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Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer

Received: 23 October 2019     Accepted: 7 December 2019     Published: 31 December 2019
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Abstract

Purpose: To investigate the association between germline deleterious BRCA1 or BRCA2 mutations (gBRCA+) and overall survival (OS) for patients with metastatic triple negative breast cancer (mTNBC). Methods: An IRB approved prospective multisite registry enrolling stage I-IV TNBC patients from 2011-2018 was utilized. Demographics, treatments, genetic results, recurrence and survival were collected. OS was estimated according to the Kaplan-Meier method and compared between groups (gBRCA+and BRCA wild type, wt) by log-rank test. Cox regression model was used for univariate and multivariate analysis of factors associated with risk of death. Results: 100 patients with mTNBC were enrolled on the registry between 2011- 2018. For 100 patients, 20% (20/100) had de novo stage IV whereas 80% (80/100) had metastatic recurrence. 12% had gBRCA+ status; 72% were gBRCA wt type; and 16% had unknown gBRCA status. gBRCA+ patients were younger (49 vs. 57 years, p=0.02) but otherwise well matched to gBRCA wt including similar metastatic disease burden and prior treatments. No patients received a PARP inhibitor. With 31 months median follow-up, median overall survival was 21 months (95% CI [13-23] months) for all patients, 18 months (95% CI [15-27] months) for gBRCA wt patients and has not yet been reached for gBRCA+ patients (p=0.023). 3-year estimated OS is 63% in gBRCA+ versus 28% in gBRCA wt (p=0.02). On multivariate analysis, gBRCA+ was associated with reduced risk of death (HR=0.33; 95%CI [0.23-0.91], p=0.033). Conclusions: In patients with mTNBC gBRCA+ patients have a clinically significantly improved 3-year OS compared to gBRCA wt patients. Further research is needed to understand tumor and host biological reasons for this observation. As these patients are at risk for primary site progression and secondary breast and ovarian cancers, further research regarding the role of proactive surgical treatment in mTNBC with gBRCA mutation is warranted.

Published in Journal of Cancer Treatment and Research (Volume 7, Issue 4)

This article belongs to the Special Issue Modern Multidisciplinary Approach to Management of Stage IV Breast Cancer Patients

DOI 10.11648/j.jctr.20190704.13
Page(s) 81-86
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Breast Cancer, BRCA, Metastatic, Triple Negative

References
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[2] Sharma, P., et al., Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res Treat, 2014. 145 (3): p. 707-14.
[3] Boughey, J. C., et al., Contralateral Prophylactic Mastectomy Consensus Statement from the American Society of Breast Surgeons: Additional Considerations and a Framework for Shared Decision Making. Ann Surg Oncol, 2016. 23 (10): p. 3106-11.
[4] Boughey, J. C., et al., Contralateral Prophylactic Mastectomy (CPM) Consensus Statement from the American Society of Breast Surgeons: Data on CPM Outcomes and Risks. Ann Surg Oncol, 2016. 23 (10): p. 3100-5.
[5] Li, X., et al., Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat, 2017. 161 (2): p. 279-287.
[6] Kassam, F., et al., Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer, 2009. 9 (1): p. 29-33.
[7] Papadimitriou, M., G. Mountzios, and C. A. Papadimitriou, The role of PARP inhibition in triple-negative breast cancer: Unraveling the wide spectrum of synthetic lethality. Cancer Treat Rev, 2018. 67: p. 34-44.
[8] Robson, M., et al., Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med, 2017. 377 (6): p. 523-533.
[9] Hudis, C. A., et al., Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol, 2007. 25 (15): p. 2127-32.
[10] (NCCN), N. C. C. N., Genetic/Familial High RIsk Assessment: Breast and Ovarian Cancer. 2019.
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[12] Gnerlich, J., et al., Surgical removal of the primary tumor increases overall survival in patients with metastatic breast cancer: analysis of the 1988-2003 SEER data. Ann Surg Oncol, 2007. 14 (8): p. 2187-94.
[13] Khan, S. A. and E. S. M. DesJardin, Readdressing the Role of Surgery of the Primary Tumor in de Novo Stage IV Breast Cancer. Cancer Treat Res, 2018. 173: p. 73-88.
[14] Soran, A., et al., Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01. Ann Surg Oncol, 2018. 25 (11): p. 3141-3149.
[15] Blanchard, D. K., et al., Association of surgery with improved survival in stage IV breast cancer patients. Ann Surg, 2008. 247 (5): p. 732-8.
[16] Fields, R. C., et al., Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis. Ann Surg Oncol, 2007. 14 (12): p. 3345-51.
[17] Hazard, H. W., et al., Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer. Cancer, 2008. 113 (8): p. 2011-9.
[18] Metcalfe, K., et al., Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol, 2004. 22 (12): p. 2328-35.
Cite This Article
  • APA Style

