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Breast Cancer Research and Treatment

, Volume 175, Issue 3, pp 749–754 | Cite as

Risk of ipsilateral breast tumor recurrence in primary invasive breast cancer following breast-conserving surgery with BRCA1 and BRCA2 mutation in China

  • Wei Cao
  • Yuntao Xie
  • Yingjian He
  • Jinfeng Li
  • Tianfeng Wang
  • Zhaoqing Fan
  • Tie Fan
  • Tao OuyangEmail author
Epidemiology
  • 151 Downloads

Abstract

Purpose

BRCA1/2 germline mutations are associated with a high risk of breast cancer, which may preclude mutation carriers from breast-conserving surgery (BCS). This study retrospectively examined whether mutation status influenced the rate of ipsilateral breast tumor recurrence (IBTR) after BCS  in Chinese women.

Methods

Patients who underwent BCS were enrolled in carriers group and non-carriers group according to their BRCA1/2 mutation status in the study. The correlations were analyzed between IBTR incidence and BRCA1/2 mutation. The IBTR cases were further separated into new primary tumor (NP) and true local recurrences (TR). The risk factors of NP were studied in multivariate analysis.

Results

1947 consecutive Chinese women with primary invasive breast cancer were selected. 103 patients were identified as BRCA1/2 mutation carriers and 1844 were non-carriers. BRCA1/2 mutation carriers were younger (P < 0.001) with more often negative HER-2 expression (P = 0.01) and tumor size over 2 cm (P = 0.04) than non-carriers. The median follow-up for all patients was 80 months. The rate of IBTR was 3.9% in mutated carriers and 2.0% in non-carriers, respectively (P = 0.16). In IBTR cases, NP incidence was 3.9% in carrier group and 0.6% in non-carrier group, respectively (P < 0.01). After adjustment of all clinical-pathological factors, BRCA1/2 mutation was the only statistical risk factor of NP incidence (HR = 6.29, P = 0.002), while positive lymph node was nearly statistically significant (HR = 2.70, P = 0.06).

Conclusions

BCS may be a rational option for Chinese BRCA1/2 mutation carriers. High NP incidence in mutation carriers should be paid close attention in the future.

Keywords

Breast cancer Breast-conserving surgery BRCA1/2 mutation Ipsilateral breast tumor recurrence 

Notes

Acknowledgements

The authors would like to acknowledge the staff in Breast Cancer Center Laboratory who performed BRCA mutation screening and built up the BRCA database. We also appreciate the follow-up group of Peking University Cancer Hospital & Institute who offered us part of survival information of patients.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

A broad informed consent was obtained from all individual participants included in the study. But due to the retrospective nature of the study, specified informed consent was waived.

