Eccles Diana, Gerty Sue, Simmonds Peter, Hammond Victoria, Ennis Sarah, Altman Douglas G
Somers Cancer Sciences Building Mail Point 824, Southampton University Hospitals NHS Trust, Tremona Road, Southampton SO16 6YA, UK.
BMC Cancer. 2007 Aug 15;7:160. doi: 10.1186/1471-2407-7-160.
Young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other) cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors.
METHODS/DESIGN: The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period.
Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward.
与一般乳腺癌患者相比，年轻女性乳腺癌患者更有可能具有该疾病的遗传易感性。已知遗传易感性会增加新发原发性乳腺癌（及其他癌症）的风险。从文献中尚不清楚在为首次诊断原发性乳腺癌的年轻女性制定辅助治疗方案时是否应考虑遗传状态。POSH研究的主要目的是确定遗传状态是否独立于已知的预后因素影响原发性乳腺癌的预后。
方法/设计：该研究是一项前瞻性队列研究，招募3000名在乳腺癌诊断时年龄为40岁或以下的女性；招募期为2001年6月1日至2007年12月31日。在研究入组时获得书面知情同意。通过问卷收集家族史和已知的流行病学风险数据。收集有关诊断、治疗和临床病程的临床信息并储存血液。在第一年之后每年收集随访数据。另一个招募类别包括年龄在41至50岁之间且被发现为BRCA1或BRCA2基因携带者并在研究招募期间被诊断为首次患乳腺癌的女性。
效能估计基于队列中10%携带BRCA1基因突变。对一组试点研究参与者进行的初步BRCA1和BRCA2突变分析证实，我们应有97%的效能检测基因携带者与散发的年轻发病病例之间事件发生率10%的差异。大多数招募的患者（>80%）接受含蒽环类药物的辅助化疗方案，这使得计划分析更加直接。
