Kanaizumi Hirofumi, Higashi Chihiro, Tanaka Yumiko, Hamada Mika, Shinzaki Wataru, Azumi Tatsuya, Hashimoto Yukihiko, Inui Hiroki, Houjou Toshiya, Komoike Yoshifumi
Division of Breast and Endocrine Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan.
Oncol Lett. 2019 Feb;17(2):1962-1968. doi: 10.3892/ol.2018.9759. Epub 2018 Nov 26.
Oestrogen receptor (ER)-positive, metachronous, contralateral breast cancer (MCBC) sometimes develops during or soon after completion of hormone therapy (HT), but it is uncertain whether it is HT-resistant. We examined the association between ER-positive second cancer and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways, which are associated with HT resistance. We examined the treatment-free interval (time after completion of HT for initial cancer) in 41 patients with ER-positive MCBC with a history of adjuvant HT for initial cancer (HT group), and initial-to-second period duration (time after operation of initial cancer to onset of second cancer) in 17 patients with ER-positive MCBC in whom adjuvant HT was not applied to the initial tumour (control group or no HT group). Phosphorylated S6 (pS6) and phosphorylated MAPK (pMAPK) were used as indicators of PI3K/Akt/mTOR and MAPK pathway activity, respectively. Tumours were classified as showing negative, positive or strongly positive staining, and the correlation between staining and treatment-free interval or initial-to-second period duration was evaluated using the Spearman's rank correlation coefficient (ρ). Treatment-free interval and pS6 staining showed a negative correlation (ρ=-0.5355; P=0.0003) in the HT group. There was no correlation between initial-to-second period duration and pS6 staining in the no HT group (ρ=-0.0814; P=0.756). There was no correlation between pMAPK signalling and the treatment-free interval in the HT group (ρ=-0.1560; P=0.330) or the initial-to-second period duration in the no HT group (ρ=-0.0116; P=0.965). Development of a second ER-positive cancer during or soon after completion of HT for the initial cancer may be associated with activation of the PI3K/Akt/mTOR pathway. Care should be taken during follow-up and when selecting adjuvant therapy for second cancer.
雌激素受体（ER）阳性的异时性对侧乳腺癌（MCBC）有时会在激素治疗（HT）期间或结束后不久发生，但尚不确定其是否对HT耐药。我们研究了ER阳性的第二原发癌与磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素哺乳动物靶蛋白（mTOR）和丝裂原活化蛋白激酶（MAPK）通路激活之间的关联，这些通路与HT耐药相关。我们研究了41例有初始癌症辅助HT病史的ER阳性MCBC患者的无治疗间期（初始癌症HT结束后的时间）（HT组），以及17例初始肿瘤未接受辅助HT的ER阳性MCBC患者的初次到第二次发病时长（初始癌症手术后到第二次癌症发病的时间）（对照组或无HT组）。磷酸化S6（pS6）和磷酸化MAPK（pMAPK）分别用作PI3K/Akt/mTOR和MAPK通路活性的指标。肿瘤被分类为显示阴性、阳性或强阳性染色，并使用Spearman等级相关系数（ρ）评估染色与无治疗间期或初次到第二次发病时长之间的相关性。HT组中，无治疗间期与pS6染色呈负相关（ρ=-0.5355；P=0.0003）。无HT组中初次到第二次发病时长与pS6染色之间无相关性（ρ=-0.0814；P=0.756）。HT组中pMAPK信号与无治疗间期之间无相关性（ρ=-0.1560；P=0.330），无HT组中pMAPK信号与初次到第二次发病时长之间也无相关性（ρ=-0.0116；P=0.965）。在初始癌症HT期间或结束后不久发生第二例ER阳性癌症可能与PI3K/Akt/mTOR通路的激活有关。在随访期间以及为第二原发癌选择辅助治疗时应谨慎。
