Study to determine whether SNPs in CYP17A1, ESR1, and TNRC9 loci correlate with increased breast cancer risk and serum 25-OH vitamin D levels.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13086-e13086 ◽  
Author(s):  
Nobuyasu Yoshimoto ◽  
Yu Dong ◽  
Hiroshi Sugiura ◽  
Mitsuo Terada ◽  
Naoto Kondo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Premenopausal Women ◽  
Individual Snps ◽  
Significant Difference ◽  
25 Oh Vitamin D

e13086 Background: Low serum 25-OH vitamin D (25-OH Vit.D) level is associated with a higher risk of breast cancer. Many single nucleotide polymorphisms (SNP) are associated with breast cancer risk, although the mechanisms underlying this association in most cases remain unclear. We attempted to address this issue by determining whether specific SNPs were correlated with breast cancer-associated biomarkers (BM). Methods: We analyzed estrogen receptor (ER)-positive breast cancer patients treated between Jan 2011 and Dec 2014. We measured serum testosterone and 25-OH Vit.D in pre- and post-menopausal women, and also measured estradiol in the latter group. We genotyped 7 individual SNPs both in premenopausal and postmenopausal women. We then looked for correlations between BMs and SNPs in all three genotypes (homozygotes of major alleles, heterozygotes and homozygotes of minor alleles) using the Kruskal-Wallis test. For each SNP locus associated with a trend or significant effect with regard to BM levels, a t-test was then applied to determine which of the two genotypes was responsible for the effect. Results: Four hundred thirteen women were enrolled (163 premenopausal patients, and 250 postmenopausal patients). There was a trend difference between CYP17A1 rs743572 and 25-OH Vit.D (p = 0.0888), ESR1 rs204210 and 25-OH Vit.D (p = 0.0534) in premenopausal women, and a significant difference between TNRC9 rs3803662 and 25-OH Vit.D (p = 0.026) in postmenopausal women. Among premenopausal women, 25-OH Vit.D levels were significantly lower in those with the high-risk rs743572 genotype TC when compared with TT individuals (19.2 +/- 6.7 ng/ml vs 22.9 +/- 8.7 ng/ml; p = 0.0125). Similarly, 25-OH Vit.D was significantly lower in women with the high-risk rs204210 genotype AG when compared with GG individuals (19.1 +/- 6.9 ng/ml vs 21.7 +/- 6.4 ng/ml; p = 0.0219). In postmenopausal women, 25-OH Vit.D was significantly lower in women with the high-risk rs3803662 genotype GG than those with the AA genotype (20.5 +/- 9.2 ng/ml vs 24.4 +/- 8.0 ng/ml; p = 0.0104). Conclusions: Specific SNPs in CYP17A1, ESR1, and TNRC9 genes may modulate breast cancer risk due to their influence on serum 25-OH Vit.D levels.

The Women’s Health Initiative randomized trial of calcium plus vitamin D: Effects on breast cancer and arthralgias

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA6-LBA6 ◽  
Author(s):  
R. T. Chlebowski ◽  
K. C. Johnson ◽  
C. Kooperberg ◽  
A. Hubbell ◽  
D. Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Breast Cancer Incidence ◽  
Secondary Outcome ◽  
Baseline Serum ◽  
Abnormal Mammogram ◽  
Joint Symptoms

