Top

Published in:

01-12-2008 | Original Paper

Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case–control study

Authors: Joanne Kotsopoulos, Clifford L. Librach, Jan Lubinski, Jacek Gronwald, Charmaine Kim-Sing, Parviz Ghadirian, Henry T. Lynch, Pal Moller, William D. Foulkes, Susan Randall, Siranoush Manoukian, Barbara Pasini, Nadine Tung, Peter J. Ainsworth, Shelly Cummings, Ping Sun, Steven A. Narod, Hereditary Breast Cancer Clinical Study Group

Published in: Cancer Causes & Control | Issue 10/2008

Abstract

Background

Women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation are at increased risk for developing breast and ovarian cancer. Various reproductive and hormonal factors have been shown to modify the risk of breast cancer. These studies suggest that estrogen exposure and deprivation are important in the etiology of hereditary cancer. Many patients are interested in the possibility of an adverse effect of fertility treatment on breast cancer risk. It is important to evaluate whether or not infertility per se or exposure to fertility medications increase the risk of breast cancer in genetically predisposed women.

Methods

We conducted a matched case–control study of 1,380 pairs of women with a BRCA1 or BRCA2 mutation to determine if a history of infertility, the use of fertility medications, or undergoing in vitro fertilization (IVF) were associated with and increased the risk of breast cancer.

Results

Sixteen percent of the study subjects reported having experienced a fertility problem and 4% had used a fertility medication. Women who had used a fertility medication were not at significantly increased risk of breast cancer (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.81–1.82) compared to non-users. Furthermore, there was no risk associated with a history of use of a fertility medication when the subjects were stratified by parity: (OR = 1.29; 95% CI = 0.83–2.01 for nulliparous women and OR = 0.81; 95% CI = 0.30–2.22 for parous women).

Conclusions

The results of this study suggest that the use of fertility medications does not adversely affect the risk of breast cancer among BRCA mutation carriers. Given the small sizes of the exposed subgroups, these findings should be interpreted with caution and confirmatory studies are required.

Henderson BE et al (1985) Do regular ovulatory cycles increase breast cancer risk? Cancer 56(5):1206–1208. doi:10.1002/1097-0142(19850901)56:5≤1206::AID-CNCR2820560541≥3.0.CO;2-9PubMedCrossRef

Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47PubMed

Lipworth L (1995) Epidemiology of breast cancer. Eur J Cancer Prev 4(1):7–30. doi:10.1097/00008469-199502000-00002 PubMedCrossRef

Klip H et al (2000) Cancer risk associated with subfertility and ovulation induction: a review. Cancer Causes Control 11(4):319–344. doi:10.1023/A:1008921211309 PubMedCrossRef

Venn A, Healy D, McLachlan R (2003) Cancer risks associated with the diagnosis of infertility. Best Pract Res Clin Obstet Gynaecol 17(2):343–367PubMedCrossRef

Salhab M, Al Sarakbi W, Mokbel K (2005) In vitro fertilization and breast cancer risk: a review. Int J Fertil Womens Med 50(6):259–266PubMed

Ford D 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. doi:10.1086/301749 PubMedCrossRef

Risch HA et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710. doi:10.1086/318787 PubMedCrossRef

Antoniou 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. doi:10.1086/375033 PubMedCrossRef

10.

King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646. doi:10.1126/science.1088759 PubMedCrossRef

11.

Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25(43):5832–5836. doi:10.1038/sj.onc.1209870 PubMedCrossRef

12.

Ayhan A et al (2004) Association between fertility drugs and gynecologic cancers, breast cancer, and childhood cancers. Acta Obstet Gynecol Scand 83(12):1104–1111. doi:10.1111/j.0001-6349.2004.00669.x PubMedCrossRef

13.

Lambe M et al (1994) Transient increase in the risk of breast cancer after giving birth. N Engl J Med 331(1):5–9. doi:10.1056/NEJM199407073310102 PubMedCrossRef

14.

