Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations

A case-control study

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, D. Horsman, B. Rosen, C. Isaacs & 34 others S. Domchek, R. Gershoni-Baruch, A. Eisen, O. I. Olopade, E. Friedman, H. M. Saal, S. L. Neuhausen, M. Daly, B. Karlan, R. N. Kurz, C. Bellati, C. Eng, K. Sweet, T. Wagner, G. Rennert, D. Provencher, C. Maugard, J. Garber, W. McKinnon, M. Wood, D. Gilchrist, M. Osborne, J. McLennan, S. Merajver, B. Pasche, T. Fallen, E. Lemire, A. Chudley, J. Weitzel, W. S. Meschino, D. Rayson, G. Evans, D. Agnese, H. Olsson

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1111-1119
Number of pages9
JournalCancer Causes and Control
Volume19
Issue number10
DOIs
StatePublished - Dec 2008

Fingerprint

Neoplasm Genes
Infertility
Case-Control Studies
Breast Neoplasms
Fertility
Mutation
Therapeutics
Odds Ratio
Confidence Intervals
Fertilization in Vitro
Parity
Ovarian Neoplasms
Estrogens

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kotsopoulos, J., Librach, C. L., Lubinski, J., Gronwald, J., Kim-Sing, C., Ghadirian, P., ... Olsson, H. (2008). Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: A case-control study. Cancer Causes and Control, 19(10), 1111-1119. https://doi.org/10.1007/s10552-008-9175-0

Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations : A case-control study. / Kotsopoulos, Joanne; Librach, Clifford L.; Lubinski, Jan; Gronwald, Jacek; Kim-Sing, Charmaine; Ghadirian, Parviz; Lynch, Henry T.; Moller, Pal; Foulkes, William D.; Randall, Susan; Manoukian, Siranoush; Pasini, Barbara; Tung, Nadine; Ainsworth, Peter J.; Cummings, Shelly; Sun, Ping; Narod, Steven A.; Horsman, D.; Rosen, B.; Isaacs, C.; Domchek, S.; Gershoni-Baruch, R.; Eisen, A.; Olopade, O. I.; Friedman, E.; Saal, H. M.; Neuhausen, S. L.; Daly, M.; Karlan, B.; Kurz, R. N.; Bellati, C.; Eng, C.; Sweet, K.; Wagner, T.; Rennert, G.; Provencher, D.; Maugard, C.; Garber, J.; McKinnon, W.; Wood, M.; Gilchrist, D.; Osborne, M.; McLennan, J.; Merajver, S.; Pasche, B.; Fallen, T.; Lemire, E.; Chudley, A.; Weitzel, J.; Meschino, W. S.; Rayson, D.; Evans, G.; Agnese, D.; Olsson, H.

In: Cancer Causes and Control, Vol. 19, No. 10, 12.2008, p. 1111-1119.

