Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2022 Aug 2;31(8):1582-1592. doi: 10.1158/1055-9965.EPI-21-1471.
Identifying risk factors for aggressive forms of breast cancer is important. Tumor factors (e.g., stage) are important predictors of prognosis, but may be intermediates between prediagnosis risk factors and mortality. Typically, separate models are fit for incidence and mortality postdiagnosis. These models have not been previously integrated to identify risk factors for lethal breast cancer in cancer-free women.
We combined models for breast cancer incidence and breast cancer-specific mortality among cases into a multi-state survival model for lethal breast cancer. We derived the model from cancer-free postmenopausal Nurses' Health Study women in 1990 using baseline risk factors. A total of 4,391 invasive breast cancer cases were diagnosed from 1990 to 2014 of which 549 died because of breast cancer over the same period.
Some established risk factors (e.g., family history, estrogen plus progestin therapy) were not associated with lethal breast cancer. Controlling for age, the strongest risk factors for lethal breast cancer were weight gain since age 18: > 30 kg versus ± 5 kg, RR = 1.94 [95% confidence interval (CI) = 1.38-2.74], nulliparity versus age at first birth (AAFB) < 25, RR = 1.60 (95% CI = 1.16-2.22), and current smoking ≥ 15 cigarettes/day versus never, RR = 1.42 (95% CI = 1.07-1.89).
Some breast cancer incidence risk factors are not associated with lethal breast cancer; other risk factors for lethal breast cancer are not associated with disease incidence.
This multi-state survival model may be useful for identifying prediagnosis factors that lead to more aggressive and ultimately lethal breast cancer.
识别乳腺癌侵袭性形式的风险因素很重要。肿瘤因素（例如分期）是预后的重要预测因素，但可能是诊断前风险因素与死亡率之间的中介。通常，为诊断后发病率和死亡率分别拟合模型。这些模型以前没有整合过，以确定无癌女性致命性乳腺癌的风险因素。
我们将病例的乳腺癌发病率和乳腺癌特异性死亡率模型合并到一个致命性乳腺癌的多状态生存模型中。我们使用 1990 年基线风险因素从无癌症的绝经后护士健康研究女性中得出该模型。1990 年至 2014 年期间诊断出 4391 例浸润性乳腺癌病例，同期有 549 例死于乳腺癌。
一些已确立的风险因素（例如家族史、雌激素加孕激素治疗）与致命性乳腺癌无关。控制年龄后，致命性乳腺癌最强的风险因素是 18 岁以后的体重增加：> 30 公斤与± 5 公斤相比，RR = 1.94 [95%置信区间（CI）= 1.38-2.74]，初产年龄（AAFB）< 25 岁的未婚与初产年龄（AAFB）< 25 岁的未婚相比，RR = 1.60 [95%置信区间（CI）= 1.16-2.22]，当前吸烟≥15 支/天与从不吸烟相比，RR = 1.42 [95%置信区间（CI）= 1.07-1.89]。
一些乳腺癌发病率风险因素与致命性乳腺癌无关；其他致命性乳腺癌的风险因素与疾病发病率无关。
这种多状态生存模型可能有助于识别导致更具侵袭性并最终致命性乳腺癌的诊断前因素。