Kroman N et al (1997) Time since childbirth and prognosis in primary breast cancer: population based study. BMJ 315(7112):851–855PubMed

15.

Braga C et al (1996) Fertility treatment and risk of breast cancer. Hum Reprod 11(2):300–303PubMed

16.

Grabrick DM et al (2002) Association of correlates of endogenous hormonal exposure with breast cancer risk in 426 families (United States). Cancer Causes Control 13(4):333–341. doi:10.1023/A:1015292724384 PubMedCrossRef

17.

Gauthier E, Paoletti X, Clavel-Chapelon F (2004) Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study. Hum Reprod 19(10):2216–2221. doi:10.1093/humrep/deh422 PubMedCrossRef

18.

Eisen A et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case–control study. J Clin Oncol 23(30):7491–7496. doi:10.1200/JCO.2004.00.7138 PubMedCrossRef

19.

Gronwald J et al (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 118(9):2281–2284. doi:10.1002/ijc.21536 PubMedCrossRef

20.

Kotsopoulos J et al (2005) Age at menarche and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Cancer Causes Control 16(6):667–674. doi:10.1007/s10552-005-1724-1 PubMedCrossRef

21.

Jernstrom H et al (2004) Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 96(14):1094–1098PubMedCrossRef

22.

Cullinane CA et al (2005) Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer 117:988–991

23.

Key TJ, Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24(1):29–43. doi:10.1016/0277-5379(88)90173-3 PubMedCrossRef

24.

Pike MC et al (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15(1):17–35PubMed

25.

Riggs BL, Hartmann LC (2003) Selective estrogen-receptor modulators—mechanisms of action and application to clinical practice. N Engl J Med 348(7):618–629. doi:10.1056/NEJMra022219 PubMedCrossRef

26.

Mokbel K (2003) Risk-reducing strategies for breast cancer—a review of recent literature. Int J Fertil Womens Med 48(6):274–277PubMed

27.

Terry KL et al (2006) A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med 66(22):2484–2489. doi:10.1001/archinte.166.22.2484 CrossRef

28.

Rossing MA et al (1996) Risk of breast cancer in a cohort in infertile women. Gynecol Oncol 60(1):3–7. doi:10.1006/gyno.1996.0002 PubMedCrossRef

29.

Burkman RT et al (2003) Infertility drugs and the risk of breast cancer: findings from the National Institute of Child Health and Human Development Women’s Contraceptive and Reproductive Experiences Study. Fertil Steril 79(4):844–851. doi:10.1016/S0015-0282(02)04950-6 PubMedCrossRef

30.

Haning RV Jr et al (1979) Plasma estradiol window and urinary estriol glucuronide determinations for monitoring menotropin induction of ovulation. Obstet Gynecol 54(4):442–447PubMed

31.

Sallam HN et al (1999) Reference values for the midluteal plasma progesterone concentration: evidence from human menopausal gonadotropin-stimulated pregnancy cycles. Fertil Steril 71(4):711–714. doi:10.1016/S0015-0282(98)00531-7 PubMedCrossRef

Title: Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case–control study
Authors: Joanne Kotsopoulos
Clifford L. Librach
Jan Lubinski
Jacek Gronwald
Charmaine Kim-Sing
Parviz Ghadirian
Henry T. Lynch
Pal Moller
William D. Foulkes
Susan Randall
Siranoush Manoukian
Barbara Pasini
Nadine Tung
Peter J. Ainsworth
Shelly Cummings
Ping Sun
Steven A. Narod
Hereditary Breast Cancer Clinical Study Group
Publication date: 01-12-2008
Publisher: Springer Netherlands
Published in: Cancer Causes & Control / Issue 10/2008
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-008-9175-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 10/2008

Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Trends in testicular germ cell cancer incidence in Australia

Changing incidence of AIDS-related Kaposi sarcoma and non-Hodgkin lymphoma in Ontario, Canada

Prostate cancer screening

Physical activity and head and neck cancer risk

Keynote webinar | Spotlight on antibody–drug conjugates in cancer