Testosterone and Biological Characteristics of Breast Cancers in Postmenopausal Women

Secreto, Giorgio; Venturelli, Elisabetta; Meneghini, Elisabetta; Greco, Marco; Ferraris, Cristina; Gion, Massimo; Zancan, Matelda; Fabricio, Aline S C; Berrino, Franco; Cavalleri, A; Micheli, Andrea

doi:10.1158/1055-9965.epi-09-0540

Cited by 21 publications

(17 citation statements)

References 31 publications

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“…Notably, the subset of women who had the highest levels of T in both serum and adipose tissue included a preponderance of ER+/PR+ cancers. Thus, our findings provide additional evidence for the importance of T in post-menopausal ER+/PR+ breast cancer (27) and extend findings demonstrating etiological differences between hormone receptor positive and negative tumors.…”

Section: Discussionsupporting

confidence: 85%

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women

Falk

Gentzschein

Stanczyk

et al. 2011

Breast Cancer Res Treat

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Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. We used a previously validated method to measure levels of estrone, estradiol, androstenedione and testosterone in adipose tissue removed as part of breast excisions performed for cancer in 100 postmenopausal women (69 ER/PR +/+ and 31 ER/PR −/−) participating in a breast cancer case-control study. We also measured the same steroid hormones, as well as estrone sulfate, and SHBG in serum from these patients and 100 controls matched on ages at blood collection and on menopause. Overall, concentrations of serum hormones did not vary significantly between controls and cases. However, women with ER−/PR− breast cancers had lower circulating levels of all measured sex steroid hormones and higher SHBG levels than women with ER+/PR+ breast cancers and controls. Similarly, hormone concentrations in breast adipose tissue were higher among women with ER+/PR+ compared to ER−/PR− breast cancer, although differences were only significant for testosterone. These data demonstrate that high sex steroid concentrations in both serum and adipose tissues are more strongly related to ER+/PR+ than ER−/PR− breast cancers. Measurement of sex hormones in serum and in the microenvironment may help in understanding the hormonal etiology of breast cancer, suggest methods for prevention, and have value in gauging treatment response and prognosis.

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Section: Discussionsupporting

confidence: 85%

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women

Falk

Gentzschein

Stanczyk

et al. 2011

Breast Cancer Res Treat

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“…The association of serum testosterone with breast cancer has been reported to be stronger for estrogen receptor-positive versus -negative tumors [3,24,25], and one mechanism by which testosterone is hypothesized to increase breast cancer risk is through conversion to estradiol. Breast tissue estradiol is derived from direct uptake from the circulation and by local synthesis from precursors, such as testosterone [26].…”

Section: Discussionmentioning

confidence: 99%

Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk

et al. 2010

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IntroductionBreast cancer is frequently a hormonally dependent cancer, and associations of circulating estrogens and androgens with subsequent breast cancer risk are well established in postmenopausal women. Associations of serum estrogens and androgens with breast cancer risk in premenopausal women are less well studied. The objective of this study was to determine whether estradiol and testosterone levels in serum collected before menopause are associated with subsequent breast cancer risk.MethodsWe conducted a prospective case-control study of 266 participants who were registered in the Columbia, Missouri, Serum Bank and not using exogenous hormones at the time of blood collection. Each of 98 in situ or invasive breast cancer cases with prediagnostic serum collected before menopause was matched to two controls by age, date, menstrual cycle day, and time of day of blood collection. Estradiol and testosterone concentrations were quantified by using specific radioimmunoassays, and sex hormone-binding globulin (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of the non-SHBG bound hormone fractions. Data were analyzed by using conditional logistic regression. All tests of statistical significance were two-sided.ResultsSerum testosterone was strongly and significantly associated with breast cancer risk. The relative odds (OR) for increasing quartiles of total testosterone were 1.0, 2.1 (95% confidence interval (CI) 0.9 to 4.8), 1.5 (95% CI, 0.6 to 3.4), and 3.3 (95% CI, 1.5 to 7.5, Ptrend = 0.006). Comparable ORs for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0, 1.7 (95% CI, 0.7 to 4.2), 1.7 (95% CI, 0.7 to 4.0), and 4.2 (95% CI, 1.6 to 10.9, Ptrend = 0.002). Total and non-SHBG-bound estradiol were not associated with breast cancer, but extreme variation in levels across the menstrual cycle coupled with relatively small numbers, particularly for analyses stratified by cycle phase, limited the power to detect associations.ConclusionsResults suggest that premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer.

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“…Inclusion and exclusion criteria of the TPM cohort were extensively presented elsewhere [13,14] and are here briefly summarized: all patients with primary breast cancer were treated surgically at the Breast Surgery Unit of the Fondazione IRCSS Istituto Nazionale Tumori, Milan (INT) from December 2003 to December 2006. Inclusion criterium was having histologically confirmed non-metastatic breast carcinoma (any T, any N, M0); exclusion criteria were nonepithelial cancer, a previous cancer diagnosis (except in situ cervical cancer or nonmelanoma skin cancer), and neoadjuvant chemotherapy or hormone therapy.…”

Section: Methodsmentioning

confidence: 99%

“…We recently examined the relationships of serum testosterone levels with some tumor characteristics in a cohort of postmenopausal breast cancer patients and found that high levels of testosterone were significantly associated with the ER-positive status of tumors [13,14], a finding suggesting that serum testosterone levels are a marker of hormone-dependent breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers

et al. 2012

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BackgroundAndrogen receptors (AR) are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development.MethodsAR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics. AR expression was classified according to the percentage of stained cells: AR-absent (0%) and AR-poorly (1%-30%), AR-moderately (>30%-60%), and AR-highly (>60%) positive.ResultsStatistical analysis was performed in 451 patients who experienced natural menopause. AR-high expression was significantly related with low histologic grade and estrogen receptor (ER)- and progesterone receptor (PR)-positive status (P trend<0.001). Mean testosterone levels were significantly higher in the AR-high category than in the other categories combined (P=0.022), although a trend across the AR expression categories was not present. When women defined by ER status were analyzed separately, regression analysis in the ER-positive group showed a significant association of high testosterone levels with AR-highly-positive expression (OR 1.86; 95% CI, 1.10-3.16), but the association was essentially due to patients greater than or equal to 65 years (OR 2.42; 95% CI, 1.22-4.82). In ER-positive group, elevated testosterone levels appeared also associated with AR-absent expression, although the small number of patients in this category limited the appearance of significant effects (OR 1.92; 95% CI, 0.73–5.02): the association was present in both age groups (<65 and ≥65 years). In the ER-negative group, elevated testosterone levels were found associated (borderline significance) with AR-absent expression (OR 2.82, 95% CI, 0.98-8.06). In this ER-negative/AR-absent subset of tumors, elevated testosterone levels cannot stimulate cancer growth either directly or after conversion into estrogens, but they probably induce increased synthesis of some other substance that is responsible for cancer growth through binding to its specific receptor.ConclusionsThe findings in the present study confirm that testosterone levels are a marker of hormone-dependent breast cancer and suggest that the contemporary evaluation of ER status, AR expression, and circulating testosterone levels may identify different subsets of cancers whose growth may be influenced by androgens.

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Testosterone and Biological Characteristics of Breast Cancers in Postmenopausal Women

Cited by 21 publications

References 31 publications

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women

Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk

Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers

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