Endogenous Estrogen, Androgen, and Progesterone Concentrations and Breast Cancer Risk Among Postmenopausal Women
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.
- SourceAvailable from: Christina L Addison
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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     . 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)  "
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. "
ABSTRACT: Background: High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. Material and Methods: Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. Results: The study revealed the details of physiological characteristics of female breast cancer. Mean age was 37.72∓5.99 and 55.05∓7.28 years and serum CA 15-3 (MUC1) level was 60.47∓8.59 and 63.17∓4.58 U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. Conclusion: There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.Asian Pacific journal of cancer prevention: APJCP 10/2012; 13(10):5257-61. DOI:10.7314/APJCP.2012.13.10.5257 · 2.51 Impact Factor
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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). "
ABSTRACT: Background:We aimed to assess whether 2D : 4D measures are associated with breast cancer risk.Methods:We derived the ratio of the lengths of the index and ring fingers (2D : 4D), and right minus left 2D : 4D (Δ(r-l)) from digit lengths measured from photocopies of participants' hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. Of the 9044 women with available data, we identified 573 incident breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D : 4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D : 4D measures and age at menarche and menopause.Results:We found a direct association between left 2D : 4D and breast cancer risk, an inverse association between Δ(r-l) and risk of breast cancer, but no association between right 2D : 4D and breast cancer risk. Among breast cancer cases, both right 2D : 4D and Δ(r-l) were inversely associated with age at diagnosis. We also observed associations between both right 2D : 4D and Δ(r-l) and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause.Conclusion:Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer.British Journal of Cancer 09/2012; 107(9):1631-6. DOI:10.1038/bjc.2012.418 · 4.82 Impact Factor