For Physicians

PHYSICIAN TESTING

See Your Physician for Urine, Blood or Saliva Testing that specifically examines estrogen metabolism:

Genetic Tests specifically for Estrogen Metabolism are available from:
Genosense www.Genosense.com (The Estrogen Gene Test Company, www.estrogengenetest.com partners with Genosense) and
Genova Diagnostics www.gdx.net

Blood Test available from Quest, Labcorp and Specialty Labs
2-Hydroxyestrone
16 Alpha-Hydroxyestrone
2:16 Alpha-Hydroxyestrone

*Note: Point-in-Time estrogen testing is notoriously unstable especially for pre-menopausal women. I strongly recommend the genetic test as menstrual life stage does not affect results.
Estrogen metabolism testing has no bearing whatsoever on breast cancer risk.

EGT Introduction

It is now well-documented that a woman’s cumulative exposure to estrogen throughout her life is associated with her risk of breast cancer. Developed countries have and will continue to use estrogen medications such as oral contraception, hormone replacement therapy (HRT), bio-identical supplementation and medications to enhance fertility. Especially concerning is the current trend of an increasing incidence of estrogen receptor-positive breast cancers, with epidemiologists from the National Cancer Institute projecting a rise from 158 to 166 cases per 100,000 women in the U.S. by the year 2016.

Many scientists have drawn attention to what is known as the dual carcinogenetic mechanism of estrogen. In addition to fueling estrogen receptor-positive breast cancers, estrogens enhance cell proliferation and acts as genotoxic precursors. Efforts have mapped single nucleotide polymorphisms (SNPs) in several estrogen metabolism genes that confer an increased risk of breast cancer. Breakthrough studies from Vanderbilt University, the University of Alberta, Harvard, and others, have found significant, synergistic interactions between specific groups of estrogen metabolism SNPs in association with breast cancer. These groups of SNPs simulate well-defined carcinogenetic mechanisms within the estrogen metabolism pathway.

Download EGT White Paper »

Importantly, these SNPs are not included in the traditional handful of familial breast cancer susceptibility genes such as BRCA1 and BRCA2. Familial genes account for less than 20% of breast cancers. The SNPs of interest occur in six estrogen metabolism genes. Interestingly, one SNP is not sufficient to increase the risk of breast cancer, but the interaction of two or more SNPs can increase breast cancer risk from 2.5 to as much as 13 fold.

The Estrogen Gene Test is a simple saliva test that can be used to identify polymorphisms in all of the key estrogen metabolism genes. It is a unique tool that can identify patients who inappropriately metabolize estrogen and related compounds. While every woman should have an Estrogen Gene Test performed at some point, the test is particularly important in women who are considering oral contraceptives, hormone replacement therapy, bio-identical supplementation, in vitro fertilization, or who have been diagnosed with estrogen receptor-positive breast cancer. With this knowledge in hand, clinicians can mitigate breast cancer risk through targeted nutritional and lifestyle interventions.

Recent Peer-Studied Reviews

 

The New England Journal of Medicine review article “Estrogen Carcinogenesis in Breast Cancer”

In this article, they review recent findings related to estrogen exposure and the risk of breast cancer, the mechanisms that may be involved, and the clinical implications of these findings.  Download pdf »


June 2011 University of Ljubljana Study in Journal of Gynecologic Oncology

Clearly written study with 825 cases and 732 controls in study. Results indicate women with snps on 2 estrogen metabolism genes face 2 fold risk of breast cancer. Women with snps on 3 estrogen metabolism.  Download pdf »


May 2011 Study American Association of Cancer Research from Vanderbilt University, Fischer-Bosch Institute Stutgart and University Tubingen

Large Study with 1143 Breast cancer patients and 1155 controls with further examination of the Nashville Breast Cohort study of 16,946 women. Results indicate 1.88 fold increase of breast cancer risk. Download pdf »


Vanderbilt University, Nashville, TN, 2009 NY Academy of Sciences Estrogen Metabolism and Breast Cancer: A Risk Model

Steroid Enzymes and Cancer: 2009 New York Academy of Sciences Comment from Babs: If you can only read one item, read this study. More Studies on Estrogen Metabolism SNPs and Breast Cancer. Download pdf »


Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK, June 2012 Journal of the National Cancer Institute

CYP3A variation, Premenopausal Estrone Levels and Breast Cancer Risk Download pdf »

Fertility Curve Shifts Down 5 Years

 

