Division of Community Health, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi, 981-1293, Japan.
Breast Cancer. 2019 Nov;26(6):687-702. doi: 10.1007/s12282-019-00972-5. Epub 2019 Apr 15.
Reproductive factors may influence breast cancer progression and patient survival; however, evidence has been limited.
The associations of reproductive factors with tumor characteristics and patient survival were analyzed among 1468 breast cancer patients diagnosed during 1997-2013 at a single institute in Japan. The patients were followed until 2016. During a median follow-up period of 8.6 years, 272 all-cause and 199 breast cancer deaths were documented.
In case-case comparisons, later age at menarche was inversely associated with advanced tumors. Nulliparous patients tended to have receptor-positive [estrogen receptor (ER)+ or progesterone receptor (PR)+] tumors. Conversely, the Cox proportional-hazards model including adjustment for tumor characteristics revealed U-shaped relationship between parity number and the risk of all-cause death among the patients overall [hazard ratio (HR) = 2.10 for nulliparous, 1.28 for 2, and 1.50 for ≥ 3 vs. one child]. According to hormone receptor, later age at menarche and later age at last birth were positively associated with the risk of all-cause death among patients with ER- and PR- cancer (menarche, HR = 2.18 for ≥ 15 vs. ≤ 12 years, p = 0.03; last birth, HR = 3.10 for ≥ 35 vs. ≤ 29 years, p = 0.01). A shorter time since last birth was associated with the risk of death among receptor-positive patients (HR = 5.72 for ≤ 4 vs. ≥ 10 years, p = 0.004).
The results indicate that the timing of menarche and parity have significant effects on patient survival, providing clues for understanding the association between women's life course and breast cancer outcome.
生殖因素可能影响乳腺癌的进展和患者的生存,但证据有限。
本研究在日本的一家机构中分析了 1997 年至 2013 年期间诊断的 1468 例乳腺癌患者的生殖因素与肿瘤特征和患者生存的关系。这些患者的随访时间截止到 2016 年。在中位随访时间为 8.6 年期间,记录了 272 例全因死亡和 199 例乳腺癌死亡。
在病例对照研究中,初潮年龄较晚与肿瘤进展呈负相关。未育患者的肿瘤往往为受体阳性(雌激素受体 [ER]+或孕激素受体 [PR]+)。相反,在包括肿瘤特征调整的 Cox 比例风险模型中,总体患者的产次与全因死亡风险呈 U 型关系[危险比(HR)=未育者 2.10、2 次 1.28、≥3 次 1.50,与 1 次生育者相比]。根据激素受体,初潮年龄较晚和末次生育年龄较晚与 ER-和 PR-乳腺癌患者的全因死亡风险呈正相关(初潮,HR=≥15 岁比≤12 岁,p=0.03;末次生育,HR=≥35 岁比≤29 岁,p=0.01)。末次生育与受体阳性患者的死亡风险相关(HR=≤4 岁比≥10 岁,p=0.004)。
这些结果表明,初潮和产次的时间对患者的生存有显著影响,为理解女性生命历程与乳腺癌结局之间的关系提供了线索。