Risk Factors for Second Primary Breast Cancer Among DCIS Survivors

描述（由申请人提供）：拟议的研究是我们目前资助的项目的竞争性更新，该项目正在调查流行病学因素，临床和病理学特征以及肿瘤标志物表达如何影响第一原发性浸润性乳腺癌幸存者中第二原发性浸润性对侧乳腺癌的风险。在这里，我们建议扩大这项工作，通过评估相关的因素，第二原发性乳腺癌的乳腺导管原位癌（DCIS）幸存者的风险。在美国，DCIS的发病率从1980年到2001年增加了7.2倍，这主要是由于广泛的乳腺癌筛查。DCIS病变对现有治疗非常敏感，5年疾病特异性生存率接近100%。然而，DCIS幸存者患第二种乳腺癌的风险是普通人群中女性患第一种乳腺癌的风险的3.4至8.6倍。最近DCIS发病率的快速上升已经转化为大量且不断增长的DCIS幸存者，他们特别容易发展为第二种乳腺癌。并非所有DCIS患者都会继续发展为第二种乳腺癌，因此DCIS的某些手术和辅助治疗组合构成了对第二种乳腺癌低风险患者的过度治疗，而其他组合则构成了对高风险患者的治疗不足。然而，目前缺乏有意义的指标来表明哪些DCIS幸存者患第二乳腺癌的风险较高或较低。这些指标可能是帮助这些患者及其临床医生选择最合适的治疗过程和后续护理的重要指南。我们建议调查DCIS的流行病学、临床和组织病理学特征如何影响DCIS幸存者中第二原发性乳腺癌的风险。我们将招募515名诊断为DCIS和经证实的后续第二原发性原位或浸润性乳腺癌的患者，以及由1，030名仅诊断为DCIS的患者组成的对照组，以解决以下具体目标：1）乳腺癌的流行病学危险因素，包括生殖特征、人体测量指标、外源性激素的使用、乳房X线摄影密度，和乳腺癌家族史，影响DCIS幸存者中总体第二原发性乳腺癌、对侧第二原发性乳腺癌和同侧第二原发性乳腺癌的风险？DCIS的临床和组织病理学特征，包括治疗、肿瘤分级和组织学亚型如何影响DCIS幸存者中总体第二原发性乳腺癌、对侧第二原发性乳腺癌和同侧第二原发性乳腺癌的风险？这项拟议的研究将为快速增长的DCIS幸存者提供重要信息，因为其结果可能有助于调节他们患第二原发性乳腺癌的风险，并为他们关于DCIS治疗和后续乳腺癌筛查的决策提供信息。 公共卫生相关性：在美国，所有诊断的乳腺癌中约有20%属于导管原位癌（DCIS）。DCIS患者的生存率非常高，但患第二种乳腺癌的风险也很高，而且关于哪些DCIS幸存者会和不会继续患第二种乳腺癌，我们知之甚少。本研究的主要目的是确定可能与第二次乳腺癌风险相关的流行病学，临床和组织病理学特征，这些特征可以帮助DCIS幸存者做出关于治疗和随访的决定。

DESCRIPTION (provided by applicant): The proposed study is a competitive renewal of our currently funded project that is investigating how epidemiological factors, clinical and pathological characteristics, and tumor marker expression influence the risk of second primary invasive contralateral breast cancer among survivors of a first primary invasive breast cancer. Here we propose to expand this work by evaluating factors that are related to risk of second primary breast cancers among ductal carcinoma in situ (DCIS) survivors. Incidence rates of DCIS have increased 7.2- fold from 1980 to 2001 in the United States, largely as a result of widespread breast cancer screening. DCIS lesions are very responsive to available therapies, and five-year disease-specific survival rates are close to 100%. However, DCIS survivors have a 3.4 to 8.6-fold higher risk of developing a second breast cancer compared to the risk that women in the general population have of developing a first breast cancer. The recent rapid rise in DCIS incidence rates has translated into a large and growing population of DCIS survivors who are particularly susceptible to developing a second breast cancer. Not all DCIS patients will go on to develop a second breast cancer, so certain surgical and adjuvant therapy combinations for DCIS constitute over- treatment for those at low risk of a second breast cancer, while others constitute under-treatment for those at high risk. At present, however, there is a lack of meaningful prognosticators to indicate which DCIS survivors are at high or low risk of developing a second breast cancer. Such prognosticators could be important guides to help these patients and their clinicians choose the most appropriate course of therapy and subsequent follow-up care. We propose to investigate how epidemiological, clinical, and histopathological characteristics of DCIS impact the risk of second primary breast cancers among DCIS survivors. We will recruit 515 patients diagnosed with DCIS and a verified subsequent second primary in situ or invasive breast cancer, and a control group consisting of 1,030 patients diagnosed only with DCIS to address the following specific aims: 1) How do epidemiological risk factors for breast cancer, including reproductive characteristics, anthropometric measures, use of exogenous hormones, mammographic density, and family history of breast cancer, influence the risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors?; and 2) How do the clinical and histopathological features of DCIS, including treatments, tumor grade, and histological subtype impact risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors? The proposed study will provide important information to the rapidly growing population of DCIS survivors as its results may help modulate their risk of developing a second primary breast cancer and inform their decision-making regarding DCIS treatments and subsequent breast cancer screening. Public Health Relevance: In the United States about 20% of all breast cancers diagnosed are of a type called ductal carcinoma in situ (DCIS). DCIS patients have a very high survival rate but also have a high risk of developing a second breast cancer, and little is known about which DCIS survivors will and will not go on to develop second breast cancers. The primary goal of this study is to identify epidemiological, clinical, and histopathological characteristics that may be associated with risk of second breast cancers that can help DCIS survivors make decisions regarding their treatment and follow-up.