    Kelsey E. Larson, Yen Y. Wang, Karissa Finke, Rachel Yoder, Kelsey Schwensen, et al. (2019). Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer. Journal of Cancer Treatment and Research, 7(4), 81-86. https://doi.org/10.11648/j.jctr.20190704.13

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    ACS Style

    Kelsey E. Larson; Yen Y. Wang; Karissa Finke; Rachel Yoder; Kelsey Schwensen, et al. Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer. J. Cancer Treat. Res. 2019, 7(4), 81-86. doi: 10.11648/j.jctr.20190704.13

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    AMA Style

    Kelsey E. Larson, Yen Y. Wang, Karissa Finke, Rachel Yoder, Kelsey Schwensen, et al. Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer. J Cancer Treat Res. 2019;7(4):81-86. doi: 10.11648/j.jctr.20190704.13

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  • @article{10.11648/j.jctr.20190704.13,
      author = {Kelsey E. Larson and Yen Y. Wang and Karissa Finke and Rachel Yoder and Kelsey Schwensen and Anne P. O’Dea and Qamar Khan and Lauren Nye and Jaimie Heldstab and Andrew K. Godwin and Bruce F. Kimler and Priyanka Sharma},
      title = {Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer},
      journal = {Journal of Cancer Treatment and Research},
      volume = {7},
      number = {4},
      pages = {81-86},
      doi = {10.11648/j.jctr.20190704.13},
      url = {https://doi.org/10.11648/j.jctr.20190704.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20190704.13},
      abstract = {Purpose: To investigate the association between germline deleterious BRCA1 or BRCA2 mutations (gBRCA+) and overall survival (OS) for patients with metastatic triple negative breast cancer (mTNBC). Methods: An IRB approved prospective multisite registry enrolling stage I-IV TNBC patients from 2011-2018 was utilized. Demographics, treatments, genetic results, recurrence and survival were collected. OS was estimated according to the Kaplan-Meier method and compared between groups (gBRCA+and BRCA wild type, wt) by log-rank test. Cox regression model was used for univariate and multivariate analysis of factors associated with risk of death. Results: 100 patients with mTNBC were enrolled on the registry between 2011- 2018. For 100 patients, 20% (20/100) had de novo stage IV whereas 80% (80/100) had metastatic recurrence. 12% had gBRCA+ status; 72% were gBRCA wt type; and 16% had unknown gBRCA status. gBRCA+ patients were younger (49 vs. 57 years, p=0.02) but otherwise well matched to gBRCA wt including similar metastatic disease burden and prior treatments. No patients received a PARP inhibitor. With 31 months median follow-up, median overall survival was 21 months (95% CI [13-23] months) for all patients, 18 months (95% CI [15-27] months) for gBRCA wt patients and has not yet been reached for gBRCA+ patients (p=0.023). 3-year estimated OS is 63% in gBRCA+ versus 28% in gBRCA wt (p=0.02). On multivariate analysis, gBRCA+ was associated with reduced risk of death (HR=0.33; 95%CI [0.23-0.91], p=0.033). Conclusions: In patients with mTNBC gBRCA+ patients have a clinically significantly improved 3-year OS compared to gBRCA wt patients. Further research is needed to understand tumor and host biological reasons for this observation. As these patients are at risk for primary site progression and secondary breast and ovarian cancers, further research regarding the role of proactive surgical treatment in mTNBC with gBRCA mutation is warranted.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - Impact of Germline BRCA Mutation Status on Survival in Women with Metastatic Triple Negative Breast Cancer
