Ursin G, Bernstein L, Lord S J, Karim R, Deapen D, Press M F, Daling J R, Norman S A, Liff J M, Marchbanks P A, Folger S G, Simon M S, Strom B L, Burkman R T, Weiss L K, Spirtas R
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Br J Cancer. 2005 Aug 8;93(3):364-71. doi: 10.1038/sj.bjc.6602712.
Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.
生殖因素与降低乳腺癌风险相关，但对于其是否对乳腺癌亚型具有差异保护作用，人们了解较少。假设生殖因素通过激素机制发挥作用，那么它们应主要对表达雌激素（ER）和孕激素（PR）受体的癌症起到保护作用。我们利用美国国立儿童健康与人类发展研究所女性避孕与生殖经历（CARE）研究的数据，研究了生殖因素对由激素受体状态以及组织学定义的肿瘤亚组的影响，该研究是一项关于乳腺癌的多中心病例对照研究。我们使用多变量无条件逻辑回归方法估计比值比（OR）和95%置信区间（CI）作为相对风险的度量。多产和早育与ER + PR +肿瘤的相对风险降低相关（趋势P值分别为0.0001和0.01），但与ER - PR -肿瘤无关（趋势P值分别为0.27和0.85），而母乳喂养时长与受体阳性肿瘤（趋势P值=0.0002）和受体阴性肿瘤的相对风险降低均相关（P = 0.0004）。我们的结果在基于年龄和种族的女性亚组中是一致的。尽管多产对混合性导管小叶肿瘤的保护作用最强，但按组织学亚型分析，我们发现差异不大。我们的结果表明，产次和初产年龄仅与受体阳性肿瘤风险降低相关，而哺乳与受体阳性和阴性肿瘤风险降低均相关。这表明产次和哺乳通过不同机制发挥作用。本研究还表明，生殖因素对小叶和导管起源的乳腺肿瘤具有相似的保护作用。
