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绝经后乳腺癌女性中肥胖及身体活动与血清和肿瘤内性甾体激素水平的关联:配对血清和肿瘤组织样本分析

Associations of obesity and physical activity with serum and intratumoral sex steroid hormone levels among postmenopausal women with breast cancer: analysis of paired serum and tumor tissue samples.

作者信息

Kakugawa Yoichiro, Tada Hiroshi, Kawai Masaaki, Suzuki Takashi, Nishino Yoshikazu, Kanemura Seiki, Ishida Takanori, Ohuchi Noriaki, Minami Yuko

机构信息

Department of Breast Oncology, Miyagi Cancer Center Hospital, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi, 981-1239, Japan.

Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

出版信息

Breast Cancer Res Treat. 2017 Feb;162(1):115-125. doi: 10.1007/s10549-016-4094-3. Epub 2017 Jan 2.

Abstract

PURPOSE

It has been hypothesized that intratumoral estrogens may play important roles in the growth of breast cancer. However, few studies have investigated such intratumoral hormones, or their association with risk factors of breast cancer.

METHODS

In this cross-sectional study, hormone levels in paired serum and tumor tissue samples from 146 postmenopausal women with breast cancer were measured by liquid chromatography-tandem mass spectrometry and compared between estrogen/progesterone (ER/PgR) subtypes. The associations of risk factors including body mass index (BMI) and other lifestyle factors with these hormone levels were investigated using analysis of covariance.

RESULTS

The level of estradiol (E2) in tumor tissue was extremely high in women with ER+ (geometric mean 95.6 pg/g) relative to women with ER-/PgR- (8.9 pg/g), whereas serum E2 level did not differ much between the two groups (3.1 and 2.8 pg/ml, respectively). Serum levels of precursors for E2, including testosterone (T) and androstenedione (Adione), and tissue Adione level, were high among women with ER+. After adjustment for confounding variables, BMI was found to be positively associated with tissue levels of E2, estrone (E1), T, and Adione among women with ER+ (P  < 0.0001 for E2; 0.0016 for E1; 0.0002 for T; and 0.03 for Adione).

CONCLUSION

The data suggest that tissue E2 is related to the growth of receptor-positive breast cancer and that risk factors such as BMI affect tissue levels of E2 and its precursors. Understanding of hormonal environments within tumor tissue may be important for elucidating hormonal etiology of breast cancer and improving the prognosis of patients.

摘要

目的

有假说认为肿瘤内雌激素可能在乳腺癌生长中起重要作用。然而,很少有研究调查此类肿瘤内激素,或其与乳腺癌危险因素的关联。

方法

在这项横断面研究中,采用液相色谱 - 串联质谱法测量了146名绝经后乳腺癌女性配对的血清和肿瘤组织样本中的激素水平,并在雌激素/孕激素(ER/PgR)亚型之间进行比较。使用协方差分析研究包括体重指数(BMI)和其他生活方式因素在内的危险因素与这些激素水平的关联。

结果

相对于ER - /PgR - 的女性(8.9 pg/g),ER + 的女性肿瘤组织中雌二醇(E2)水平极高(几何平均数95.6 pg/g),而两组之间血清E2水平差异不大(分别为3.1和2.8 pg/ml)。ER + 的女性中,E2的前体血清水平,包括睾酮(T)和雄烯二酮(Adione),以及组织Adione水平较高。在对混杂变量进行调整后,发现BMI与ER + 的女性中E2、雌酮(E1)、T和Adione的组织水平呈正相关(E2为P < 0.0001;E1为0.

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