    AU  - Kelsey E. Larson
    AU  - Yen Y. Wang
    AU  - Karissa Finke
    AU  - Rachel Yoder
    AU  - Kelsey Schwensen
    AU  - Anne P. O’Dea
    AU  - Qamar Khan
    AU  - Lauren Nye
    AU  - Jaimie Heldstab
    AU  - Andrew K. Godwin
    AU  - Bruce F. Kimler
    AU  - Priyanka Sharma
    Y1  - 2019/12/31
    PY  - 2019
    N1  - https://doi.org/10.11648/j.jctr.20190704.13
    DO  - 10.11648/j.jctr.20190704.13
    T2  - Journal of Cancer Treatment and Research
    JF  - Journal of Cancer Treatment and Research
    JO  - Journal of Cancer Treatment and Research
    SP  - 81
    EP  - 86
    PB  - Science Publishing Group
    SN  - 2376-7790
    UR  - https://doi.org/10.11648/j.jctr.20190704.13
    AB  - Purpose: To investigate the association between germline deleterious BRCA1 or BRCA2 mutations (gBRCA+) and overall survival (OS) for patients with metastatic triple negative breast cancer (mTNBC). Methods: An IRB approved prospective multisite registry enrolling stage I-IV TNBC patients from 2011-2018 was utilized. Demographics, treatments, genetic results, recurrence and survival were collected. OS was estimated according to the Kaplan-Meier method and compared between groups (gBRCA+and BRCA wild type, wt) by log-rank test. Cox regression model was used for univariate and multivariate analysis of factors associated with risk of death. Results: 100 patients with mTNBC were enrolled on the registry between 2011- 2018. For 100 patients, 20% (20/100) had de novo stage IV whereas 80% (80/100) had metastatic recurrence. 12% had gBRCA+ status; 72% were gBRCA wt type; and 16% had unknown gBRCA status. gBRCA+ patients were younger (49 vs. 57 years, p=0.02) but otherwise well matched to gBRCA wt including similar metastatic disease burden and prior treatments. No patients received a PARP inhibitor. With 31 months median follow-up, median overall survival was 21 months (95% CI [13-23] months) for all patients, 18 months (95% CI [15-27] months) for gBRCA wt patients and has not yet been reached for gBRCA+ patients (p=0.023). 3-year estimated OS is 63% in gBRCA+ versus 28% in gBRCA wt (p=0.02). On multivariate analysis, gBRCA+ was associated with reduced risk of death (HR=0.33; 95%CI [0.23-0.91], p=0.033). Conclusions: In patients with mTNBC gBRCA+ patients have a clinically significantly improved 3-year OS compared to gBRCA wt patients. Further research is needed to understand tumor and host biological reasons for this observation. As these patients are at risk for primary site progression and secondary breast and ovarian cancers, further research regarding the role of proactive surgical treatment in mTNBC with gBRCA mutation is warranted.
    VL  - 7
    IS  - 4
    ER  - 

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Author Information
  • Department of General Surgery, University of Kansas Medical Center, Kansas City, USA

  • University of Kansas Cancer Center, Kansas City, USA

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

  • University of Kansas Cancer Center, Kansas City, USA

  • University of Kansas Cancer Center, Kansas City, USA

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

  • Department of Pathology & Laboratory Medicine, University of Kansas, Kansas City, USA

  • Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS

  • Department of Internal Medicine, University of Kansas Cancer Center, Westwood, USA

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