Risk Factors for Second Primary Breast Cancer Among DCIS Survivors

摘要： 拟议的研究是对我们目前资助的项目的竞争性更新，该项目正在调查如何 流行病学因素、临床和病理特征以及肿瘤标记物的表达影响 第一例原发浸润性乳房幸存者患第二原发浸润性对侧乳腺癌的风险 癌症。在这里，我们建议通过评估与二次原发疾病风险相关的因素来扩展这项工作 导管原位癌(DCIS)幸存者中的乳腺癌。DCIS的发病率增加了7.2- 在美国，从1980年到2001年，很大程度上是由于广泛的乳腺癌筛查。DCIS 病变对可用的治疗非常敏感，与疾病相关的五年存活率接近 100%然而，DCIS幸存者患第二次乳腺癌的风险是普通人的3.4到8.6倍 与普通女性罹患首例乳腺癌的风险相比。最近的 DCIS发病率的快速上升导致了大量且不断增长的DCIS幸存者 特别容易患上第二次乳腺癌。并不是所有DCIS患者都会继续发展为 第二种乳腺癌，所以某些手术和辅助治疗DCIS的组合构成了过度- 治疗那些第二次乳腺癌风险较低的人，而其他人则构成对那些患有第二次乳腺癌的人治疗不足 风险很高。然而，目前缺乏有意义的预测指标来表明哪些DCIS幸存者 罹患第二次乳腺癌的风险高或低。这样的预言家可能是重要的指南。 帮助这些患者和他们的临床医生选择最合适的疗程和随后的治疗 随访。我们建议调查流行病学、临床和组织病理学特征 DCIS对DCIS幸存者罹患第二原发乳腺癌的风险有影响。我们将招募515名患者 确诊为DCIS和随后确诊的第二次原发原位或浸润性乳腺癌，以及对照 由1,030名仅被诊断为DCIS的患者组成的小组，以解决以下具体目标：1)如何 乳腺癌的流行病学危险因素，包括生殖特征、人体测量、 使用外源性激素、乳房X光检查密度和乳腺癌家族史会影响患乳腺癌的风险。 第二原发癌，对侧第二原发癌，同侧第二 DCIS幸存者中的原发乳腺癌？以及2)DCIS幸存者的临床和组织病理学特征 DCIS，包括治疗、肿瘤分级和组织学亚型对第二原发乳的影响风险 总体癌症，对侧第二原发癌，同侧第二原发癌 在DCIS的幸存者中？这项拟议的研究将为快速增长的 DCIS存活者的人数，因为其结果可能有助于调节他们发展第二个初级乳房的风险 并为他们关于DCIS治疗和随后的乳腺癌筛查的决策提供信息。

ABSTRACT: 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.