Breast Cancer After The Women?s Health Initiative Study: Declining Incidence?

描述（由申请人提供）：本研究是根据PAR-06-294提交的，旨在调查2002年中期妇女健康倡议（WHI）结果发表后，激素治疗（HT）使用急剧下降后，乳腺癌发病率是否下降。WHI发现，与预期相反，HT并没有降低，事实上可能增加了心血管疾病的风险，同时也证实了长期使用联合雌激素加孕酮HT与乳腺癌和卵巢癌的风险增加有关。提示性证据（尽管仅基于2项研究）表明，美国乳腺癌发病率在2002年中期至2003年期间下降了7-11%，尤其是在雌激素受体阳性（ER+）肿瘤的老年妇女中。如果停止HT确实降低了乳腺癌的风险，那么2002年后美国乳腺癌发病率的最大下降应该在（a）最有可能使用HT的女性（即，白色富裕妇女，可获得医疗保健），和（B）与HT使用最密切相关的乳腺癌类型（雌激素受体阳性（ER+），小叶组织学类型，诊断时年龄>= 50岁）。为了验证这些假设，我们试图将2003-2005年的乳腺癌数据添加到我们先前为“乳腺癌发病率的社会经济趋势”研究生成的现有地理编码数据集中。本研究包括来自两个美国癌症登记处的所有原发性浸润性乳腺癌病例的数据：（1）北方加州癌症中心（NCCC，1973-2002）的原始5县集水区，和（2）马萨诸塞州癌症登记处（MCR）（1988-2002）。以1995-2005年为重点（n ~ 53，335例），我们将对2003-2005年的新数据进行地理编码到人口普查区（CT）水平，将它们与2000年CT水平的基于地区的社会经济数据联系起来，并检验3组相关假设：（1）乳腺癌发病率的首次显著下降发生在2002年中期之后;（2）自2002年中期以来，与（a）生活在不太富裕的CT中的白色非西班牙裔妇女和（B）生活在富裕和不太富裕的CT中的有色人种妇女相比，生活在更富裕的CT中的白色非西班牙裔妇女的乳腺癌发病率下降最多;（3）2002年后乳腺癌发病率下降最多的是：（a）ER+与ER-肿瘤的比较;（B）小叶和导管-小叶肿瘤与所有其他组织学类型的比较;（c）50岁及以上女性与50岁以下女性的比较。结果可能会提高乳腺癌的流行病学病因学的理解和方法，其发病率可以降低。迄今为止，只有2项研究调查了美国乳腺癌发病率是否在2002年中期妇女健康倡议结果发表后激素治疗（HT）使用急剧下降后下降，该研究发现，与预期相反，HT使用没有减少，事实上可能增加了心血管疾病的风险，同时也证实了HT的使用与乳腺癌和卵巢癌的风险增加有关。我们建议在这两项研究的基础上，使用1995-2005年美国两个基于人群的癌症登记处的数据，检查乳腺癌发病率自2002年中期以来是否有所下降，无论是总体还是特别是在：（1）最有可能使用HT的女性（即，白色富裕妇女，可获得医疗保健），和（2）与HT使用最密切相关的乳腺癌类型（雌激素受体阳性（ER+），小叶组织学类型，诊断年龄>= 50岁）。所获得的知识将导致对乳腺癌的原因和降低其发病率的方法的新见解。

DESCRIPTION (provided by applicant): This study, submitted in response to PAR-06-294, proposes to investigate whether breast cancer incidence decreased, following dramatic declines in hormone therapy (HT) use after publication of the Women's Health Initiative (WHI) results in mid-2002. The WHI found, contrary to expectations, that HT did not reduce, and may in fact have elevated, risk of cardiovascular disease, while also confirming that long-term use of the combined estrogen plus progestin HT was associated with increased risk of breast and ovarian cancer. Suggestive evidence, albeit based on only 2 studies, indicates US breast cancer incidence declined by 7-11% between mid-2002 and 2003, especially among older women with estrogen-receptor positive (ER+) tumors. If cessation of HT does reduce risk of breast cancer, it follows that the greatest post-2002 US declines in breast cancer incidence should be most evident among (a) women most likely to use HT (i.e., white affluent women with access to health care), and (b) types of breast cancer most strongly linked to HT use (estrogen receptor positive (ER+), lobular histologic type, and age at diagnosis >= 50 years old). To test these hypotheses, we seek to add breast cancer data for 2003-2005 to an existing geocoded data set we previously generated for our study on "Socioeconomic Trends in Breast Cancer Incidence." This study includes data on all incident cases of primary invasive breast from two US cancer registries: (1) the original 5- county catchment area of Northern California Cancer Center (NCCC, 1973-2002), and (2) the Massachusetts Cancer Registry (MCR) (1988-2002). Focusing on years 1995-2005 (n ~ 53,335 cases), we will geocode the new 2003-2005 data to census tract (CT) level, link them to 2000 CT-level area-based socioeconomic data, and test 3 related sets of hypotheses: (1) the first significant decline in breast cancer incidence occurred after mid-2002; (2) since mid-2002, breast cancer incidence rates have dropped most among white non-Hispanic women living in more affluent CTs, compared to (a) white non-Hispanic women living in less affluent CTs, and (b) women of color living in both more and less affluent CTs; and (3) post-2002 declines in breast cancer incidence were greatest among: (a) ER+ compared to ER- tumors; (b) lobular and ductal-lobular tumors compared to all other histologic types; and (c) women age 50 and older compared to women under age 50. Results are likely to enhance etiologic understanding of the epidemiology of breast cancer and ways its incidence can be reduced. To date, only 2 studies have examined whether US breast cancer incidence decreased following the dramatic declines in hormone therapy (HT) use after publication of the Women's Health Initiative results in mid-2002, which found, contrary to expectation, that HT use did not decrease, and may in fact have elevated, risk of cardiovascular disease, while also confirming HT use was associated with increased risk of both breast and ovarian cancer. We propose to build on these 2 studies by using data from two US population-based cancer registries for the years 1995-2005 to examine whether breast cancer incidence has declined since mid-2002, both overall and especially among: (1) women most likely to use HT (i.e., white affluent women with access to health care), and (2) types of breast cancer most strongly linked to HT use (estrogen receptor positive (ER+), lobular histologic type, and age at diagnosis >= 50 years old). The knowledge gained will lead to new insights about the causes of breast cancer and ways its incidence can be reduced.