References

  1. 1.
    Fan L, Strasser-Weippl K, Li JJ et al (2014) Breast cancer in China. Lancet Oncol 15(7):e279–e289.  https://doi.org/10.1016/S1470-2045(13)70567-9 CrossRefGoogle Scholar
  2. 2.
    Roy R, Chun J, Powell SN (2011) BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 12(1):68–78.  https://doi.org/10.1038/nrc3181 CrossRefGoogle Scholar
  3. 3.
    Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71CrossRefGoogle Scholar
  4. 4.
    Wooster R, Bignell G, Lancaster J et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378(6559):789–792CrossRefGoogle Scholar
  5. 5.
    Antoniou A, Pharoah PD, Narod S et al (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(5):1117–1130.  https://doi.org/10.1086/375033 CrossRefGoogle Scholar
  6. 6.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333.  https://doi.org/10.1200/JCO.2006.09.1066 CrossRefGoogle Scholar
  7. 7.
    Zhang J, Sun J, Chen J et al (2016) Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer. Breast Cancer Res Treat 158(3):455–462.  https://doi.org/10.1007/s10549-016-3902-0 CrossRefGoogle Scholar
  8. 8.
    Fisher B, Anderson S, Bryant J et al (2002) Twenty-year follow-up of a randomised trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241CrossRefGoogle Scholar
  9. 9.
    Christiansen P, Carstensen SL, Ejlertsen B et al (2018) Breast conserving surgery versus mastectomy: overall and relative survival-a population based study by the Danish Breast Cancer Cooperative Group (DBCG). Acta Oncol 57(1):19–25.  https://doi.org/10.1080/0284186X.2017.1403042 CrossRefGoogle Scholar
  10. 10.
    Lagendijk M, van Maaren MC, Saadatmand S et al (2018) Breast conserving therapy and mastectomy revisited: breast cancer-specific survival and the influence of prognostic factors in 129,692 patients. Int J Cancer 142(1):165–175.  https://doi.org/10.1002/ijc.31034 CrossRefGoogle Scholar
  11. 11.
    Hartmann-Johnsen OJ, Kåresen R, Schlichting E et al (2017) Better survival after breast-conserving therapy compared to mastectomy when axillary node status is positive in early-stage breast cancer: a registry-based follow-up study of 6387 Norwegian women participating in screening, primarily operated between 1998 and 2009. World J Surg Oncol 15(1):118.  https://doi.org/10.1186/s12957-017-1184-6 CrossRefGoogle Scholar
  12. 12.
    Gentilini OD, Cardoso MJ, Poortmans P (2017) Less is more. Breast conservation might be even better than mastectomy in early breast cancer patients. Breast 35:32–33.  https://doi.org/10.1016/j.breast.2017.06.004 CrossRefGoogle Scholar
  13. 13.
    Robson M, Levin D, Federici M et al (1999) Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91(24):2112–2117CrossRefGoogle Scholar
  14. 14.
    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(1):44–51CrossRefGoogle Scholar
  15. 15.
    Kirova YM, Stoppa-Lyonnet D, Savignoni A et al (2005) Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy. Eur J Cancer 41(15):2304–2311CrossRefGoogle Scholar
  16. 16.
    Garcia-Etienne CA, Barile M, Gentilini OD et al (2009) Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer? Ann Surg Oncol 16(12):3380–3387.  https://doi.org/10.1245/s10434-009-0638-7 CrossRefGoogle Scholar
  17. 17.
    Valachis A, Nearchou AD, Lind P et al (2014) Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat 144(3):443–455.  https://doi.org/10.1007/s10549-014-2890-1 CrossRefGoogle Scholar
  18. 18.
    Biglia N, D’Alonzo M, Sgro LG et al (2016) Breast cancer treatment in mutation carriers: surgical treatment. Minerva Ginecol 68(5):548–556Google Scholar
  19. 19.
    Giuliano AE, Ballman KV, McCall L et al (2017) Effect of Axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA 318(10):918–926.  https://doi.org/10.1001/jama.2017.11470 CrossRefGoogle Scholar
  20. 20.
    Zhang J, Pei R, Pang Z et al (2012) Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer. Breast Cancer Res Treat 132(2):421–428.  https://doi.org/10.1007/s10549-011-1596-x CrossRefGoogle Scholar
  21. 21.
    Smith TE, Lee D, Turner BC et al (2000) True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management. Int J Radiat Oncol Biol Phys 48(5):1281–1289CrossRefGoogle Scholar
  22. 22.
    Nilsson MP, Hartman L, Kristoffersson U et al (2014) High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer. Breast Cancer Res Treat 147(3):571–578.  https://doi.org/10.1007/s10549-014-3115-3 CrossRefGoogle Scholar
  23. 23.
    Metcalfe K, Lynch HT, Ghadirian P et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22(12):2328–2335CrossRefGoogle Scholar
  24. 24.
    Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27(35):5887–5892.  https://doi.org/10.1200/JCO.2008.19.9430 CrossRefGoogle Scholar
  25. 25.
    Bernstein JL, Thomas DC, Shore RE et al (2013) Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: a WECARE study report. Eur J Cancer 2013 49(14):2979–2985.  https://doi.org/10.1016/j.ejca.2013.04.028 CrossRefGoogle Scholar
  26. 26.
    Basu NN, Ingham S, Hodson J (2015) Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis. Fam Cancer 14(4):531–538.  https://doi.org/10.1007/s10689-015-9825-9 CrossRefGoogle Scholar
  27. 27.
    van den Broek AJ, van ‘t Veer LJ, Hooning MJ et al (2016) Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers. J Clin Oncol 2016 34(5):409–418.  https://doi.org/10.1200/JCO.2015.62.3942 CrossRefGoogle Scholar
  28. 28.
    Kuchenbaecker KB, Hopper JL, Barnes DR et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416.  https://doi.org/10.1001/jama.2017.7112 CrossRefGoogle Scholar
  29. 29.
    Molina-Montes E, Pérez-Nevot B, Pollán M et al (2014) Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: a systematic review and meta-analysis. Breast 23(6):721–742.  https://doi.org/10.1016/j.breast.2014.10.005 CrossRefGoogle Scholar
  30. 30.
    Yao L, Sun J, Zhang J et al (2016) Breast cancer risk in Chinese women with BRCA1 or BRCA2 mutations. Breast Cancer Res Treat 156(3):441–445.  https://doi.org/10.1007/s10549-016-3766-3 CrossRefGoogle Scholar
  31. 31.
    Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast cancer linkage consortium. Am J Hum Genet 56(1):265–271Google Scholar
  32. 32.
    Struewing JP, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408.  https://doi.org/10.1056/NEJM199705153362001 CrossRefGoogle Scholar
  33. 33.
    Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet 62(3):676–689CrossRefGoogle Scholar
  34. 34.
    Fodor FH, Weston A, Bleiweiss IJ et al (1998) Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 63(1):45–51.  https://doi.org/10.1086/301903 CrossRefGoogle Scholar
  35. 35.
    Narod SA (2002) Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer 2(2):113–123.  https://doi.org/10.1038/nrc726 CrossRefGoogle Scholar
  36. 36.
    Park B, Dowty JG, Ahn C et al (2015) Breast cancer risk for Korean women with germline mutations in BRCA1 and BRCA2. Breast Cancer Res Treat 152(3):659–665.  https://doi.org/10.1007/s10549-015-3495-z CrossRefGoogle Scholar
  37. 37.
    Pierce LJ, Strawderman M, Narod SA et al (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18(19):3360–3369CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Cancer CenterPeking University Cancer Hospital & InstituteBeijingPeople’s Republic of China

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