nach oben

Erschienen in:

01.11.2011 | Clinical trial

Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations

verfasst von: Soley Bayraktar, Angelica M. Gutierrez-Barrera, Diane Liu, Tunc Tasbas, Ugur Akar, Jennifer K. Litton, E. Lin, Constance T. Albarracin, Funda Meric-Bernstam, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, Banu K. Arun

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

Einloggen, um Zugang zu erhalten

Abstract

More than 75% of breast cancers that develop in BRCA1 mutation carriers are triple-negative breast cancers (TNBC). The aim of this study was to compare the recurrence-free survival (RFS) and overall survival (OS) in high-risk patients with TNBC with and without deleterious BRCA1/2 mutations. A total of 227 women with TNBC who were referred for genetic counseling and underwent BRCA genetic testing between 1997 and 2010 were included in the study. The relationships between clinical variables and outcomes were evaluated using univariate and multivariate Cox proportional hazard regression models. Of 227 high-risk women with TNBC, 50% (n = 114) tested positive for BRCA1/2 mutations. Age, race, and tumor characteristics did not differ between BRCA non-carriers and carriers. At a median follow-up of 3.4 years, the 5-year RFS rates were 74 and 81% (P = 0.21), and 5-year OS rates were 85 and 93% in BRCA non-carriers and BRCA carriers, respectively (P = 0.11). In a multivariate model, after adjusting for age and disease stage, BRCA carriers tended to have a decreased risk of recurrence (HR = 0.67; 95% CI: 0.38–1.19; P = 0.17) or death (HR = 0.51; 95% CI:0.23–1.17; P = 0.11) compared to non-carriers. Our data indicate a 50% prevalence of deleterious BRCA1/2 mutations in high-risk women diagnosed with TNBC. Overall prognosis of TNBC in BRCA carriers and non-carriers is not significantly different within the first 5 years following an initial diagnosis. Further studies need to evaluate whether different therapies will change the outcome in these subgroups of TNBC.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef

Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26:2568–2581PubMedCrossRef

Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P, Birnbaum D (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240PubMedCrossRef

Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M, Akslen LA (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485PubMed

Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T et al (2005) Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11:5175–5180PubMedCrossRef

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423PubMedCrossRef

Reis-Filho JS, Tutt AN (2008) Triple negative tumours: a critical review. Histopathology 52:108–118PubMedCrossRef

Nicoletto MO, Donach M, De Nicolo A, Artioli G, Banna G, Monfardini S (2001) BRCA-1 and BRCA-2 mutations as prognostic factors in clinical practice and genetic counselling. Cancer Treat Rev 27:295–304PubMedCrossRef

Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, Hudis C, Roberge D, Norton L, Begin LR, Offit K, Foulkes WD (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

10.

Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, Narod SA (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:115–123PubMedCrossRef

11.

Foulkes WD, Metcalfe K, Sun P, Hanna WM, Lynch HT, Ghadirian P, Tung N, Olopade OI, Weber BL, McLennan J, Olivotto IA, Begin LR, Narod SA (2004) Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. Clin Cancer Res 10:2029–2034PubMedCrossRef

12.

Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 4:814–819PubMedCrossRef

13.

Singletary SE, Greene FL (2003) Revision of breast cancer staging: the 6th edition of the TNM Classification. Semin Surg Oncol 21:53–59PubMedCrossRef

14.

Black MM, Speer FD (1957) Nuclear structure in cancer tissues. Surg Gynecol Obstet 105:97–102PubMed

15.

Chang J, Hilsenbeck SG, Sng JH, Wong J, Ragu GC (2001) Pathological features and BRCA1 mutation screening in premenopausal breast cancer patients. Clin Cancer Res 7:1739–1742PubMed

16.

Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W, Toppmeyer D (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652–5657PubMedCrossRef

17.

Lidereau R, Eisinger F, Champeme MH, Nogues C, Bieche I, Birnbaum D, Pallud C, Jacquemier J, Sobol H (2000) Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer. Cancer Res 60:1206–1210PubMed

18.

Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, Brooks KA, Cohen S, Tenenholz B, Desai D, Zandvakili I, Royer R, Li S, Narod SA (2009) The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9:86PubMedCrossRef

19.

Kandel MJ, Stadler ZK, Masciari S et al (2006) Prevalence of BRCA1 mutations in triple negative breast cancer. Proc Am Soc Clin Oncol I 24:18S

20.

Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, Lanchbury JS, Stemke-Hale K, Hennessy BT, Arun BK, Hortobagyi GN, Do KA, Mills GB, Meric-Bernstam F (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17:1082–1089PubMedCrossRef

21.

Kwon JS, Gutierrez-Barrera AM, Young D, Sun CC, Daniels MS, Lu KH, Arun B (2010) Expanding the criteria for BRCA mutation testing in breast cancer survivors. J Clin Oncol 28:4214–4220PubMedCrossRef

22.

Oncology. (2011) NCCNNGi: genetic/familial high-risk assessment: breast and ovarian version 1

23.

Tischkowitz M, Brunet JS, Begin LR, Huntsman DG, Cheang MC, Akslen LA, Nielsen TO, Foulkes WD (2007) Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer 7:134PubMedCrossRef

24.

Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14:1368–1376PubMedCrossRef

25.

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

26.

Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281PubMedCrossRef

27.

Kennedy RDQJ, Johnston PH, Harkin DP (2002) BRCA1: mechanisms of inactivation and implications for management of patients. Lancet 360:1007–1014PubMedCrossRef

28.

Verhoog LC, Seynaeve C, Dahmen G, van Geel AN, Bartels CC et al (1999) Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 17:3396–3402PubMed

29.

Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd Ouweland A, Menke-Pluymers MB, Bartels CC 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. B Eur J Cancer 43:867–876CrossRef

30.

Kriege M, Seynaeve C, Meijers-Heijboer H, Collee JM, Menke-Pluymers MB, Bartels CC et al (2008) Distant disease-free interval, site of first relapse and post-relapse survival in B. Breast Cancer Res Treat 111:303–311PubMedCrossRef

31.

Bonadona V, Dossart MS, Voirin N, Sinilnikova OM, Mignotte H, Mathevet P, Bremond A, Treilleux I, Martin A, Romestaing P et al (2007) Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review. Breast Cancer Res Treat 101:233–245PubMedCrossRef

32.

Bordeleau L, Panchal S, Goodwin P (2010) Prognosis of BRCA-associated breast cancer: a summary of evidence. Breast Cancer Res Treat 119:13–24PubMedCrossRef

33.

Robson M, Lewin D, Federici M, Satagopan J, Bogolminy F, Heerdt A, Borgen P, McCormick B, Hudis C, Norton L, Boyd J, Offit K (1999) Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91:2112–2117PubMedCrossRef

34.

Chappuis PO, Kaputa L, Bégin LR, Wong N, Brunet JS, Narod SA, Slingerland J, Foulkes WD (2000) Germline BRCA1/2 mutations and p27 (Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol 18:4045–4052PubMed

35.

Stoppa-Lyonnet D, Ansquer Y, Dreyfus H, Gautier C, Gauthier-Villars M, Bourstyn E, Clough KB, Magdelenat H, Pouillart P, Vincent-Salomon A, Fourquet A, for the Institute Curie Breast Cancer Group, Asselian B (2000) Familial invasive breast cancer: worse outcome related to BRCA1 mutations. J Clin Oncol 18:4053–4059PubMed

36.

Moller P, Evans DG, Reis MM, Gregory H, Anderson E, Maehle L, Lalloo F, Howell A, Apold J, Clark N, Lucassen A, Steel CM (2007) Surveillance for familial breast cancer: differences in outcome according to BRCA mutation status. Int J Cancer 121:1017–1020PubMedCrossRef

37.

Lee EH, Park SK, Park B, Kim SW, Lee MH, Ahn SH, Son BH, Yoo KY, Kang D (2010) Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat 122:11–25PubMedCrossRef

38.

Cortesi L, Masini C, Cirilli C, Medici V, Marchi I, Cavazzini G, Pasini G, Turchetti D, Federico M (2010) Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer. BMC Cancer 10:90PubMedCrossRef

39.

