Wachtel Mitchell S, Yang Shengping, Dissanaike Sharmila, Margenthaler Julie A
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
PLoS One. 2015 Sep 18;10(9):e0138556. doi: 10.1371/journal.pone.0138556. eCollection 2015.
A decline in breast cancer incidence has been attributed to the reduction in hormone replacement therapy (HRT) prescriptions since the publication of the landmark WHIT paper in 2003. Concurrently, a relationship between HRT and cerebrovascular disease incidence has also been suggested. No generalized analysis of HRT prescription rates and breast cancer incidence rates that included more than seven years of data. We hypothesized that detailed analysis of SEER data would clarify the relationship between HRT use and breast cancer incidence. Given the large decline in HRT prescription rates uncovered, analyses of potential complications were also conducted, with the understanding that a small effect or one limited to a subpopulation, such as a single race, might not be detected.
Incidence rates (per 100,000 women) and standard errors for ductal and lobular breast carcinomas, and endometrioid /endometrial carcinomas in women over 50 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database 1992-2012. From the Medical Expenditure Panel Survey 1996-2012 weighted counts and standard errors of hormone replacement therapy (HRT) prescriptions for women over 50 years were obtained. Using the National Hospital Discharge Survey (NHDS), 1996-2010 weighted counts and standard errors of femoral neck fractures, total hip replacements, acute myocardial infarctions, and cerebral infarctions were obtained for 50+ year men and women. Weighted counts and standard errors were divided by US census figures and multiplied by 100,000. Joinpoint regression was used to analyze rates.
Beginning 2001, HRT prescription rates dropped dramatically, 2001-2012 AAPC -14.9 (95% CI -17.4, -12.4). Breast cancer rates, which began to decline in 1999, increased after 2003; 2012 rates were similar to those seen in 2001 for both ductal, AAPC 0.1 (-0.4, 0.6) and lobular, AAPC 0.5 (-0.4, 1.5), carcinoma. Endometrial carcinoma rates increased, 2001-2012 AAPC 3.5 (3.1, 3.8), arguing against a negative effect of HRT discontinuation of endometrial carcinoma. Tests for parallelism failed to detect APC differences among genders for femoral neck fractures (P = 0.24), for total hip replacements (P = 0.11), for myocardial infarctions (P = 0.10), or for cerebral infarctions (P = 0.19), precluding any assignment of general effect on these disorders by HRT.
Using SEER data, we demonstrated that changes in breast cancer rates cannot be explained by HRT prescription rate changes.
自2003年具有里程碑意义的WHI报告发表以来,乳腺癌发病率的下降归因于激素替代疗法(HRT)处方的减少。同时,也有人提出HRT与脑血管疾病发病率之间存在关联。此前没有对包含超过七年数据的HRT处方率和乳腺癌发病率进行综合分析。我们推测,对监测、流行病学和最终结果(SEER)数据进行详细分析将阐明HRT使用与乳腺癌发病率之间的关系。鉴于发现HRT处方率大幅下降,我们还对潜在并发症进行了分析,因为我们明白可能检测不到微小的影响或仅限于亚人群(如单一种族)的影响。
从1992 - 2012年的SEER数据库中获取50岁以上女性导管癌、小叶癌以及子宫内膜样/子宫内膜癌的发病率(每10万名女性)和标准误。从1996 - 2012年医疗支出面板调查中获取50岁以上女性激素替代疗法(HRT)处方的加权计数和标准误。利用1996 - 2010年国家医院出院调查(NHDS),获取50岁及以上男性和女性股骨颈骨折、全髋关节置换、急性心肌梗死和脑梗死的加权计数和标准误。加权计数和标准误除以美国人口普查数据,再乘以100,000。采用连接点回归分析发病率。
从2001年开始,HRT处方率急剧下降,2001 - 2012年平均年度百分比变化(AAPC)为 - 14.9(95%置信区间 - 17.4, - 12.4)。乳腺癌发病率在1999年开始下降,2003年后上升;2012年导管癌发病率(AAPC 0.1( - 0.4,0.6))和小叶癌发病率(AAPC 0.5( - 0.4,1.5))与2001年相似。子宫内膜癌发病率上升,2001 - 2012年AAPC为3.5(3.1,3.8),这表明HRT停用对子宫内膜癌没有负面影响。平行性检验未能检测到股骨颈骨折(P = 0.24)、全髋关节置换(P = 0.11)、心肌梗死(P = 0.10)或脑梗死(P = 0.19)在不同性别间的AAPC差异,排除了HRT对这些疾病有普遍影响的可能性。
利用SEER数据,我们证明乳腺癌发病率的变化无法用HRT处方率的变化来解释。