今日の臨床サポート

遺伝性乳癌・卵巣癌症候群(HBOC)

著者: 森美樹 昭和大学病院ブレストセンター 乳腺外科、自由が丘みきブレストクリニック

監修: 中村清吾 昭和大学医学部外科学講座乳腺外科学部門

著者校正/監修レビュー済:2021/10/27
参考ガイドライン:
  1. 日本乳癌学会:乳癌診療ガイドライン 1 治療編 2018年版
  1. 日本乳癌学会:乳癌診療ガイドライン 2 疫学・診断編 2018年版
  1. 日本乳癌学会:患者さんのための乳がん診療ガイドライン 2014年版
  1. NCCN guideline:Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Version: 1.2022
  1. 日本遺伝性乳癌卵巣癌総合診療制度機構遺伝性乳癌卵巣癌(HBOC)診療ガイドライン2021年版
患者向け説明資料

概要・推奨   

  1. BRCA遺伝学的検査を推奨するクライエント:①発症、未発症に関わらず家系内でBRCA1/BRCA2の病的/おそらく病的バリアントが確認されている。②乳癌、卵巣癌、前立腺癌、膵癌を発症しており、BRCA1/2に一定以上の割合で病的バリアントを保持すると推定される。③PARP阻害薬に対するコンパニオン診断の適応基準を満たす。④がんゲノムプロファイリング検査で、BRCA1/2の生殖細胞系列の病的バリアント保持が疑われる。
  1. 乳癌既発症者における対側リスク低減乳房切除術は、乳癌発症リスク低減効果のみならず、全生存率改善効果が認められていることから、本人の意思に基づき遺伝カウンセリング体制などの環境が整備されている条件下で実施を強く推奨する。
  1. BRCA1あるいはBRCA2遺伝子変異をもつ挙児希望のない女性に対してリスク低減卵管卵巣摘出術の実施を強く推奨する。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
森美樹 : 特に申告事項無し[2021年]
監修:中村清吾 : 講演料(アストラゼネカ,第一三共,中外製薬),研究費・助成金など(CESデカルト,第一三共,シスメックス,アストラゼネカ,島津製作所,大鵬薬品工業),奨学(奨励)寄付など(エーザイ,コニカミノルタ,大鵬薬品工業,中外製薬)[2021年]

改訂のポイント:
  1. 最新のNCCNガイドラインに基づきHBOC検査基準と治療方法の決定を改訂した。今年発行された遺伝性乳癌卵巣癌診療ガイドラインに基づき遺伝子検査を推奨する対象とアルゴリズムを追記した。

病態・疫学・診察

疾患情報  
  1. 全乳癌のうち、遺伝要因が関係しているのは5~10%であり、全卵巣癌のうち遺伝要因が関係しているのは15%以下とされる[1][2][3][4]
  1. 遺伝性乳癌や卵巣癌のうち、多くはBRCA1あるいはBRCA2遺伝子の病的変異であり、そのほかTP53遺伝子の病的変異によるLi-Fraumeni症候群や、PTEN遺伝子の病的変異によるCowden症候群などがある。このうち、BRCA1BRCA2遺伝子に病的変異があるものを遺伝性乳癌・卵巣癌症候群(Hereditary Breast and Ovarian Cancer syndrome、HBOC)という。
  1. 常染色体優性遺伝である。
  1. BRCA1:染色体17q21に存在する。BRCA1がコードする蛋白は、細胞周期やDNA損傷の修復に重要な役割を持つ。
  1. BRCA2:染色体13q12に存在する。BRCA2がコードするタンパクは、BRCA1蛋白と結合して、DNA損傷に応答する経路に関与するとされている。
  1. BRCA1またはBRCA2遺伝子のいずれかに病的変異がある場合、乳癌の生涯の発症リスクは65~74%、卵巣癌の生涯の発症リスクはBRCA1遺伝子の病的変異がある場合39~46%、BRCA2遺伝子の病的変異がある場合12~20%である[5]
問診・診察のポイント  
  1. 本人の癌の既往の聴取

