Studies on characteristics and prognosis of breast cancer with late recurrence

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10531
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hokkaido University
• Principal Investigator: Yamashita Hiroko 北海道大学, 大学病院, 教授 (70332947)
• Co-Investigator(Kenkyū-buntansha): 馬場 基 北海道大学, 大学病院, 助教 (90724980)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 乳癌 / トランスレーショナルリサーチ

Outline of Final Research Achievements

PIK3CA is the most frequent mutated gene in estrogen receptor (ER)-positive early breast cancers, and PIK3CA mutation status is reported to affect activation of AKT and ERα. PIK3CA mutations were detected in 47% in premenopausal women and 47% in postmenopausal women. Postmenopausal women with PIK3CA wild-type tumors had significantly worse disease-free survival than patients with PIK3CA mutant tumors. Low levels of phosphorylation of AKT serine (Ser) 473 (AKT phospho-Ser473) and high levels of ERα Ser167 (ERα phospho-Ser167) were strongly associated with increased disease-free survival in postmenopausal women. Evaluation of ERα activation, in addition to PIK3CA mutation status, might be helpful in identifying patients who are likely to benefit from endocrine therapy alone versus those who are not in postmenopausal ER-positive early breast cancer.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

エストロゲン受容体陽性乳癌では初回治療後5年以降に再発（晩期再発）する症例が存在する。晩期再発乳癌は増殖が遅く培養細胞が樹立できず、晩期再発のメカニズムは未だ解明されていない。本研究で晩期再発乳癌に特徴的な乳癌組織における遺伝子変異および遺伝子発現を同定することにより、晩期再発のメカニズムの解明に繋がり、新たな治療戦略をもたらす。晩期再発乳癌の予後予測因子の同定により、術後長期の内分泌療法の適応症例が明確となる。