Risk Factors for Second Primary Breast Cancer Among DCIS Survivors

摘要： 拟议的研究是我们目前资助的项目的竞争性更新，该项目正在调查如何 流行病学因素、临床和病理学特征以及肿瘤标志物表达影响了 第一次原发性浸润性乳腺癌幸存者中第二次原发性浸润性对侧乳腺癌的风险 癌在这里，我们建议通过评估与第二小学风险相关的因素来扩展这项工作 乳腺导管原位癌（DCIS）幸存者中的乳腺癌。DCIS的发病率增加了7.2- 从1980年到2001年，美国的乳腺癌发病率增加了一倍，这主要是由于广泛的乳腺癌筛查。DCIS 病变对可用的治疗非常敏感，5年疾病特异性生存率接近 百分百确定然而，DCIS幸存者发生第二次乳腺癌的风险高出3.4至8.6倍 与一般人群中女性患第一次乳腺癌的风险相比。近期 DCIS发病率的快速上升转化为大量且不断增长的DCIS幸存者， 特别容易患上第二种乳腺癌。并不是所有的DCIS患者都会发展成 第二乳腺癌，所以某些手术和辅助治疗组合DCIS构成过度- 治疗那些在低风险的第二个乳腺癌，而其他构成治疗不足的那些在 高风险。然而，目前缺乏有意义的指标来表明哪些DCIS幸存者 患第二种乳腺癌的风险很高或很低。这些指示器可能是重要的指南 帮助这些患者和他们的临床医生选择最合适的治疗过程， 后续护理。我们建议调查如何流行病学，临床和组织病理学特征， DCIS影响DCIS幸存者中第二原发性乳腺癌的风险。我们将招募515名患者 诊断为DCIS和经证实的随后的第二原发性原位或浸润性乳腺癌，以及对照组 由1，030名仅诊断为DCIS的患者组成的小组，以解决以下具体目标：1）如何 乳腺癌的流行病学风险因素，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， 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 DCIS幸存者中的原发性乳腺癌？2）临床和组织病理学特征如何影响 DCIS，包括治疗、肿瘤分级和组织学亚型影响第二原发乳腺癌的风险 总体癌症、对侧第二原发性乳腺癌和同侧第二原发性乳腺癌 在DCIS幸存者中这项研究将为迅速增长的 DCIS幸存者的人群，因为其结果可能有助于调节他们发展第二原发乳房的风险 乳腺癌的治疗，并告知他们有关DCIS治疗和随后的乳腺癌筛查的决策。

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.