LBA6 Background: Calcium (Ca) and vitamin D (D) have been associated with reduced breast cancer and breast density in observational studies. Randomized trials have not evaluated Ca/D supplementation for breast cancer prevention. Methods: We randomized 36,282 postmenopausal women without prior breast cancer from 40 WHI centers to 1000 mg of elemental calcium as calcium carbonate and 400 IU of vitamin D3 (N = 18,176) daily or matching placebo (N = 18,106); 54% were also randomized one year previously to hormone therapy (HT) or placebo; conjugated equine estrogen (CEE) plus medroxyprogesterone acetate or CEE alone (the latter for those with prior hysterectomy). Ca/D effects on hip fracture and colorectal cancer have been reported (NEJM 2006). We report here pathologically confirmed invasive breast cancer as a secondary outcome of the Ca/D trial. Baseline serum 25(OH) D levels (in 1787 women) and serial joint symptoms (pain/stiffness and hand/feet swelling 0–3 scale, in a 6% sample) were also assessed. Results: Breast cancer incidence did not differ between Ca/D and placebo randomization groups (528 and 546 cases in Ca/D and placebo; hazard ratio 0.96; 95 percent confidence interval (CI), 0.85, 1.09). While SEER stage and abnormal mammogram frequency were similar between groups, breast cancers were smaller in the Ca/D group (1.54 cm (1.23), mean (SD) versus 1.71 (1.29), P = 0.05). Total vitamin D baseline intake was associated with lower breast cancer risk in the placebo group. Baseline vitamin D (nmol per liter) deficiency was common (≥30, sufficient (n = 266), 16 ≤ 30, insufficient (277), < 16, deficient (743)) but was not related to joint pain (seen in 72.2%, 74.0%, 74.6%, of sufficiency and deficiency groups, respectively). Joint symptoms were lower in women randomized to CEE alone (P < 0.01) but did not significantly differ by Ca/D group assignment and no significant interactions were seen between HT and Ca/D. Conclusion: Among healthy postmenopausal women, Ca/D supplementation did not reduce breast cancer risk but the cancers in those randomized to Ca/D were somewhat smaller. Exogenous estrogen use but not Ca/D supplementation influences arthralgias. [Table: see text]

Association of baseline plasma levels of 25OH vitamin D and breast cancer risk in a chemoprevention trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1546-1546
Author(s):  
Bernardo Bonanni ◽  
Davide Serrano ◽  
Sara Gandini ◽  
Harriet Ann Johansson ◽  
Debora Macis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Vitamin D ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Premenopausal Women ◽  
Plasma Vitamin ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
Chemoprevention Trial

1546 Background: Observational studies have shown a correlation of higher serum 25-hydroxyvitamin D (25OHD) concentrations and reduced cancer risk, including breast cancer (BC). We assessed the association of 25OHD and Vitamin D Receptor (VDR) polymorphisms (SNPs) with breast cancer events within a chemoprevention trial in premenopausal women at risk for BC. Methods: Premenopausal women with history of intraepithelial neoplasia (IEN) or at risk women according to the Gail model were included in a 4 arm phase II prevention trial (low dose tamoxifen vs fenrerinide vs their combination vs placebo). Level of 25OHD were measured at baseline. VDR SNPs ( FokI, BsmI, TaqI, ApaI, and Cdx2) were determined using the Applied Biosystems’ Taqman Allelic Discrimination Assay according to manufacturer’s instructions. Survival analysis for breast cancer events was performed using competing risk models, adjusted for BMI, age, season and risk strata. Results: Plasma samples were available for 228 subjects. At baseline the median plasma 25OHD concentrations were slightly higher in 53 unaffected women, 19.6 ng/ml (IQR 12.7-27.3 ng/mL) than in 175 women with IEN, 18.8 ng/ml (11.7-25.8). After a median follow up of 15 years, 79 women developed a breast cancer event, 12 had different neoplastic events. The median level of 25OHD was 19.7 ng/ml (IQR 12.8-26.1) in subjects free from oncological events and 17.8 ng/ml (9.7-23.9) in subjects with breast events. Women in the lowest 25OHD quartile (≤12 ng/ml) had an increased risk of breast cancer events: HR = 1.79 (95%CI, 1.07-2.99, p = 0.03). Considering all cancer events, the associations with 25OHD were confirmed (P = 0.005). Among the VDR SNPs the ApaI variant in homozygote or heterozygote versus wild type showed an HR of 1.83 (95%CI, 1.04-3.21 p = 0.03). Conclusions: Our results support a role of plasma vitamin D levels in breast cancer risk. Subjects in the lowest quartile had a two-fold increased risk of a cancer event. Our findings support trials of 25OHD supplementation to prevent breast cancer in 25OHD insufficient subjects.

scholarly journals Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update

2019 ◽  
Vol 37 (33) ◽  
pp. 3152-3165 ◽  
Author(s):  
Kala Visvanathan ◽  
Carol J. Fabian ◽  
Elissa Bantug ◽  
Abenaa M. Brewster ◽  
Nancy E. Davidson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Risk Reduction ◽  
Endocrine Therapy ◽  
Premenopausal Women ◽  
Increased Risk ◽  
Breast Cancer Risk Reduction ◽  
Cancer Risk Reduction

