Endogenous Estrogen, Androgen, and Progesterone Concentrations and Breast Cancer Risk Among Postmenopausal Women

Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 01/2005; 96(24):1856-65. DOI: 10.1093/jnci/djh336
Source: PubMed

ABSTRACT Levels of endogenous hormones have been associated with the risk of breast cancer among postmenopausal women. Little research, however, has investigated the association between hormone levels and tumor receptor status or invasive versus in situ tumor status. Nor has the relation between breast cancer risk and postmenopausal progesterone levels been investigated. We prospectively investigated these relations in a case-control study nested within the Nurses' Health Study.
Blood samples were prospectively collected during 1989 and 1990. Among eligible postmenopausal women, 322 cases of breast cancer (264 invasive, 41 in situ, 153 estrogen receptor [ER]-positive and progesterone receptor [PR]-positive [ER+/PR+], and 39 ER-negative and PR-negative [ER-/PR-] disease) were reported through June 30, 1998. For each case subject, two control subjects (n = 643) were matched on age and blood collection (by month and time of day). Endogenous hormone levels were measured in blood plasma. We used conditional and unconditional logistic regression analyses to assess associations and to control for established breast cancer risk factors.
We observed a statistically significant direct association between breast cancer risk and the level of both estrogens and androgens, but we did not find any (by year) statistically significant associations between this risk and the level of progesterone or sex hormone binding globulin. When we restricted the analysis to case subjects with ER+/PR+ tumors and compared the highest with the lowest fourths of plasma hormone concentration, we observed an increased risk of breast cancer associated with estradiol (relative risk [RR] = 3.3, 95% confidence interval [CI] = 2.0 to 5.4), testosterone (RR = 2.0, 95% CI = 1.2 to 3.4), androstenedione (RR = 2.5, 95% CI = 1.4 to 4.3), and dehydroepiandrosterone sulfate (RR = 2.3, 95% CI = 1.3 to 4.1). In addition, all hormones tended to be associated most strongly with in situ disease.
Circulating levels of sex steroid hormones may be most strongly associated with risk of ER+/PR+ breast tumors.

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    • "In addition, several studies note that higher serum levels of estrogen in postmenopausal women are associated with increased breast cancer risk [19] [20] [21] [22] [23]. A meta-analysis of nine prospective studies, with data on 2428 predominantly postmenopausal women, 663 with breast cancer, demonstrated a roughly twofold higher risk of breast cancer in women with higher serum estrogen (2nd–4th quartiles) compared to those with lower levels (1st quartile) [24] "
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    ABSTRACT: Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a “low estrogen environment”, either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest.
    12/2013; 2(4). DOI:10.1016/j.jbo.2013.06.001
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    • "The present study found that these receptors (PR, ER, and HER-2/neu) were positive in 50% patients amongst premenopausal women, while 65% of menopausal women's cancer was associated ER, PR positive and Her-2/neu negative and remaining 35% were triple negative (ER, PR and HER2/neu -ve). Our results were in accordance with another study that found a significant association between HER-2/neu receptor positivity and tumour size and negative ER/PR status (Missmer et al., 2004). Present study observed a significant increased level of CA 15-3 in both group of pre and post menopausal women as compared to normal subjects. "
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    • "There is substantial evidence implicating androgens and oestrogens in the aetiology of breast cancer. Prospective studies have consistently reported that higher levels of endogenous oestrogens and androgens, and lower levels of sex hormone binding globulin (SHBG) are associated with risk of post-menopausal breast cancer (Key et al, 2002; Manjer et al, 2003; Missmer et al, 2004; Zeleniuch- Jacquotte et al, 2004; Kaaks et al, 2005b; Hankinson and Eliassen, 2007; Baglietto et al, 2010), and there is some evidence indicating similar associations with pre-menopausal breast cancer risk as well (Kaaks et al, 2005a; Eliassen et al, 2006). Additionally, many wellestablished risk factors for breast cancer such as age at menarche, age at menopause, hormone replacement therapy use, and duration of lactation can be considered measures of cumulative exposure to oestrogen that the breast epithelium is exposed to over time (Henderson and Feigelson, 2000). "
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