University of St. Andrews and University of Edinburgh, Scotland, U.K. Human Ovarian Reserve from Conception to Menopause – 2010

This study demonstrates that for 95% of women by the age of 30 only 12% of their ovarian reserves remain. By age 40, 3% remains. Download pdf »


Danish Cancer Society, Institute of Cancer Epidemology & Juliane Marie Center, Copenhagen, Denmark — Breast Cancer Risk after Fertility Drugs Exposure

Cancer Epidemiology, Biomarkers and Prevention July 2007 16: 1400 Download pdf »


John Hopkins, Bloomberg School of Public Health, Washington, D.C. Cancer Risk after Ovulation Induction

American Journal of Epidemiology, Vol. 169, No 3 November 2008 “In conclusion, the present study demonstrated an association between treatment for ovulation induction and overal risk of cancer, partic Download pdf »

Hormone Replacement Therapy and Breast Cancer Studies

 

NSERM, IARG WHO, Univerity of Paris Sud —- Breast Cancer Risk & Hormone Replacement Therapy

International Union Against Cancer, 2004 Download pdf »


INSERM, University of Paris & Instituto Nazionale Tumori, Milan — Different Postmenopausal Hormone Therapies & Risk of Breast Cancer

Journal of Clinical Oncology, March 2008 Download pdf »

Studies on Estrogen Metabolism SNPs and Breast Cancer

 

University of Nebraska Medical Center, Eppley Institute, Nashville, TN, Center for Human Genetics — Depurinating estrogen-DNA adducts in the etiology and prevention of breast and human cancer

Future Oncology, 2010 Download pdf »


Vanderbilt University, Nashville, TN, Center for Human Genetics — Estrogen, Enzyme Variants and Breast Cancer Risk Model

Cancer Epidemiol Biomarkers Prev 2006;15(9). “….The model identified a subset of women with an increased risk of breast cancer based on their enzyme halotype and consequent E2-3, 4-Q production.” Download pdf »


University of Nebraska Medical Center, Eppley Institute, Nashville TN, Center for Human Genetics — Relative Imbalances in Estrogen Metabolism and conjugation in breast tissue…biomarkers

Carcinogenesis, 2003 Download pdf »


Vanderbilt University, Nashville, TN — Multifactor-Dimensionality Reduction Reveals High Order Interactions among….

“Estrogen Metabolism Genes in Sporadic Breast Cancer” American Society of Human Genetics, 2001. Babs comment: “This is first study on human tissue correlating these SNPs and Breast Cancer.” Download pdf »


Ningxia Medcal, Yinchuan, Ningxia, P.R. China & Lancaster University, Lancaster, UK — CYP1B1 Polymorphisms and Breast Cancer

Biomarkers Insight 2010:5 “Our results suggest that certain polymorphisms in the CYP1B1 gene might increase risk for breast cancer among Han Chinese, perhaps because they influence the efficiency of C Download pdf »


University of Nebraska, Eppley Institue for Cancer Research — Breast Cancer and Estrogen Metabolism: Catechol estrogen quinones as initiators of breast cancer

Biochim Biophys Acta 2006 Aug:1766 “In summary, this evidence strongly indicates that estrogens can become endogenous tumor initiators when CE3-3, 4-Q react with DNA to form specific depurinating addu  Download pdf »


Harvard School of Public Health & Brigham Women’s Hospital & Harvard Medical School —-CYP1B1 SNPs and Breast Cancer Risk

Cancer Epidemiology, Biomarkers and Prevention, Vol 11, May 2002 “Our results suggest that despite a potential association with estradiol levels, neither the V432L nor the A453S polymorphisms in the C  Download pdf »


CYP1B1 and COMT SNPS and Breast Cancer in Turkish Women

Archives of Toxicology Vol 76, Num 11/November 2002 “We conclude that the CYP1B1*3 allele appears to be a factor for susceptability to breast cancer in Turkish women…”  Download pdf »


National Taiwan University, Taipei, Taiwan Breast Cancer Risk and SNPs CYP17, CYP1A1 and COMT

Cancer Research 59, October 1999.  Download pdf »

Estrogen Metabolism & Breast Cancer Risk

An impaired estrogen metabolism (SNPs on the Genes CYP1B1, CYP1A1, COMT, GSTM or GSTP1) + exogenous estrogens (fertility treatments, long term HRT) will lead to an over expression of the carciogenic estrogens.