BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer: Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study

Peter A. Fasching, Sibylle Loibl, Chunling Hu, Steven Hart, Hermela Shimelis, Raymond Moore, Christian Schem, Hans Tesch, Michael Untch, Jörn Hilfrich, Mahdi Rezai, Bernd Gerber, Serban Dan Costa, Jens Uwe Blohmer, Tanja Fehm, Jens Huober, Cornelia Liedtke, Richard M Weinshilboum, Liewei M Wang, James N. IngleVolkmar Müller, Valentina Nekljudova, Karsten E. Weber, Brigitte Rack, Matthias Rübner, Gunter Von Minckwitz, Fergus J Couch

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Abstract

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Original languageEnglish (US)
Pages (from-to)2281-2287
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number22
DOIs
StatePublished - Aug 1 2018

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Triple Negative Breast Neoplasms
Neoadjuvant Therapy
Breast Neoplasms
Mutation
Disease-Free Survival
Drug Therapy
Bevacizumab
Anthracyclines
Odds Ratio

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer : Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study. / Fasching, Peter A.; Loibl, Sibylle; Hu, Chunling; Hart, Steven; Shimelis, Hermela; Moore, Raymond; Schem, Christian; Tesch, Hans; Untch, Michael; Hilfrich, Jörn; Rezai, Mahdi; Gerber, Bernd; Costa, Serban Dan; Blohmer, Jens Uwe; Fehm, Tanja; Huober, Jens; Liedtke, Cornelia; Weinshilboum, Richard M; Wang, Liewei M; Ingle, James N.; Müller, Volkmar; Nekljudova, Valentina; Weber, Karsten E.; Rack, Brigitte; Rübner, Matthias; Von Minckwitz, Gunter; Couch, Fergus J.

In: Journal of Clinical Oncology, Vol. 36, No. 22, 01.08.2018, p. 2281-2287.

Research output: Contribution to journalArticle

Fasching, PA, Loibl, S, Hu, C, Hart, S, Shimelis, H, Moore, R, Schem, C, Tesch, H, Untch, M, Hilfrich, J, Rezai, M, Gerber, B, Costa, SD, Blohmer, JU, Fehm, T, Huober, J, Liedtke, C, Weinshilboum, RM, Wang, LM, Ingle, JN, Müller, V, Nekljudova, V, Weber, KE, Rack, B, Rübner, M, Von Minckwitz, G & Couch, FJ 2018, 'BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer: Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study', Journal of Clinical Oncology, vol. 36, no. 22, pp. 2281-2287. https://doi.org/10.1200/JCO.2017.77.2285
Fasching, Peter A. ; Loibl, Sibylle ; Hu, Chunling ; Hart, Steven ; Shimelis, Hermela ; Moore, Raymond ; Schem, Christian ; Tesch, Hans ; Untch, Michael ; Hilfrich, Jörn ; Rezai, Mahdi ; Gerber, Bernd ; Costa, Serban Dan ; Blohmer, Jens Uwe ; Fehm, Tanja ; Huober, Jens ; Liedtke, Cornelia ; Weinshilboum, Richard M ; Wang, Liewei M ; Ingle, James N. ; Müller, Volkmar ; Nekljudova, Valentina ; Weber, Karsten E. ; Rack, Brigitte ; Rübner, Matthias ; Von Minckwitz, Gunter ; Couch, Fergus J. / BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer : Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 22. pp. 2281-2287.
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title = "BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer: Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study",
abstract = "Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3{\%} of patients with TNBC. Overall, patients with mutations had a pCR rate of 50{\%}, compared with 31.5{\%} in patients without a mutation (odds ratio [OR], 2.17; 95{\%} CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5{\%} for BRCA1/2 mutation carriers and 35.6{\%} for those without mutations (OR, 2.90; 95{\%} CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95{\%} CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95{\%} CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.",
author = "Fasching, {Peter A.} and Sibylle Loibl and Chunling Hu and Steven Hart and Hermela Shimelis and Raymond Moore and Christian Schem and Hans Tesch and Michael Untch and J{\"o}rn Hilfrich and Mahdi Rezai and Bernd Gerber and Costa, {Serban Dan} and Blohmer, {Jens Uwe} and Tanja Fehm and Jens Huober and Cornelia Liedtke and Weinshilboum, {Richard M} and Wang, {Liewei M} and Ingle, {James N.} and Volkmar M{\"u}ller and Valentina Nekljudova and Weber, {Karsten E.} and Brigitte Rack and Matthias R{\"u}bner and {Von Minckwitz}, Gunter and Couch, {Fergus J}",
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TY - JOUR

T1 - BRCA1/2 Mutations and bevacizumab in the neoadjuvant treatment of breast cancer

T2 - Response and prognosis results in patients with triple-negative breast cancer From the geparquinto study

AU - Fasching, Peter A.

AU - Loibl, Sibylle

AU - Hu, Chunling

AU - Hart, Steven

AU - Shimelis, Hermela

AU - Moore, Raymond

AU - Schem, Christian

AU - Tesch, Hans

AU - Untch, Michael

AU - Hilfrich, Jörn

AU - Rezai, Mahdi

AU - Gerber, Bernd

AU - Costa, Serban Dan

AU - Blohmer, Jens Uwe

AU - Fehm, Tanja

AU - Huober, Jens

AU - Liedtke, Cornelia

AU - Weinshilboum, Richard M

AU - Wang, Liewei M

AU - Ingle, James N.

AU - Müller, Volkmar

AU - Nekljudova, Valentina

AU - Weber, Karsten E.

AU - Rack, Brigitte

AU - Rübner, Matthias

AU - Von Minckwitz, Gunter

AU - Couch, Fergus J

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

AB - Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

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U2 - 10.1200/JCO.2017.77.2285

DO - 10.1200/JCO.2017.77.2285

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

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