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: William D Foulkes
雑誌名: N Engl J Med. 2008 Nov 13;359(20):2143-53. doi: 10.1056/NEJMra0802968.
Abstract/Text
PMID 19005198  N Engl J Med. 2008 Nov 13;359(20):2143-53. doi: 10.1056・・・
著者: Mary B Daly, Jennifer E Axilbund, Saundra Buys, Beth Crawford, Carolyn D Farrell, Susan Friedman, Judy E Garber, Salil Goorha, Stephen B Gruber, Heather Hampel, Virginia Kaklamani, Wendy Kohlmann, Allison Kurian, Jennifer Litton, P Kelly Marcom, Robert Nussbaum, Kenneth Offit, Tuya Pal, Boris Pasche, Robert Pilarski, Gwen Reiser, Kristen Mahoney Shannon, Jeffrey R Smith, Elizabeth Swisher, Jeffrey N Weitzel, National Comprehensive Cancer Network
雑誌名: J Natl Compr Canc Netw. 2010 May;8(5):562-94.
Abstract/Text
PMID 20495085  J Natl Compr Canc Netw. 2010 May;8(5):562-94.
著者: Steven A Narod
雑誌名: Nat Rev Clin Oncol. 2010 Dec;7(12):702-7. doi: 10.1038/nrclinonc.2010.166. Epub 2010 Oct 19.
Abstract/Text Genetic testing for BRCA1 and BRCA2 mutations is gaining acceptance in clinical oncology worldwide and may help target unaffected high-risk women for prevention and for close surveillance. Annual screening with MRI seems to be an effective surveillance strategy, but the long term follow-up of women with small MRI-detected breast cancers is necessary to establish its ultimate value. Women with cancer and a BRCA mutation may benefit from tailored treatments, such as cisplatin or olaparib. The treatment goals for a woman with a BRCA-associated breast cancer should be to prevent recurrence of the initial cancer and to prevent second primary breast and ovarian cancers. Mutations in BRCA1 and BRCA2 are presented throughout the world and it is important that the benefits of genetic testing and of targeted therapies be extended to women who live outside of North America and Western Europe.

PMID 20956982  Nat Rev Clin Oncol. 2010 Dec;7(12):702-7. doi: 10.1038/・・・
著者: John O Schorge, Susan C Modesitt, Robert L Coleman, David E Cohn, Noah D Kauff, Linda R Duska, Thomas J Herzog
雑誌名: Gynecol Oncol. 2010 Oct;119(1):7-17. doi: 10.1016/j.ygyno.2010.06.003. Epub 2010 Aug 7.
Abstract/Text Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of low prevalence. The etiology remains poorly understood. Numerous risk factors have been identified, the most prominent involving an inherited predisposition in 10% of cases. Women with germline mutations associated with Hereditary Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to 46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best method to prevent ovarian cancer in these high-risk women. Significant risk reduction is also seen in the general population who use oral contraceptives. Since up to 89% patients with early-stage disease have symptoms prior to diagnosis, increased awareness of the medical community may facilitate further workup in patients who otherwise would have had a delay. Despite enormous effort, there is no proof that routine screening for ovarian cancer in either the high-risk or general populations with serum markers, sonograms, or pelvic examinations decreases mortality. Further evaluation is needed to determine whether any novel biomarkers, or panels of markers, have clinical utility in early detection. Prospective clinical trials have to be designed and completed prior to offering of any of these new diagnostic tests. CA125 is currently the only biomarker recommended for monitoring of therapy as well as detection of recurrence. This commentary provides an overview on the background, screening and surveillance of ovarian cancer.

