Skip to main content

Advertisement

SpringerLink
Log in

Baseline E2 levels are higher in BRCA2 mutation carriers: a potential target for prevention?

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

BRCA gene mutations and elevated serum estradiol (E2) are well-known risk factors for breast cancer. The aim of this study was to investigate the association between BRCA gene mutations and serum E2 level.

Methods

We measured baseline (menstrual cycle day 2–3) E2 levels of 96 women with breast cancer who underwent BRCA testing.

Results

The mean age, parity, and age at menarche did not differ between women with and without BRCA1/2 mutations. Basal serum E2 level was significantly higher in women with BRCA2 mutations compared to women with BRCA1 mutations or without BRCA mutations (71.7 ± 41.6 vs. 45.5 ± 20.7 vs. 38.5 ± 12.6 pg/ml in BRCA2 mutation carriers, BRCA1 mutation carriers, and non-carriers, respectively, p value = 0.03). Women with BRCA2 mutations had 3.1 times as great risk for high basal E2 level (>48 pg/ml) as women without BRCA mutations after adjusting for age and BMI (95 % confidence interval: 1.3, 7.6). BRCA mutation carriers with high serum E2 level were significantly younger than the carriers with low serum E2 level (31.4 ± 3.1 vs. 34.7 ± 4.9 years, p = 0.04).

Conclusions

In this pilot study, we found an association between high basal serum E2 levels and BRCA2 mutations. Our results suggest that increased production of E2 may have a role in the pathogenesis of BRCA2-mutation-related breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6(6):229–239

    Article  PubMed  Google Scholar 

  2. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130

    Article  PubMed  CAS  Google Scholar 

  3. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet 62(3):676–689

    Article  PubMed  CAS  Google Scholar 

  4. Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (1999) Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science 285(5428):747–750

    Article  PubMed  CAS  Google Scholar 

  5. Oktay K, Kim JY, Barad D, Babayev SN (2010) Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol 28(2):240–244

    Article  PubMed  CAS  Google Scholar 

  6. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR et al (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346(21):1609–1615

    Article  PubMed  Google Scholar 

  7. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E et al (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346(21):1616–1622

    Article  PubMed  Google Scholar 

  8. Rebbeck TR, Levin AM, Eisen A, Snyder C, Watson P, Cannon-Albright L, Isaacs C, Olopade O, Garber JE, Godwin AK et al (1999) Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 91(17):1475–1479

    Article  PubMed  CAS  Google Scholar 

  9. Fisher B (1999) Highlights from recent National Surgical Adjuvant Breast and bowel project studies in the treatment and prevention of breast cancer. CA Cancer J Clin 49(3):159–177

    Article  PubMed  CAS  Google Scholar 

  10. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J, Ford L, Dunn BK, Costantino J et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286(18):2251–2256

    Article  PubMed  CAS  Google Scholar 

  11. Seery LT, Knowlden JM, Gee JM, Robertson JF, Kenny FS, Ellis IO, Nicholson RI (1999) BRCA1 expression levels predict distant metastasis of sporadic breast cancers. Int J Cancer 84(3):258–262

    Article  PubMed  CAS  Google Scholar 

  12. Hu Y, Ghosh S, Amleh A, Yue W, Lu Y, Katz A, Li R (2005) Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression. Oncogene 24(56):8343–8348

    Article  PubMed  CAS  Google Scholar 

  13. Malone JL, Nelson AC, Lieberman R, Anderson S, Holt JT (2009) Oestrogen-mediated phosphorylation and stabilization of BRCA2 protein in breast. J Pathol 217(3):380–388

    Article  PubMed  CAS  Google Scholar 

  14. Lee S, Ozkavukcu S, Heytens E, Moy F, Alappat RM, Oktay K (2011) Anti-Mullerian hormone and antral follicle count as predictors for embryo/oocyte cryopreservation cycle outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone. J Assist Reprod Genet 28(7):651–656

    Article  PubMed  Google Scholar 

  15. Stovall DW, Toma SK, Hammond MG, Talbert LM (1991) The effect of age on female fecundity. Obstet Gynecol 77(1):33–36

    PubMed  CAS  Google Scholar 

  16. Eliassen AH, Missmer SA, Tworoger SS, Spiegelman D, Barbieri RL, Dowsett M, Hankinson SE (2006) Endogenous steroid hormone concentrations and risk of breast cancer among premonopausal women. J Nat Cancer Inst 98(19):1406–1415

    Article  PubMed  CAS  Google Scholar 

  17. Yen HY, Gabet Y, Liu Y, Martin A, Wu NL, Pike MC, Frenkel B, Maxson R, Dubeau L (2012) Alterations in Brca1 expression in mouse ovarian granulosa cells have short-term and long-term consequences on estrogen-responsive organs. Lab Invest 92(6):802–811

    Article  PubMed  CAS  Google Scholar 

  18. Bramley M, Clarke RB, Howell A, Evans DG, Armer T, Baildam AD, Anderson E (2006) Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations. Br J Cancer 94(7):1021–1028

    Article  PubMed  CAS  Google Scholar 

  19. Hong H, Yen HY, Brockmeyer A, Liu Y, Chodankar R, Pike MC, Stanczyk FZ, Maxson R, Dubeau L (2010) Changes in the mouse estrus cycle in response to BRCA1 inactivation suggest a potential link between risk factors for familial and sporadic ovarian cancer. Cancer Res 70(1):221–228

    Article  PubMed  CAS  Google Scholar 

  20. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22(12):2328–2335

    Article  PubMed  CAS  Google Scholar 

  21. Williamson LM, Lees-Miller SP (2011) Estrogen receptor alpha-mediated transcription induces cell cycle-dependent DNA double-strand breaks. Carcinogenesis 32(3):279–285

    Article  PubMed  CAS  Google Scholar 

  22. Patel KJ, Yu VP, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BA, Venkitaraman AR (1998) Involvement of Brca2 in DNA repair. Mol Cell 1(3):347–357

    Article  PubMed  CAS  Google Scholar 

  23. Frankish H (2001) BRCA1 has a pivotal role in repairing DNA. Lancet 357(9269):1678

    Google Scholar 

  24. Lonning PE, Helle H, Duong NK, Ekse D, Aas T, Geisler J (2009) Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status. J Steroid Biochem Mol Biol 117(1–3):31–41

    Article  PubMed  CAS  Google Scholar 

  25. Farhat GN, Cummings SR, Chlebowski RT, Parimi N, Cauley JA, Rohan TE, Huang AJ, Vitolins M, Hubbell FA, Manson JE et al (2011) Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst 103(7):562–570

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interests

The authors declare they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics & Gynecology, New York Medical College and Institute for Fertility Preservation, Rye, NY, USA

    Jayeon Kim & Kutluk Oktay

Authors
  1. Jayeon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kutluk Oktay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kutluk Oktay.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1 Basal E2 levels of BRCA mutation carriers (DOC 38 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J., Oktay, K. Baseline E2 levels are higher in BRCA2 mutation carriers: a potential target for prevention?. Cancer Causes Control 24, 421–426 (2013). https://doi.org/10.1007/s10552-012-0127-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-012-0127-3

Keywords

Search

Navigation