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Erschienen in: Breast Cancer Research and Treatment 1/2011

01.05.2011 | Brief Report

Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers

verfasst von: Kelly Metcalfe, Henry T. Lynch, Parviz Ghadirian, Nadine Tung, Charmaine Kim-Sing, Olufunmilayo I. Olopade, Susan Domchek, Andrea Eisen, William D. Foulkes, Barry Rosen, Danny Vesprini, Ping Sun, Steven A. Narod

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2011

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Abstract

Women with a BRCA1 or BRCA2 mutation have an elevated risk of breast cancer and of contralateral breast cancer. In this study, we estimate the risk of non-synchronous ipsilateral breast cancer after a diagnosis of breast cancer in BRCA carriers and evaluate the effects of various treatments on this risk. Patients were 396 women with stage I or stage II breast cancer with an intact ipsilateral breast and for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until the first of ipsilateral mastectomy, ipsilateral breast cancer, death or last follow-up. The 5-year actuarial risk of ipsilateral breast cancer was 5.8% (95% CI 3.2–8.4%) and the 10-year risk was 12.9% (95% CI 8.7–17.1%). Subjects who received chemotherapy had a significantly lower risk of ipsilateral breast cancer compared to those who did not receive chemotherapy (RR 0.45; 95% CI 0.24–0.84; P = 0.01). Radiotherapy was associated with a reduced risk of ipsilateral breast cancer (RR 0.28; 95% CI 0.12–0.63; P = 0.002). Oophorectomy was associated with a significant reduction in the risk of ipsilateral breast cancer (RR 0.33; 95% CI; 0.13–0.81; P = 0.02). On average, following a diagnosis of breast cancer, the annual risk of ipsilateral breast cancer risk in BRCA mutation carriers is 1.2% per year. For women treated with chemotherapy, radiation therapy or oophorectomy the risk is low, compared to women who did not receive any of these treatments.
Literatur
1.
Zurück zum Zitat Antoniou A, Pharoah PD, Narod S (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 72:1117–1130PubMedCrossRef Antoniou A, Pharoah PD, Narod S (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 72:1117–1130PubMedCrossRef
2.
Zurück zum Zitat Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333PubMedCrossRef Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333PubMedCrossRef
3.
Zurück zum Zitat Verhoog LC, Brekelmans CT, Seynaeve C et al (1998) Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316–321PubMedCrossRef Verhoog LC, Brekelmans CT, Seynaeve C et al (1998) Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316–321PubMedCrossRef
4.
Zurück zum Zitat Robson M, Gilewski T, Haas B et al (1998) BRCA-associated breast cancer in young women. J Clin Oncol 16:1642–1649PubMed Robson M, Gilewski T, Haas B et al (1998) BRCA-associated breast cancer in young women. J Clin Oncol 16:1642–1649PubMed
5.
Zurück zum Zitat Verhoog LC, Brekelmans CT, Seynaeve C et al (2000) Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer 83:384–386PubMedCrossRef Verhoog LC, Brekelmans CT, Seynaeve C et al (2000) Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer 83:384–386PubMedCrossRef
6.
Zurück zum Zitat Haffty BG, Harrold E, Khan AJ et al (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477PubMedCrossRef Haffty BG, Harrold E, Khan AJ et al (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477PubMedCrossRef
7.
Zurück zum Zitat Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C et al (2007) 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 43:867–876PubMedCrossRef Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C et al (2007) 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 43:867–876PubMedCrossRef
8.
Zurück zum Zitat Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:5887–5892PubMedCrossRef Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:5887–5892PubMedCrossRef
9.
Zurück zum Zitat Metcalfe K, Lynch HT, Ghadirian P et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22:2328–2335PubMedCrossRef Metcalfe K, Lynch HT, Ghadirian P et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22:2328–2335PubMedCrossRef
10.
Zurück zum Zitat Metcalfe K, Gershman S, Lynch HT et al Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers (submitted) Metcalfe K, Gershman S, Lynch HT et al Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers (submitted)
11.
Zurück zum Zitat Brekelmans CT, Seynaeve C, Menke-Pluymers M et al (2006) Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol 17:391–400PubMedCrossRef Brekelmans CT, Seynaeve C, Menke-Pluymers M et al (2006) Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol 17:391–400PubMedCrossRef
12.
Zurück zum Zitat Seynaeve C, Verhoog LC, van de Bosch LM et al (2004) Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. Eur J Cancer 40:1150–1158PubMedCrossRef Seynaeve C, Verhoog LC, van de Bosch LM et al (2004) Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. Eur J Cancer 40:1150–1158PubMedCrossRef
13.
Zurück zum Zitat Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6:R8–R17PubMedCrossRef Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6:R8–R17PubMedCrossRef
14.
Zurück zum Zitat Robson M, Svahn T, McCormick B et al (2005) Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer 103:44–51PubMedCrossRef Robson M, Svahn T, McCormick B et al (2005) Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer 103:44–51PubMedCrossRef
15.
Zurück zum Zitat Pierce LJ, Levin AM, Rebbeck TR et al (2006) Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24:2437–2443PubMedCrossRef Pierce LJ, Levin AM, Rebbeck TR et al (2006) Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24:2437–2443PubMedCrossRef
16.
