Biomarkers and Breast Cancer Risk Prediction in Younger Women

年轻女性的生物标志物和乳腺癌风险预测

• 批准号: 8731842
• 负责人: Mengling Liu
• 金额: $ 62.31万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-09 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731842
• 关键词: Abbreviations; Adverse effects; Advisory Committees; Age; Age at First Live Birth; Age at Menarche; Age-Years; Aging; Area Under Curve; Biological Markers; Biopsy; Body mass index; Breast; Breast Cancer Detection; Breast Cancer Prevention; Breast Cancer Risk Assessment Tool; Calibration; Cancer and Nutrition; Characteristics; Chemoprevention; Chemopreventive Agent; Cohort Studies; Confidence Intervals; Discrimination; Estrogen Receptor Status; Estrogen Receptors; European; Family; First Degree Relative; Generations; Goals; Guernsey; Guidelines; Hormone replacement therapy; Hormones; Incidence; Individual; Inherited; International; Investigation; Mammary gland; Mammographic Density; Measurement; Measures; Menopause; Menstrual cycle; Methods; Modeling; Nested Case-Control Study; New York; Nurses' Health Study; Odds Ratio; Oral Contraceptives; Ovarian Follicle; Performance; Plasma; Population; Postmenopause; Premenopause; Prevention; Preventive; Progesterone Receptors; Prospective Studies; Receiver Operating Characteristics; Recording of previous events; Resources; Risk; SHBG gene; Serum; Services; Sex Hormone-Binding Globulin; Single Nucleotide Polymorphism; Subgroup; Sweden; Tamoxifen; Testosterone; Time; United States; Universities; Variant; Woman; Women' s Health; base; cancer risk; cohort; cost effective; improved; malignant breast neoplasm; mullerian-inhibiting hormone; older women; prospective; public health relevance; reproductive; screening; substance M; tumor; young woman

DESCRIPTION (provided by applicant): Background: The goal of this proposal is to improve the performance of the Gail breast cancer risk prediction model 2 for women 35-49 years of age, by the addition of biomarkers (testosterone or free testosterone, and/or Mullerian Inhibiting Substance (MIS)). MIS, which is detectable only in premenopausal women, was associated with a large increase in risk of both pre- and post-menopausal breast cancer in the only prospective study to date (OR = 9.8, 95% CI = 3.3 to 28.9 for the highest vs. lowest quartile). Premenopausal levels of testosterone and free testosterone have also been consistently shown to be positively associated with increased risk of both pre- and post-menopausal breast cancer. All three biomarkers vary little during the menstrual cycle, can be measured relatively inexpensively, and have good temporal reliability, i.e. a single measurement is reasonably representative of a woman's long-term average level, making them good candidates for inclusion in a risk prediction model. Aims: 1) To evaluate the association of premenopausal levels of MIS with breast cancer risk; 2) To assess whether adding biomarkers (testosterone or free testosterone, and/or MIS) to the factors included in the Gail model 2 improves the prediction performance of the model for women 35-49 years of age. Methods: The study will use the resources of eight prospective cohorts which collected serum or plasma from healthy young women and followed them up for incidence of breast cancer (Breakthrough Generations Study; CLUE II; Columbia, MO Serum Bank; Guernsey Cohort; Nurses' Health Study II; New York University Women's Health Study; Northern Sweden Mammary Screening Study; ORDET). For aim 1, a 1:2 nested case:control study (2500 cases) will be conducted. For aim 2, the performance of risk prediction models including one or two biomarkers, in addition to factors included in the Gail model 2 (age, age at menarche, age at first live birth, number of previous breast biopsies and number of first degree relatives with a history of breast cancer), will be compared to the Gail model 2 with respect to calibration and discriminatory accuracy. Impact: An improved risk prediction model will help women make more informed decisions regarding breast cancer screening and chemoprevention. This is particularly relevant to younger women for whom guidelines on screening are inconsistent. Further, tamoxifen, which is approved in the US for prevention of breast cancer in women age 35 and older who are at increased risk of breast cancer, is most likely to benefit younger women because they are at lower risk than older women of the adverse effects of tamoxifen.

描述（由申请人提供）：背景：该提案的目的是通过添加生物标志物（睾丸激素或免费睾丸激素和/或Mullerian抑制物质（MIS））来改善女性35-49岁的盖尔乳腺癌风险预测2模型2的表现。 MIS仅在绝经前妇女中才能检测到，与迄今为止唯一的前瞻性研究中，乳腺癌前和绝经后乳腺癌的风险大大增加有关（OR = 9.8，95％CI = 3.3至28.9，对于最高的四分位四分之一）。绝经前睾丸激素和游离睾丸激素水平也始终被证明与乳腺癌前和绝经后乳腺癌的风险呈正相关。在月经周期期间，所有三种生物标志物的变化都很小，可以相对廉价地测量，并且具有良好的时间可靠性，即单一测量值合理地代表了女性的长期平均水平，使其成为风险预测模型中的良好候选者。目的：1）评估绝经前MIS与乳腺癌风险的关联； 2）评估添加生物标志物（睾丸激素或游离睾丸激素和/或MIS）是否在Gail Model 2中包含的因素中是否可以改善35-49岁女性模型的预测性能。方法：该研究将使用八个前瞻性队列的资源，这些资源从健康的年轻女性那里收集血清或血浆，并跟随她们进行乳腺癌的发生率（Breakthrough Generations研究；哥伦比亚II； MO SERUM BARK； GUERNSEY COHORT； GUERNSEY COHORT； GUERNSEY COHORT; GUERNSEY COHORT;护士健康研究II; New York University妇女健康研究； Northern Sweden Sweden Mammarmary sweden Mammamary secutnening; Ordet; Ordet; Ordet; Ordet; Ordet; Ordet; Ordet）。对于AIM 1，将进行1：2的嵌套案例：将进行控制研究（2500例）。对于AIM 2，除了盖尔2中包括的因素（年龄，初潮时代，初生年龄，先前的乳房活检的数量和具有乳腺癌史的一级亲戚的数量）外，风险预测模型的性能包括一两个生物标志物，除了与校准和校准准确性相比，还将与乳腺癌的一级亲戚数量相比。影响：改进的风险预测模型将有助于女性就乳腺癌筛查和化学预防做出更明智的决定。这与年轻妇女特别相关，筛查指南不一致。此外，在美国在35岁及以上患有乳腺癌风险增加的女性批准的他莫昔芬最有可能使年轻女性受益，因为它们的风险低于他的风险，因为它们的风险低于他莫昔芬的不良反应的老年妇女。