臨床外科63巻8号

2008年08月発行

特集 St. Gallen 2007に基づいた乳癌テーラーメイド補助療法

Triple negativeでの補助療法と今後の展望

著者： 髙田正泰¹ 戸井雅和¹

所属機関： ¹京都大学大学院医学研究科外科学講座　乳腺外科学

ページ範囲：P.1087 - P.1091

要旨：エストロゲン受容体陰性，プロゲステロン受容体陰性，HER2陰性のいわゆる“triple negative”乳癌は，治療選択肢の乏しさとその生物学的特徴などから予後不良の乳癌とされている．なかでも半数以上を占めるといわれるbasal-likeは，特に予後が不良である．しかしながら，これらに対する特異的な治療法はまだ確立されておらず，St. Gallen 2007でも明示されていない．本稿では，triple negativeあるいはbasal-like乳癌の臨床的・病理組織学的特徴，および分子生物学的アプローチによる治療戦略と現在進行中の臨床試験を紹介するとともに，今後の展望について述べる．

参考文献

1）Sørlie T, Perou CM, Tibshirani R, et al：Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98：10869-10874, 2001

2）Nielsen TO, Hsu FD, Jensen K, et al：Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10：5367-5374, 2004

3）Rakha EA, EI-Sayed ME, Green AR, et al：Prognostic markers in triple-negative breast cancer. Cancer 109：25-32, 2007

4）Tischkowitz M, Brunet JS, Bégin LR, et al：Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer 7：134, 2007

5）Livasy CA, Karaca G, Nanda R, et al：Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19：264-271, 2006

6）Foulkes WD, Brunet JS, Stefansson IM, et al：The prognostic implication of the basal-like（cyclineE high/p27 low/p53＋/glomeruloid-microvascular-proliferation＋）phenotype of BRCA1-related breast cancer. Cancer Res 64：830-835, 2004

7）Turner N, Tutt A, Ashworth A：Hallmarks of‘BRCAness’in sporadic cancers. Nat Rev Cancer 4：814-819, 2004

8）Turner NC, Reis-Filho JS, Russel AM, et al：BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26：2126-2132, 2007

9）Yang WT, Dryden M, Broglio K, et al：Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat：2007 NOV 17, first published online

10）Chen JH, Agrawal G, Feig B, et al：Triple-negative breast cancer：MRI features in 29 patients. Ann Oncol 18：2042-2043, 2007

11）Dent R, Trudeau M, Pritchard KI, et al：Triple-negative breast cancer：clinical features and patterns of recurrence. Clin Cancer Res 13：4429-4434, 2007

12）Banerjee S, Reis-Filho JS, Ashley S, et al：Basal-like breast carcinomas：clinical outcome and response to chemotherapy. J Clin Pathol 59：729-735, 2006

13）Liedtke C, Mazouni C, Hess KR, et al：Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26：1275-1281, 2008

14）Carey LA, Dees EC, Sawyer L, et al：The triple negative paradox：primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13：2329-2334, 2007

15）Rouzier R, Perou CM, Symmans WF, et al：Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11：5678-5685, 2005

16）Husain A, He G, Venkatraman ES, et al：BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum（Ⅱ）. Cancer Res 58：1120-1123, 1998

17）Lafarge S, Sylvain V, Ferrara M, et al：Inhibition of BRCA1 leads to increased chemoresistance to microtubule-interfering agents, an effect that involves the JNK pathway. Oncogene 20：6597-6606, 2001

18）Tassone R, Tagliaferri P, Perricelli A, et al：BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer 88：1285-1291, 2003

19）Quinn JE, Kennedy RD, Mullan PB, et al：BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 63：6221-6228, 2003

20）Couzin J：Choices―and uncertainties―for women with BRCA mutations. Science 302：592, 2003

21）Tutt AN, Lord CJ, McCabe N, et al：Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol 70：139-148, 2005

22）Farmer H, McCabe N, Lord CJ, et al：Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434：917-921, 2005

23）Mullan PB, Quinn JE, Gilomore PM, et al：BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule agents. Ongcogene 20：6123-6131, 2001

24）Adjei AA, Hidalgo M：Treating cancer by blocking cell signals. J Clin Oncol 23：5279-5280, 2005

25）Reis-Filho JS, Tutt AN：Triple negative tumours：a critical review. Histopathology 52：108-118, 2008