Copyright © 2010 Elsevier Inc. All rights reserved.
PMID 20692025  Gynecol Oncol. 2010 Oct;119(1):7-17. doi: 10.1016/j.ygy・・・
著者: American College of Obstetricians and Gynecologists, ACOG Committee on Practice Bulletins--Gynecology, ACOG Committee on Genetics, Society of Gynecologic Oncologists
雑誌名: Obstet Gynecol. 2009 Apr;113(4):957-66. doi: 10.1097/AOG.0b013e3181a106d4.
Abstract/Text Hereditary breast and ovarian cancer syndrome is an inherited cancer-susceptibility syndrome. The hallmarks of this syndrome are multiple family members with breast cancer or ovarian cancer or both, the presence of both breast cancer and ovarian cancer in a single individual, and early age of breast cancer onset. Clinical genetic testing for gene mutations allows physicians to more precisely identify women who are at substantial risk of breast cancer and ovarian cancer. For these individuals, screening and prevention strategies can be instituted to reduce their risks. Obstetricians and gynecologists play an important role in the identification and management of women with hereditary breast and ovarian cancer syndrome.

PMID 19305347  Obstet Gynecol. 2009 Apr;113(4):957-66. doi: 10.1097/AO・・・
著者: Xiao Li, Ran You, Xinwei Wang, Congxin Liu, Zicheng Xu, Jin Zhou, Bin Yu, Ting Xu, Hongzhou Cai, Qing Zou
雑誌名: Clin Cancer Res. 2016 Aug 1;22(15):3971-81. doi: 10.1158/1078-0432.CCR-15-1465. Epub 2016 Mar 15.
Abstract/Text PURPOSE: To systematically investigate the effectiveness of prophylactic surgeries (PS) implemented in women carrying BRCA1/2 mutations.
EXPERIMENTAL DESIGN: The PubMed database was searched till August 2014 and 15 studies met the inclusion criteria. Fixed- or random-effects models were conducted according to study heterogeneity. We calculated the pooled relative risks (RR) for cancer risk or mortality along with 95% confidence intervals (CI).
RESULTS: Prophylactic bilateral salpingo-oophorectomy (PBSO) and bilateral prophylactic mastectomy (BPM) were both associated with a decreased breast cancer risk in BRCA1/2 mutation carriers (RR, 0.552; 95% CI, 0.448-0.682; RR, 0.114; 95% CI, 0.041-0.317, respectively). Similar findings were observed in BRCA1 and BRCA2 mutation carriers separately. Moreover, contralateral prophylactic mastectomy (CPM) significantly decreased contralateral breast cancer incidence in BRCA1/2 mutation carriers (RR, 0.072; 95% CI, 0.035-0.148). Of note, PBSO was associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers without breast cancer (HR, 0.349; 95% CI, 0.190-0.639) and those with breast cancer (HR, 0.432; 95% CI, 0.318-0.588). In addition, all-cause mortality was significantly lower for patients with CPM than those without (HR, 0.512; 95% CI, 0.368-0.714). However, BPM was not significantly associated with reduced all-cause mortality. Data were insufficient to obtain separate estimates of survival benefit with PS in BRCA1 or BRCA2 mutation carriers.
CONCLUSIONS: BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971-81. ©2016 AACR.

©2016 American Association for Cancer Research.
PMID 26979395  Clin Cancer Res. 2016 Aug 1;22(15):3971-81. doi: 10.115・・・
著者: D Gareth R Evans, Sarah L Ingham, Andrew Baildam, Gary L Ross, Fiona Lalloo, Iain Buchan, Anthony Howell
雑誌名: Breast Cancer Res Treat. 2013 Jul;140(1):135-42. doi: 10.1007/s10549-013-2583-1. Epub 2013 Jun 20.
Abstract/Text BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2 mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0-13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17-0.80, p = 0.008)-CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.

PMID 23784379  Breast Cancer Res Treat. 2013 Jul;140(1):135-42. doi: 1・・・
著者: T C van Sprundel, M K Schmidt, M A Rookus, R Brohet, C J van Asperen, E J Th Rutgers, L J Van't Veer, R A E M Tollenaar
雑誌名: Br J Cancer. 2005 Aug 8;93(3):287-92. doi: 10.1038/sj.bjc.6602703.
Abstract/Text The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I-IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