Research output: Contribution to journalArticle

Kotsopoulos, J, Librach, CL, Lubinski, J, Gronwald, J, Kim-Sing, C, Ghadirian, P, Lynch, HT, Moller, P, Foulkes, WD, Randall, S, Manoukian, S, Pasini, B, Tung, N, Ainsworth, PJ, Cummings, S, Sun, P, Narod, SA, Horsman, D, Rosen, B, Isaacs, C, Domchek, S, Gershoni-Baruch, R, Eisen, A, Olopade, OI, Friedman, E, Saal, HM, Neuhausen, SL, Daly, M, Karlan, B, Kurz, RN, Bellati, C, Eng, C, Sweet, K, Wagner, T, Rennert, G, Provencher, D, Maugard, C, Garber, J, McKinnon, W, Wood, M, Gilchrist, D, Osborne, M, McLennan, J, Merajver, S, Pasche, B, Fallen, T, Lemire, E, Chudley, A, Weitzel, J, Meschino, WS, Rayson, D, Evans, G, Agnese, D & Olsson, H 2008, 'Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: A case-control study', Cancer Causes and Control, vol. 19, no. 10, pp. 1111-1119. https://doi.org/10.1007/s10552-008-9175-0
Kotsopoulos, Joanne ; Librach, Clifford L. ; Lubinski, Jan ; Gronwald, Jacek ; Kim-Sing, Charmaine ; Ghadirian, Parviz ; Lynch, Henry T. ; Moller, Pal ; Foulkes, William D. ; Randall, Susan ; Manoukian, Siranoush ; Pasini, Barbara ; Tung, Nadine ; Ainsworth, Peter J. ; Cummings, Shelly ; Sun, Ping ; Narod, Steven A. ; Horsman, D. ; Rosen, B. ; Isaacs, C. ; Domchek, S. ; Gershoni-Baruch, R. ; Eisen, A. ; Olopade, O. I. ; Friedman, E. ; Saal, H. M. ; Neuhausen, S. L. ; Daly, M. ; Karlan, B. ; Kurz, R. N. ; Bellati, C. ; Eng, C. ; Sweet, K. ; Wagner, T. ; Rennert, G. ; Provencher, D. ; Maugard, C. ; Garber, J. ; McKinnon, W. ; Wood, M. ; Gilchrist, D. ; Osborne, M. ; McLennan, J. ; Merajver, S. ; Pasche, B. ; Fallen, T. ; Lemire, E. ; Chudley, A. ; Weitzel, J. ; Meschino, W. S. ; Rayson, D. ; Evans, G. ; Agnese, D. ; Olsson, H. / Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations : A case-control study. In: Cancer Causes and Control. 2008 ; Vol. 19, No. 10. pp. 1111-1119.
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title = "Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: A case-control study",
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.",
author = "Joanne Kotsopoulos and Librach, {Clifford L.} and Jan Lubinski and Jacek Gronwald and Charmaine Kim-Sing and Parviz Ghadirian and Lynch, {Henry T.} and Pal Moller and Foulkes, {William D.} and Susan Randall and Siranoush Manoukian and Barbara Pasini and Nadine Tung and Ainsworth, {Peter J.} and Shelly Cummings and Ping Sun and Narod, {Steven A.} and D. Horsman and B. Rosen and C. Isaacs and S. Domchek and R. Gershoni-Baruch and A. Eisen and Olopade, {O. I.} and E. Friedman and Saal, {H. M.} and Neuhausen, {S. L.} and M. Daly and B. Karlan and Kurz, {R. N.} and C. Bellati and C. Eng and K. Sweet and T. Wagner and G. Rennert and D. Provencher and C. Maugard and J. Garber and W. McKinnon and M. Wood and D. Gilchrist and M. Osborne and J. McLennan and S. Merajver and B. Pasche and T. Fallen and E. Lemire and A. Chudley and J. Weitzel and Meschino, {W. S.} and D. Rayson and G. Evans and D. Agnese and H. Olsson",
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TY - JOUR

T1 - Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations

T2 - A case-control study

AU - Kotsopoulos, Joanne

AU - Librach, Clifford L.

AU - Lubinski, Jan

AU - Gronwald, Jacek

AU - Kim-Sing, Charmaine

AU - Ghadirian, Parviz

AU - Lynch, Henry T.

AU - Moller, Pal

AU - Foulkes, William D.

AU - Randall, Susan

AU - Manoukian, Siranoush

AU - Pasini, Barbara

AU - Tung, Nadine

AU - Ainsworth, Peter J.

AU - Cummings, Shelly

AU - Sun, Ping

AU - Narod, Steven A.

AU - Horsman, D.

AU - Rosen, B.

AU - Isaacs, C.

AU - Domchek, S.

AU - Gershoni-Baruch, R.

AU - Eisen, A.

AU - Olopade, O. I.

AU - Friedman, E.

AU - Saal, H. M.

AU - Neuhausen, S. L.

AU - Daly, M.

AU - Karlan, B.

AU - Kurz, R. N.

AU - Bellati, C.

AU - Eng, C.

AU - Sweet, K.

AU - Wagner, T.

AU - Rennert, G.

AU - Provencher, D.

AU - Maugard, C.

AU - Garber, J.

AU - McKinnon, W.

AU - Wood, M.

AU - Gilchrist, D.

AU - Osborne, M.

AU - McLennan, J.

AU - Merajver, S.

AU - Pasche, B.

AU - Fallen, T.

AU - Lemire, E.

AU - Chudley, A.

AU - Weitzel, J.

AU - Meschino, W. S.

AU - Rayson, D.

AU - Evans, G.

AU - Agnese, D.

AU - Olsson, H.

PY - 2008/12

Y1 - 2008/12

N2 - 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.

AB - 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.

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