Zurück zum Zitat Eccles D, Simmonds P, Goddard J et al (2001) Familial breast cancer: an investigation into the outcome of treatment for early stage disease. Fam Cancer 1:65–72PubMedCrossRef Eccles D, Simmonds P, Goddard J et al (2001) Familial breast cancer: an investigation into the outcome of treatment for early stage disease. Fam Cancer 1:65–72PubMedCrossRef
17.
Zurück zum Zitat Donegan WL, Perez-Mesa CM, Watson FR (1966) A biostatistical study of locally recurrent breast carcinoma. Surg Gynecol Obstet 122:529–540PubMed Donegan WL, Perez-Mesa CM, Watson FR (1966) A biostatistical study of locally recurrent breast carcinoma. Surg Gynecol Obstet 122:529–540PubMed
18.
Zurück zum Zitat Pierce LJ, Phillips KA, Griffith KA et al (2010) Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 121:389–398PubMedCrossRef Pierce LJ, Phillips KA, Griffith KA et al (2010) Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 121:389–398PubMedCrossRef
19.
Zurück zum Zitat Domchek SM, Friebel TM, Singer CF (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975PubMedCrossRef Domchek SM, Friebel TM, Singer CF (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975PubMedCrossRef
20.
Zurück zum Zitat Rebbeck TR, Levin AM, Eisen A et al (1999) Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 91:1475–1479PubMedCrossRef Rebbeck TR, Levin AM, Eisen A et al (1999) Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 91:1475–1479PubMedCrossRef
21.
Zurück zum Zitat Eisen A, Lubinski J, Klijn J et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23:7491–7496PubMedCrossRef Eisen A, Lubinski J, Klijn J et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23:7491–7496PubMedCrossRef
22.
Zurück zum Zitat Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101:80–87PubMedCrossRef Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101:80–87PubMedCrossRef
23.
Zurück zum Zitat Chappuis PO, Goffin J, Wong N et al (2002) A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J Med Genet 39:608–610PubMedCrossRef Chappuis PO, Goffin J, Wong N et al (2002) A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J Med Genet 39:608–610PubMedCrossRef
24.
Zurück zum Zitat Fourquet A, Stoppa-Lyonnet D, Kirova YM et al (2009) Familial breast cancer: clinical response to induction chemotherapy or radiotherapy related to BRCA1/2 mutations status. Am J Clin Oncol 32:127–131PubMedCrossRef Fourquet A, Stoppa-Lyonnet D, Kirova YM et al (2009) Familial breast cancer: clinical response to induction chemotherapy or radiotherapy related to BRCA1/2 mutations status. Am J Clin Oncol 32:127–131PubMedCrossRef
25.
Zurück zum Zitat Wong Wong Keet A, Al-Rafae M, Chappuis PO, Brunet JS, Ghadirian P, Foulkes WD (2009) Long-term outcome after neo-adjuvant chemotherapy for breast cancer in BRCA1/2 carriers. Int J Cancer 125:2236–2238PubMedCrossRef Wong Wong Keet A, Al-Rafae M, Chappuis PO, Brunet JS, Ghadirian P, Foulkes WD (2009) Long-term outcome after neo-adjuvant chemotherapy for breast cancer in BRCA1/2 carriers. Int J Cancer 125:2236–2238PubMedCrossRef
26.
Zurück zum Zitat Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668PubMedCrossRef Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668PubMedCrossRef
27.
Zurück zum Zitat Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK (2000) The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem 275:23899–23903PubMedCrossRef Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK (2000) The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem 275:23899–23903PubMedCrossRef
28.
Zurück zum Zitat Thangaraju M, Kaufmann SH, Couch FJ (2000) BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell lines. J Biol Chem 275:33487–33496PubMedCrossRef Thangaraju M, Kaufmann SH, Couch FJ (2000) BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell lines. J Biol Chem 275:33487–33496PubMedCrossRef
29.
Zurück zum Zitat Freneaux P, Stoppa-Lyonnet D, Mouret E et al (2000) Low expression of bcl-2 in Brca1-associated breast cancers. Br J Cancer 83:1318–1322PubMedCrossRef Freneaux P, Stoppa-Lyonnet D, Mouret E et al (2000) Low expression of bcl-2 in Brca1-associated breast cancers. Br J Cancer 83:1318–1322PubMedCrossRef
30.
Zurück zum Zitat Quinn JE, Kennedy RD, Mullan PB et al (2003) BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 6319:6221–6228 Quinn JE, Kennedy RD, Mullan PB et al (2003) BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 6319:6221–6228
31.
Zurück zum Zitat Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28:375–379PubMedCrossRef Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28:375–379PubMedCrossRef
32.
Zurück zum Zitat Clarke M, Collins R, Darby S et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106PubMed Clarke M, Collins R, Darby S et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106PubMed
33.
Zurück zum Zitat Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434PubMedCrossRef Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434PubMedCrossRef
34.
Zurück zum Zitat Brenner DJ, Shuryak I (2007) Reducing second primary breast cancers: a potential role for prophylactic mammary irradiation. J Clin Oncol 25:4868–4872PubMedCrossRef Brenner DJ, Shuryak I (2007) Reducing second primary breast cancers: a potential role for prophylactic mammary irradiation. J Clin Oncol 25:4868–4872PubMedCrossRef
Metadaten
Titel
Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers
verfasst von
Kelly Metcalfe
Henry T. Lynch
Parviz Ghadirian
Nadine Tung
Charmaine Kim-Sing
Olufunmilayo I. Olopade
Susan Domchek
Andrea Eisen
William D. Foulkes
Barry Rosen
Danny Vesprini
Ping Sun
Steven A. Narod
Publikationsdatum
01.05.2011
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2011
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1336-7

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