PMID 16052221  Br J Cancer. 2005 Aug 8;93(3):287-92. doi: 10.1038/sj.b・・・
著者: Kelly Metcalfe, Shelley Gershman, Parviz Ghadirian, Henry T Lynch, Carrie Snyder, Nadine Tung, Charmaine Kim-Sing, Andrea Eisen, William D Foulkes, Barry Rosen, Ping Sun, Steven A Narod
雑誌名: BMJ. 2014 Feb 11;348:g226. Epub 2014 Feb 11.
Abstract/Text OBJECTIVE: To compare the survival rates of women with BRCA associated breast cancer who did and did not undergo mastectomy of the contralateral breast.
DESIGN: Retrospective analysis.
SETTING: 12 cancer genetics clinics.
PARTICIPANTS: 390 women with a family history of stage I or II breast cancer who were carriers of BRCA1 and BRCA2 mutations and initially treated with unilateral or bilateral mastectomy. 181 patients had mastectomy of the contralateral breast. Patients were followed for up to 20 years from diagnosis.
MAIN OUTCOME MEASURE: Death from breast cancer.
RESULTS: 79 women died of breast cancer in the follow-up period (18 in the bilateral mastectomy group and 61 in the unilateral mastectomy group). The median follow-up time was 14.3 years (range 0.1-20.0 years). At 20 years the survival rate for women who had mastectomy of the contralateral breast was 88% (95% confidence interval 83% to 93%) and for those who did not was 66% (59% to 73%). In a multivariable analysis, controlling for age at diagnosis, year of diagnosis, treatment, and other prognostic features, contralateral mastectomy was associated with a 48% reduction in death from breast cancer (hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P=0.03). In a propensity score adjusted analysis of 79 matched pairs, the association was not significant (0.60, 0.34 to 1.06; P=0.08). Based on these results, we predict that of 100 women treated with contralateral mastectomy, 87 will be alive at 20 years compared with 66 of 100 women treated with unilateral mastectomy.
CONCLUSIONS: This study suggests that women who are positive for BRCA mutations and who are treated for stage I or II breast cancer with bilateral mastectomy are less likely to die from breast cancer than women who are treated with unilateral mastectomy. Given the small number of events in this cohort, further research is required to confirm these findings.

PMID 24519767  BMJ. 2014 Feb 11;348:g226. Epub 2014 Feb 11.
著者: Bernadette A M Heemskerk-Gerritsen, Matti A Rookus, Cora M Aalfs, Margreet G E M Ausems, Johanna M Collée, Liesbeth Jansen, C Marleen Kets, Kristien B M I Keymeulen, Linetta B Koppert, Hanne E J Meijers-Heijboer, Thea M Mooij, Rob A E M Tollenaar, Hans F A Vasen, HEBON, Maartje J Hooning, Caroline Seynaeve
雑誌名: Int J Cancer. 2015 Feb 1;136(3):668-77. doi: 10.1002/ijc.29032. Epub 2014 Jul 8.
Abstract/Text Data on survival of BRCA1/2-associated primary breast cancer (PBC) patients who opt for subsequent contralateral risk-reducing mastectomy (CRRM) are scarce and inconsistent. We examined the efficacy of CRRM on overall survival in mutation carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583 BRCA-associated PBC patients, being diagnosed between 1980 and 2011. Over time, 242 patients (42%) underwent CRRM and 341 patients (58%) remained under surveillance. Survival analyses were performed using Cox models, with CRRM as a time-dependent covariate. The median follow-up after PBC diagnosis was 11.4 years. In the CRRM group, four patients developed contralateral breast cancer (2%), against 64 patients (19%) in the surveillance group (p < 0.001). The mortality was lower in the CRRM group than in the surveillance group (9.6 and 21.6 per 1000 person-years of observation, respectively; adjusted hazard ratio 0.49, 95% confidence interval 0.29-0.82). Survival benefit was especially seen in young PBC patients (<40 years), in patients having a PBC with differentiation grade 1/2 and/or no triple-negative phenotype, and in patients not treated with adjuvant chemotherapy. We conclude that CRRM is associated with improved overall survival in BRCA1/2 mutation carriers with a history of PBC. Further research is warranted to develop a model based on age at diagnosis and tumour and treatment characteristics that can predict survival benefit for specific subgroups of patients, aiming at further personalized counselling and improved decision making.

