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Published in: Breast Cancer 4/2015

01-07-2015 | Review Article

Tamoxifen and risk of contralateral breast cancer among women with inherited mutations in BRCA1 and BRCA2: a meta-analysis

Authors: Lingyun Xu, Yansheng Zhao, Zhiqiang Chen, Yujiao Wang, Lin Chen, Shui Wang

Published in: Breast Cancer | Issue 4/2015

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Abstract

Given the greatly elevated risks of contralateral breast cancer (CBC) observed in breast cancer patients who carry mutation in BRCA1 or BRCA2, the present meta-analysis was addressed to determine whether adjuvant tamoxifen treatment for breast cancer is associated with reduced CBC risk for these patients. We searched the database of PubMed for eligible studies about the effectiveness of tamoxifen on CBC risk among BRCA1/2 mutation carriers, and we calculated the pooled relative risks (RRs) for CBC risk along with 95 % confidence intervals (CIs). Fixed- or random-effects model was conducted according to study heterogeneity. Four non-overlapping studies met the inclusion criteria for the meta-analysis. Tamoxifen was found to be significantly associated with reduced risk of CBC among BRCA1/2 mutation carriers (summary RR = 0.56, 95 % CI = 0.41–0.76). Similar findings were observed in BRCA1 mutation carriers (summary RR = 0.47, 95 % CI = 0.37–0.60) and BRCA2 mutation carriers (summary RR = 0.39, 95 % CI = 0.28–0.54), respectively. In conclusion, tamoxifen significantly reduces the incidence of CBC among BRCA1/2 mutation carriers with primary unilateral breast cancer. It can reasonably be offered to breast cancer patients with BRCA1 or BRCA2 mutation for the prevention of CBC. Further studies are required to get a more precise estimation of the benefits and harms of tamoxifen in these patients.
Literature
1.
go back to reference Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, et al. 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. 2003;72:1117–30.PubMedCentralPubMedCrossRef Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, et al. 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. 2003;72:1117–30.PubMedCentralPubMedCrossRef
3.
go back to reference Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35–64 years. Cancer Res. 2006;66:8297–308.PubMedCrossRef Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35–64 years. Cancer Res. 2006;66:8297–308.PubMedCrossRef
4.
go back to reference Malone KE, Begg CB, Haile RW, Borg A, Concannon P, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.PubMedCentralPubMedCrossRef Malone KE, Begg CB, Haile RW, Borg A, Concannon P, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.PubMedCentralPubMedCrossRef
5.
go back to reference Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–35.PubMedCrossRef Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–35.PubMedCrossRef
6.
go back to reference Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24:2437–43.PubMedCrossRef Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24:2437–43.PubMedCrossRef
7.
go back to reference Verhoog LC, Brekelmans CT, Seynaeve C, Meijers-Heijboer EJ, Klijn JG. Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer. 2000;83:384–6.PubMedCentralPubMedCrossRef Verhoog LC, Brekelmans CT, Seynaeve C, Meijers-Heijboer EJ, Klijn JG. Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer. 2000;83:384–6.PubMedCentralPubMedCrossRef
8.
go back to reference Collins IM, Milne RL, Weideman PC, McLachlan SA, Friedlander ML, et al. Preventing breast and ovarian cancers in high-risk BRCA1 and BRCA2 mutation carriers. Med J Aust. 2013;199:680–3.PubMedCrossRef Collins IM, Milne RL, Weideman PC, McLachlan SA, Friedlander ML, et al. Preventing breast and ovarian cancers in high-risk BRCA1 and BRCA2 mutation carriers. Med J Aust. 2013;199:680–3.PubMedCrossRef
9.
go back to reference Rutqvist LE, Cedermark B, Glas U, Mattsson A, Skoog L, et al. Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy. J Natl Cancer Inst. 1991;83:1299–306.PubMedCrossRef Rutqvist LE, Cedermark B, Glas U, Mattsson A, Skoog L, et al. Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy. J Natl Cancer Inst. 1991;83:1299–306.PubMedCrossRef
10.
go back to reference Reding KW, Bernstein JL, Langholz BM, Bernstein L, Haile RW, et al. Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat. 2010;123:491–8.PubMedCentralPubMedCrossRef Reding KW, Bernstein JL, Langholz BM, Bernstein L, Haile RW, et al. Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat. 2010;123:491–8.PubMedCentralPubMedCrossRef
11.
go back to reference Gronwald J, Robidoux A, Kim-Sing C, Tung N, Lynch HT, et al. Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2014;146:421–7.PubMedCrossRef Gronwald J, Robidoux A, Kim-Sing C, Tung N, Lynch HT, et al. Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2014;146:421–7.PubMedCrossRef
12.
go back to reference Phillips KA, Milne RL, Rookus MA, Daly MB, Antoniou AC, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091–9.PubMedCentralPubMedCrossRef Phillips KA, Milne RL, Rookus MA, Daly MB, Antoniou AC, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091–9.PubMedCentralPubMedCrossRef
13.
go back to reference Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet. 2000;356:1876–81.PubMedCrossRef Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet. 2000;356:1876–81.PubMedCrossRef
14.
go back to reference Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281–4.PubMedCrossRef Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281–4.PubMedCrossRef
15.
go back to reference Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–6.PubMedCrossRef Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–6.PubMedCrossRef
16.
go back to reference Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMed Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMed
17.
18.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef
20.
go back to reference LaCroix AZ, Powles T, Osborne CK, Wolter K, Thompson JR, et al. Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst. 2010;102:1706–15.PubMedCrossRef LaCroix AZ, Powles T, Osborne CK, Wolter K, Thompson JR, et al. Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst. 2010;102:1706–15.PubMedCrossRef
21.
