的数据表明ALDH+BCSC人群通过Nrf2-Keap1途径促进乳腺肿瘤的放射抗性,用miR200a靶向这个细胞群体可能是有益的,但需要详细的研究。我们的结果支持Nrf2-Keap1信号传导控制间充质-上皮可塑性的观点,调节肿瘤启动能力并促进BCSC的放射抗性。
    Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 signaling in the radioresistance of BCSCs remains elusive. Fractionated radiation increased the percentage of the ALDH-expressing subpopulation and their sphere formation ability, promoted mesenchymal-to-epithelial transition and enhanced radioresistance in BCSCs. Radiation activated Nrf2 via Keap1 silencing and enhanced the tumor-initiating capability of BCSCs. Furthermore, knockdown of Nrf2 suppressed ALDH+ population and stem cell markers, reduced radioresistance by decreasing clonogenicity and blocked the tumorigenic ability in immunocompromised mice. An underlying mechanism of Keap1 silencing could be via miR200a, as we observed a significant increase in its expression, and the promoter methylation of Keap1 or GSK-3β did not change. Our data demonstrate that ALDH+ BCSC population contributes to breast tumor radioresistance via the Nrf2-Keap1 pathway, and targeting this cell population with miR200a could be beneficial but warrants detailed studies. Our results support the notion that Nrf2-Keap1 signaling controls mesenchymal-epithelial plasticity, regulates tumor-initiating ability and promotes the radioresistance of BCSCs.
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  • 文章类型: Journal Article
    OBJECTIVE: Women with a first-degree family history of breast cancer (FHBC) are sometimes advised to initiate screening mammography when they are 10 years younger than the age at which their youngest relative was diagnosed, despite a lack of unambiguous evidence that this is an effective strategy. It is unknown how often this results in women initiating screening earlier (< 40 years) than screening guidelines recommend for average-risk women.
    METHODS: We examined screening initiation age by FHBC and age at diagnosis of the youngest relative using data collected by the Breast Cancer Surveillance Consortium on 74,838 first screening mammograms performed between 1996 and 2016.
    RESULTS: Of the 74,838 women included in the study, nearly 9% reported a FHBC. Approximately 16.8% of women who initiated mammography before 40 years reported a FHBC. More women with a FHBC than without initiated screening < 40 years (48% vs. 23%, respectively). Among women with a FHBC who initiated screening < 40 years, 65% were 10 years younger than the age at which their relative was diagnosed.
    CONCLUSIONS: Women with a first-degree relative diagnosed with breast cancer were more likely to start screening before 40 years than women reporting no FHBC, especially if their relative was diagnosed before 50 years.
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