© 2014 UICC.
PMID 24947112  Int J Cancer. 2015 Feb 1;136(3):668-77. doi: 10.1002/ij・・・
著者: Amy Finch, Mario Beiner, Jan Lubinski, Henry T Lynch, Pal Moller, Barry Rosen, Joan Murphy, Parviz Ghadirian, Eitan Friedman, William D Foulkes, Charmaine Kim-Sing, Teresa Wagner, Nadine Tung, Fergus Couch, Dominique Stoppa-Lyonnet, Peter Ainsworth, Mary Daly, Babara Pasini, Ruth Gershoni-Baruch, Charis Eng, Olufunmilayo I Olopade, Jane McLennan, Beth Karlan, Jeffrey Weitzel, Ping Sun, Steven A Narod, Hereditary Ovarian Cancer Clinical Study Group
雑誌名: JAMA. 2006 Jul 12;296(2):185-92. doi: 10.1001/jama.296.2.185.
Abstract/Text CONTEXT: Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort.
OBJECTIVES: To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy.
DESIGN, SETTING, AND PARTICIPANTS: Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up.
INTERVENTION: Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not.
MAIN OUTCOME MEASURE: The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates.
RESULTS: After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003).
CONCLUSION: Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

PMID 16835424  JAMA. 2006 Jul 12;296(2):185-92. doi: 10.1001/jama.296.・・・
著者: Susan M Domchek, Tara M Friebel, Christian F Singer, D Gareth Evans, Henry T Lynch, Claudine Isaacs, Judy E Garber, Susan L Neuhausen, Ellen Matloff, Rosalind Eeles, Gabriella Pichert, Laura Van t'veer, Nadine Tung, Jeffrey N Weitzel, Fergus J Couch, Wendy S Rubinstein, Patricia A Ganz, Mary B Daly, Olufunmilayo I Olopade, Gail Tomlinson, Joellen Schildkraut, Joanne L Blum, Timothy R Rebbeck
雑誌名: JAMA. 2010 Sep 1;304(9):967-75. doi: 10.1001/jama.2010.1237.
Abstract/Text CONTEXT: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.
OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and prior cancer status.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.
MAIN OUTCOMES MEASURES: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.
RESULTS: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).
CONCLUSIONS: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

PMID 20810374  JAMA. 2010 Sep 1;304(9):967-75. doi: 10.1001/jama.2010.・・・
著者: Amy P M Finch, Jan Lubinski, Pål Møller, Christian F Singer, Beth Karlan, Leigha Senter, Barry Rosen, Lovise Maehle, Parviz Ghadirian, Cezary Cybulski, Tomasz Huzarski, Andrea Eisen, William D Foulkes, Charmaine Kim-Sing, Peter Ainsworth, Nadine Tung, Henry T Lynch, Susan Neuhausen, Kelly A Metcalfe, Islay Thompson, Joan Murphy, Ping Sun, Steven A Narod
雑誌名: J Clin Oncol. 2014 May 20;32(15):1547-53. doi: 10.1200/JCO.2013.53.2820. Epub 2014 Feb 24.
Abstract/Text PURPOSE: The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort.
PATIENTS AND METHODS: Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses.
RESULTS: After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001).
CONCLUSION: Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.

© 2014 by American Society of Clinical Oncology.
PMID 24567435  J Clin Oncol. 2014 May 20;32(15):1547-53. doi: 10.1200/・・・
著者: Sarah L Ingham, Matthew Sperrin, Andrew Baildam, Gary L Ross, Richard Clayton, Fiona Lalloo, Iain Buchan, Anthony Howell, D Gareth R Evans
雑誌名: Breast Cancer Res Treat. 2013 Dec;142(3):611-8. doi: 10.1007/s10549-013-2765-x. Epub 2013 Nov 20.
Abstract/Text The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.

PMID 24249359  Breast Cancer Res Treat. 2013 Dec;142(3):611-8. doi: 10・・・

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