PURPOSE To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor–positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines .

scholarly journals Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer

2011 ◽  
Vol 111 (6) ◽  
pp. 1687-1693 ◽  
Author(s):  
D. A. Kossman ◽  
N. I. Williams ◽  
S. M. Domchek ◽  
M. S. Kurzer ◽  
J. E. Stopfer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Menstrual Cycle ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Luteal Phase ◽  
Premenopausal Women ◽  
High Risk Women ◽  
Estrogen Exposure ◽  
Hormone Exposure

Experimental and clinical data support a role for estrogens in the development and growth of breast cancer, and lowered estrogen exposure reduces breast cancer recurrence and new diagnoses in high-risk women. There is varied evidence that increased physical activity is associated with breast cancer risk reduction in both pre- and postmenopausal women, perhaps via lowered estrogen levels. The purpose of this study was to assess whether exercise intervention in premenopausal women at increased breast cancer risk reduces estrogen or progesterone levels. Seven healthy premenopausal women at high risk for breast cancer completed a seven-menstrual-cycle study. The study began with two preintervention cycles of baseline measurement of hormone levels via daily first-morning urine collection, allowing calculation of average area under the curve (AUC) hormone exposure across the menstrual cycle. Participants then began five cycles of exercise training to a maintenance level of 300 min per week at 80–85% of maximal aerobic capacity. During the last two exercise cycles, urinary estradiol and progesterone levels were again measured daily. Total estrogen exposure declined by 18.9% and total progesterone exposure by 23.7%. The declines were mostly due to decreased luteal phase levels, although menstrual cycle and luteal phase lengths were unchanged. The study demonstrated the feasibility of daily urine samples and AUC measurement to assess hormone exposure in experimental studies of the impact of interventions on ovarian hormones. The results suggest value in exercise interventions to reduce hormone levels in high-risk women with few side effects and the potential for incremental benefits to surgical or pharmacologic interventions.

scholarly journals Vitamin D and calcium intakes and breast cancer risk in pre- and postmenopausal women

2010 ◽  
Vol 91 (6) ◽  
pp. 1699-1707 ◽  
Author(s):  
Laura N Anderson ◽  
Michelle Cotterchio ◽  
Reinhold Vieth ◽  
Julia A Knight
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women

Mammographic Density, Response to Hormones, and Breast Cancer Risk

2011 ◽  
Vol 29 (22) ◽  
pp. 2985-2992 ◽  
Author(s):  
Norman F. Boyd ◽  
Olga Melnichouk ◽  
Lisa J. Martin ◽  
Greg Hislop ◽  
Anna M. Chiarelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Mammographic Density ◽  
Premenopausal Women ◽  
Case Control Studies ◽  
Dense Area ◽  
Hormone Exposure ◽  
The Difference

Background Percent mammographic density (PMD) is a strong risk factor for breast cancer that changes in response to changes in hormone exposure. We have examined the magnitude of the association of hormone exposure with PMD according to subsequent breast cancer risk. Methods In three case-control studies, with 1,164 patient cases and 1,155 controls nested in cohorts of women screened with mammography, we examined the association of PMD measured in the baseline mammogram with risk of breast cancer in the following 1 to 8 years (mean, 3 years), according to use of oral contraceptives (OCs) in premenopausal women, menopause, and hormone therapy (HT) in postmenopausal women. All statistical comparisons are adjusted for age and other risk factors. Results In premenopausal women who later developed breast cancer (patient cases), PMD was 5.3% greater in past users of OCs than in nonusers (P = .06). In controls, OC users had 2% less density than nonusers (P = .44; test for interaction P = .06). The difference in PMD between premenopausal and postmenopausal women for patient cases was 8.5% (P < .001) and for controls, 3.9% (P = .01; test for interaction P = .03). In postmenopausal women, PMD was 6% greater in patients who used HT than in never users (P < .001). Controls who used HT had 1.6% greater PMD (P = .26) than never users (test for interaction P = .001). Differences in PMD resulted mainly from differences in the dense area of the mammogram. Conclusion Differences in PMD associated with differences in hormone exposure were greater in women who later developed breast cancer than in controls in each of the hormone exposures examined.

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