Lee LJ, Alexander B, Schnitt SJ, Comander A, Gallagher B, Garber JE, Tung N (2011) Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers. Cancer 117:3093–3100PubMedCrossRef

40.

Colleoni M, Cole BF, Viale G, Regan MM, Price KN, Maiorano E, Mastropasqua MG, Crivellari D, Gelber RD, Goldhirsch A, Coates AS, Gusterson BA (2010) Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol 28:2966–2973PubMedCrossRef

41.

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329–2334PubMedCrossRef

42.

Arun B, Bayraktar S, Liu DD, Gutierrez-Barrera AM, Atchley D, Pusztai L, Litton J, Valero V, Meric-Bernstam F, Hortobagyi GN, Albarracin C (2011) Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and non-carriers: a single institution experience. J Clin Oncol (in press)

43.

Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hudis CA, Ellis MJ, Berry DA (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506PubMedCrossRef

44.

Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O’Reilly S, Verrill M, Smith I, Yarnold J et al (2009) Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet 373:1681–1692PubMedCrossRef

45.

Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921PubMedCrossRef

46.

Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly (ADP-ribose) polymerase. Nature 434:913–917PubMedCrossRef

47.

McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O’Connor MJ, Tutt AN, Zdzienicka MZ, Smith GC, Ashworth A (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 66:8109–8115PubMedCrossRef

48.

Abbott DW, Freeman ML, Holt JT (1998) Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 90:978–985PubMedCrossRef

49.

Husain A, He G, Venkatraman ES, Spriggs DR (1998) BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum (II). Cancer Res 58:1120–1123PubMed

50.

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

51.

Ren Q, Potoczek MB, Krajewski S, Krajewska M, Basu A, Haldar S, Reed JC, Turner BC (2001) Transcriptional regulation of the Bcl-2 gene by wild type BRCA1 is important in regulating response to DNA damage-induced apoptosis (abstract). Proc Am Assoc Cancer Res 42:2991

52.

Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, Weber B, Rebbeck T, Neuhausen SL, Ghadirian P, Foulkes WD, Gershoni-Baruch R, Friedman E, Rennert G, Wagner T, Isaacs C, Kim-Sing C, Ainsworth P, Sun P, Narod SA (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case–control study. J Clin Oncol 23:7491–7496PubMedCrossRef

53.

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

54.

Struewing JP, Watson P, Easton DF, Ponder BA, Lynch HT, Tucker MA (1995) Prophylactic oophorectomy in inherited breast/ovarian cancer families. J Natl Cancer Inst Monogr (17):33–35

55.

Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975PubMedCrossRef

56.

Zhang XT, Kang LG, Ding L, Vranic S, Gatalica Z, Wang ZY (2011) A positive feedback loop of ER-alpha36/EGFR promotes malignant growth of ER-negative breast cancer cells. Oncogene 30:770–780PubMedCrossRef

57.

Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, Isaacs C, Evans DG, Lynch H, Eeles RA, Neuhausen SL, Daly MB, Matloff E, Blum JL, Sabbatini P, Barakat RR, Hudis C, Norton L, Offit K, Rebbeck TR (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 26:1331–1337PubMedCrossRef

58.

Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, Tucker MA, Struewing JP, Hartge P (2003) Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 95:1072–1078PubMedCrossRef

Titel: Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations
verfasst von: Soley Bayraktar
Angelica M. Gutierrez-Barrera
Diane Liu
Tunc Tasbas
Ugur Akar
Jennifer K. Litton
E. Lin
Constance T. Albarracin
Funda Meric-Bernstam
Ana M. Gonzalez-Angulo
Gabriel N. Hortobagyi
Banu K. Arun
Publikationsdatum: 01.11.2011
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/s10549-011-1711-z

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations

Abstract

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2011

Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results from a randomized controlled trial

Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer

CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways

The association of reproductive factors and breastfeeding with long term survival from breast cancer

Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial

Absenteeism and short-term disability associated with breast cancer

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

Sind Frauen die fähigeren Ärzte?

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Onkologie