Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Breast Cancer Res. 2010;12(3):R35. doi: 10.1186/bcr2589. Epub 2010 Jun 18.
Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia.
Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend < 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors.
These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration.
尽管妊娠相关因素（如未生育和首次足月妊娠年龄较晚）是浸润性乳腺癌的明确危险因素，但这些因素在乳腺癌发展的自然史中的作用仍不清楚。
在参加加利福尼亚教师研究（CTS）的 52464 名绝经后妇女中，624 名被诊断患有乳腺癌原位（CIS），2828 名患有浸润性乳腺癌，诊断时间为 1995 年至 2007 年。采用多变量 Cox 比例风险回归方法估计与生育次数、首次足月妊娠年龄、母乳喂养、妊娠恶心或呕吐以及先兆子痫相关的相对风险。
与从未怀孕的女性相比，足月妊娠次数的增加与乳腺癌 CIS 和浸润性乳腺癌的风险降低呈正相关（均 P 趋势<0.01）。足月妊娠 4 次或以上的女性患乳腺癌 CIS 的风险降低 31%（RR=0.69，95%CI=0.51 至 0.93），浸润性乳腺癌风险降低 18%（RR=0.82，95%CI=0.72 至 0.94）。首次足月妊娠年龄在 35 岁或以上的多产妇患乳腺癌 CIS 的风险增加 118%（RR=2.18，95%CI=1.36 至 3.49），浸润性乳腺癌的风险增加 27%（RR=1.27，95%CI=0.99 至 1.65），首次足月妊娠年龄在 21 岁之前的女性。此外，生育次数与雌激素受体阳性（ER+）或 ER+/孕激素受体阳性（PR+）浸润性乳腺癌的风险呈负相关，而首次足月妊娠年龄与 ER+或 ER+/PR+浸润性乳腺癌的风险呈正相关。这些因素与 ER-（ER-）或 ER-/PR-浸润性乳腺癌的风险均无统计学显著相关性，亚组间的异质性检验未达到统计学显著性。其他妊娠相关因素未发现明显关联。
这些结果提供了一些流行病学证据，表明生育次数和首次足月妊娠年龄与绝经后妇女乳腺癌的发生有关。这些因素在原位与浸润性、激素受体阳性与阴性乳腺癌风险中的作用值得进一步探讨。
