McGee Jacob, Giannakeas Vasily, Karlan Beth, Lubinski Jan, Gronwald Jacek, Rosen Barry, McLaughlin John, Risch Harvey, Sun Ping, Foulkes William D, Neuhausen Susan L, Kotsopoulos Joanne, Narod Steven A
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Western University, London, ON, Canada.
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
Gynecol Oncol. 2017 May;145(2):346-351. doi: 10.1016/j.ygyno.2017.02.032. Epub 2017 Mar 14.
Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening.
First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality.
Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer.
Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer.
为未受影响的BRCA突变携带者提供预防性乳房手术和MRI筛查。这两种方式的临床益处尚未在有卵巢癌病史的突变携带者中进行评估。因此,我们试图确定患有卵巢癌的BRCA突变携带者是否能从预防性乳房切除术或MRI筛查中获益。
首先,对来自加拿大安大略省的178名BRCA突变携带者队列估计卵巢癌患者的年死亡率。接下来,使用一个有509名患有卵巢癌的BRCA突变携带者的国际登记处来估计患乳腺癌的精算风险。进行了一系列模拟,以评估与乳房切除术和基于MRI的乳房监测相关的全因死亡概率的降低。使用Cox比例风险模型来评估乳房切除术和MRI筛查对乳腺癌发病率以及全因死亡率的影响。
509名患者中有20名(3.9%)在卵巢癌诊断后的十年内患乳腺癌。在卵巢癌及其他死亡原因存活的条件下,诊断后十年患乳腺癌的精算风险为7.8%。根据我们的模拟结果,在所有50岁时被诊断为III/IV期卵巢癌的BRCA突变携带者患者中,MRI可使80岁前死亡的几率降低不到1%,乳房切除术可使该几率降低不到2%。对于卵巢癌后已存活10年的女性以及患有I期或II期卵巢癌的女性,观察到MRI或乳房切除术在生存方面有更大改善。
在没有乳腺癌个人病史的携带BRCA突变的卵巢癌患者中,除那些卵巢癌无复发存活十年的患者以及早期卵巢癌患者外,预防性乳房切除术和MRI筛查均无必要。