| 1. |
- Kaaks, Rudolf, et al.
(author)
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Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status : A prospective study within the EPIC cohort
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:11, s. 2683-2690
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Journal article (peer-reviewed)abstract
- Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case–control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01–1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04–1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01–1.89]; OR = 1.19 [95% CI 1.04–1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER− breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER−/PR− disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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| 2. |
- Kaaks, Rudolf, et al.
(author)
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Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:8, s. 1947-1957
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Journal article (peer-reviewed)abstract
- Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1=1.56 (95% CI 1.15-2.13), p(trend)=0.02 for testosterone and ORQ4-Q1=1.33 (95% CI 0.99-1.79), p(trend)=0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1=1.32 (95% CI 0.87-2.01), p(trend)=0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1=0.94 (95% CI 0.60-1.47), p(trend)=0.34, p(het)=0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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| 3. |
- Kühn, Tilman, et al.
(author)
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Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition : A nested case-control study
- 2013
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:7, s. 1689-1700
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Journal article (peer-reviewed)abstract
- Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case-control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4-Q1 [95% CI]: 1.07 [0.85-1.36], ptrend = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4-Q1 [95% CI]: 0.97 [0.67-1.38], ptrend = 0.90) and estrogen receptor negative tumors (ORQ4-Q1 [95% CI]: 0.97 [0.66-1.42], ptrend = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80-1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) < 25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI ≥ 25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer.
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| 4. |
- Ritte, Rebecca, et al.
(author)
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Reproductive factors and risk of hormone receptor positive and negative breast cancer : a cohort study
- 2013
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In: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 13, s. Article Number: 584-
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Journal article (peer-reviewed)abstract
- Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR-(n = 998) and ER+PR+ (n = 3,567) breast tumors. Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR-tumors (= 35 vs. = 19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for ER+PR+ tumors; = 35 vs. = 19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96 for ER-PR-tumors; P-het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age-and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Conclusion: Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
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| 5. |
- Sieri, Sabina, et al.
(author)
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Dietary Fat Intake and Development of Specific Breast Cancer Subtypes.
- 2014
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:5, s. 068-068
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Journal article (peer-reviewed)abstract
- We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
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| 6. |
- Tikk, Kaja, et al.
(author)
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Prolactin Determinants in Healthy Women : A Large Cross-Sectional Study within the EPIC Cohort
- 2014
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:11, s. 2532-2542
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Journal article (peer-reviewed)abstract
- Background: Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear. Methods: We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort. Results: Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; P-cat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; P-cat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; P-cat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, >= 3 vs. 1 pregnancy, P-trend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers. Conclusions: Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women. Impact: Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.
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