go back to reference Martino S, Costantino J, McNabb M, Mershon J, Bryant K, et al. The role of selective estrogen receptor modulators in the prevention of breast cancer: comparison of the clinical trials. Oncologist. 2004;9:116–25.PubMedCrossRef Martino S, Costantino J, McNabb M, Mershon J, Bryant K, et al. The role of selective estrogen receptor modulators in the prevention of breast cancer: comparison of the clinical trials. Oncologist. 2004;9:116–25.PubMedCrossRef
22.
go back to reference Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652–62.PubMedCrossRef Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652–62.PubMedCrossRef
23.
go back to reference Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355:125–37.PubMedCrossRef Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355:125–37.PubMedCrossRef
24.
go back to reference Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359:697–708.PubMedCentralPubMedCrossRef Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359:697–708.PubMedCentralPubMedCrossRef
25.
go back to reference Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364:2381–91.PubMedCrossRef Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364:2381–91.PubMedCrossRef
26.
go back to reference Johannsson OT, Idvall I, Anderson C, Borg A, Barkardottir RB, et al. Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer. 1997;33:362–71.PubMedCrossRef Johannsson OT, Idvall I, Anderson C, Borg A, Barkardottir RB, et al. Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer. 1997;33:362–71.PubMedCrossRef
27.
go back to reference Robson M, Gilewski T, Haas B, Levin D, Borgen P, et al. BRCA-associated breast cancer in young women. J Clin Oncol. 1998;16:1642–9.PubMed Robson M, Gilewski T, Haas B, Levin D, Borgen P, et al. BRCA-associated breast cancer in young women. J Clin Oncol. 1998;16:1642–9.PubMed
28.
go back to reference Ansquer Y, Gautier C, Fourquet A, Asselain B, Stoppa-Lyonnet D. Survival in early-onset BRCA1 breast-cancer patients. Institut Curie Breast Cancer Group. Lancet. 1998;352:541. Ansquer Y, Gautier C, Fourquet A, Asselain B, Stoppa-Lyonnet D. Survival in early-onset BRCA1 breast-cancer patients. Institut Curie Breast Cancer Group. Lancet. 1998;352:541.
29.
go back to reference Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd Ouweland A, Menke-Pluymers MB, et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer. 2007;43:867–76.PubMedCrossRef Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd Ouweland A, Menke-Pluymers MB, et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer. 2007;43:867–76.PubMedCrossRef
30.
go back to reference Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381:1827–34.PubMedCentralPubMedCrossRef Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381:1827–34.PubMedCentralPubMedCrossRef
31.
go back to reference Li CI, Malone KE, Weiss NS, Daling JR. Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst. 2001;93:1008–13.PubMedCrossRef Li CI, Malone KE, Weiss NS, Daling JR. Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst. 2001;93:1008–13.PubMedCrossRef
32.
go back to reference Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26:1331–7.PubMedCentralPubMedCrossRef Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26:1331–7.PubMedCentralPubMedCrossRef
33.
go back to reference Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol. 2005;23:7491–6.PubMedCrossRef Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol. 2005;23:7491–6.PubMedCrossRef
34.
go back to reference Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75.PubMedCentralPubMedCrossRef Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75.PubMedCentralPubMedCrossRef
35.
go back to reference Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, Ausems MG, Collee JM, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 2015;107(5). doi:10.1093/jnci/djv033. Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, Ausems MG, Collee JM, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 2015;107(5). doi:10.​1093/​jnci/​djv033.
36.
go back to reference Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci USA. 2007;104:5455–60.PubMedCentralPubMedCrossRef Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci USA. 2007;104:5455–60.PubMedCentralPubMedCrossRef
37.
go back to reference Harrison H, Simoes BM, Rogerson L, Howell SJ, Landberg G, et al. Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling. Breast Cancer Res. 2013;15:R21.PubMedCentralPubMedCrossRef Harrison H, Simoes BM, Rogerson L, Howell SJ, Landberg G, et al. Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling. Breast Cancer Res. 2013;15:R21.PubMedCentralPubMedCrossRef
38.
go back to reference Eakin CM, Maccoss MJ, Finney GL, Klevit RE. Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase. Proc Natl Acad Sci USA. 2007;104:5794–9.PubMedCentralPubMedCrossRef Eakin CM, Maccoss MJ, Finney GL, Klevit RE. Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase. Proc Natl Acad Sci USA. 2007;104:5794–9.PubMedCentralPubMedCrossRef
39.
go back to reference Fan S, Wang J, Yuan R, Ma Y, Meng Q, et al. BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science. 1999;284:1354–6.PubMedCrossRef Fan S, Wang J, Yuan R, Ma Y, Meng Q, et al. BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science. 1999;284:1354–6.PubMedCrossRef
40.
go back to reference Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041–8.PubMedCrossRef Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041–8.PubMedCrossRef
41.
go back to reference Metcalfe KA, Snyder C, Seidel J, Hanna D, Lynch HT, et al. The use of preventive measures among healthy women who carry a BRCA1 or BRCA2 mutation. Fam Cancer. 2005;4:97–103.PubMedCrossRef Metcalfe KA, Snyder C, Seidel J, Hanna D, Lynch HT, et al. The use of preventive measures among healthy women who carry a BRCA1 or BRCA2 mutation. Fam Cancer. 2005;4:97–103.PubMedCrossRef
Metadata
Title
Tamoxifen and risk of contralateral breast cancer among women with inherited mutations in BRCA1 and BRCA2: a meta-analysis
Authors
Lingyun Xu
Yansheng Zhao
Zhiqiang Chen
Yujiao Wang
Lin Chen
Shui Wang
Publication date
01-07-2015
Publisher
Springer Japan
Published in
Breast Cancer / Issue 4/2015
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-015-0619-6

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