Fagerholm Rainer, Faltinova Maria, Aaltonen Kirsi, Aittomäki Kristiina, Heikkilä Päivi, Halttunen-Nieminen Mervi, Nevanlinna Heli, Blomqvist Carl
Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, PO Box 700, 00029 HUS,, Helsinki, Finland.
Department of Oncology, Helsinki University Hospital and University of Helsinki, PO Box 180, 00029 HUS,, Helsinki, Finland.
Fam Cancer. 2018 Jul;17(3):321-331. doi: 10.1007/s10689-017-0046-2.
Long term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast cancer (BCS), distant disease free survival (DDFS), and local recurrence free survival (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95% CI 0.41-0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40-0.85; p = 0.005), with a consistent but not statistically significant effect in LRFS. This effect was not seen in familial cases (HR > 1.0), and family history was found to interact with HT in BCS (p = 0.0067) (BC-death) and DDFS (p = 0.0070). There was phenotypic heterogeneity between HT-associated tumors in familial and non-familial cases, particularly on estrogen receptor (ER) status, although the interaction between HT and family history appears to be at least partially independent of these markers (p = 0.0370 after adjustment for standard prognostic factors). If confirmed by further studies, our results suggest that family history should be taken into consideration in clinical counseling before beginning a HT regimen.
据报道，长期使用绝经后激素疗法（HT）会增加患乳腺癌的风险。另一方面，观察性研究表明，在接受HT治疗期间诊断出的乳腺癌可能预后更佳。虽然家族史是乳腺癌的一个风险因素，并且遗传因素也会影响预后，但家族史与HT联合使用的作用鲜少被研究。我们调查了584例（267例接受暴露）家族性乳腺癌病例和952例（460例接受暴露）非家族性乳腺癌病例中HT、家族史与预后之间的关系，采用了三个生存终点：乳腺癌死亡（BCS）、无远处疾病生存（DDFS）和无局部复发生存（LRFS）。在非家族性病例中，HT与更好的BCS（风险比[HR] 0.63，95%置信区间[CI] 0.41 - 0.94；p = 0.025）和DDFS（HR 0.58，95% CI 0.40 - 0.85；p = 0.005）相关，在LRFS中也有一致但无统计学意义的影响。在家族性病例中未观察到这种效应（HR > 1.0），并且发现家族史在BCS（p = 0.0067）（乳腺癌死亡）和DDFS（p = 0.0070）方面与HT存在相互作用。家族性和非家族性病例中与HT相关的肿瘤存在表型异质性，特别是在雌激素受体（ER）状态方面，尽管HT与家族史之间的相互作用似乎至少部分独立于这些标志物（在调整标准预后因素后p = 0.0370）。如果进一步研究证实，我们的结果表明，在开始HT治疗方案之前的临床咨询中应考虑家族史。
