Advertisement

Breast Cancer Research and Treatment

, Volume 121, Issue 2, pp 389–398 | Cite as

Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy

  • Lori J. PierceEmail author
  • Kelly-Anne Phillips
  • Kent A. Griffith
  • Saundra Buys
  • David K. Gaffney
  • Meena S. Moran
  • Bruce G. Haffty
  • Merav Ben-David
  • Bella Kaufman
  • Judy E. Garber
  • Sofia D. Merajver
  • Judith Balmaña
  • Amichay Meirovitz
  • Susan M. Domchek
Clinical trial

Abstract

Women with BRCA1 and BRCA2 mutations have an elevated risk of breast cancer and ovarian cancer, but also of developing second primary breast cancer. BRCA1/2 mutation carriers with breast cancer must choose between breast conservation (BCT) and mastectomy (M) yet data on outcomes are limited. The purpose of this study is to compare long-term outcome following BCT and M in BRCA1/2 carriers. 655 women with BRCA1/2 mutations diagnosed with breast cancer and treated with BCT (n = 302) or M (n = 353) were identified and underwent follow-up to assess local, regional, and systemic recurrence. Local failure as first failure was significantly more likely in those treated with BCT compared to M, with a cumulative estimated risk of 23.5 vs. 5.5%, respectively, at 15 years (P < 0.0001); 15-year estimates in carriers treated with BCT and chemotherapy was 11.9% (P = 0.08 when compared to M). Most events appeared to be second primary cancers rather than failure to control the primary tumor. The risk of contralateral breast cancer was high in all groups, exceeding 40%, but was not statistically significantly different by use of adjuvant radiotherapy (RT) or not, suggesting no added risk from scatter RT at 10 and 15 years. There were no differences seen in regional or systemic recurrences between the BCT and M groups, and no difference in overall survival. In conclusion, BRCA1/2 mutation carriers with breast cancer have similar survival whether treated with M or BCT. However, women undergoing BCT have an elevated risk of a second in-breast event that is significantly reduced in the presence of chemotherapy. Contralateral breast cancer events are very common.

Keywords

Hereditary breast cancer BRCA1/2 Breast conservation Mastectomy Radiotherapy 

Notes

Acknowledgments

This research was supported by the Breast Cancer Research Foundation (LJP, SDM); the Colebatch Clinical Research Fellowship of the Cancer Council Victoria (KAP), the National Health and Medical Research Council (NHMRC) of Australia (#145684, 288704, 454508) and grants from the National Breast Cancer Foundation, the NHMRC and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia (kConFab); Susan G. Komen Breast Cancer Foundation (BGH); Dana Farber/Harvard Cancer Center SPORE in Breast Cancer (JEG); and Cancer Genetics Network (HHSN21620074400C) (SMD). We thank follow-up study investigators, research nurses and staff at kConFab and all study sites, the heads and staff of the Australian and New Zealand Family Cancer Clinics, and the families who contribute to kConFab and to this international collaboration.

Conflict of interest statement

No authors have a conflict of interest with the content of this manuscript.

References

  1. 1.
    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 336:1401–1408CrossRefPubMedGoogle Scholar
  2. 2.
    Begg CB, Haile R, Borg A et al (2008) Variation of breast cancer risk amond BRCA1/2 carriers. JAMA 299:194–201CrossRefPubMedGoogle Scholar
  3. 3.
    Fisher B, Anderson S, Bryant J et al (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233–1241CrossRefPubMedGoogle Scholar
  4. 4.
    Veronesi U, Cascinelli N, Mariani L et al (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232CrossRefPubMedGoogle Scholar
  5. 5.
    Mann GJ, Thorne H, Balleine RM et al (2006) Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource. Breast Cancer Res 8:R12CrossRefPubMedGoogle Scholar
  6. 6.
    Phillips KA, Milne RL, Buys S et al (2005) Agreement between self-reported breast cancer treatment and medical records in a population-based breast cancer family registry. J Clin Oncol 23:4679–4686CrossRefPubMedGoogle Scholar
  7. 7.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  8. 8.
    Gooley TA, Leisenring W, Crowley J et al (1999) Estimation of failure probabilities in the presence of competing risks: new representation of old estimators. Stat Med 18:695–706CrossRefPubMedGoogle Scholar
  9. 9.
    Pepe M (1991) Inference for events with dependent risks in multiple endpoints studies. J Am Stat Assoc 86:770–778CrossRefGoogle Scholar
  10. 10.
    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 randomized trials. Lancet 366:2087–2106PubMedGoogle Scholar
  11. 11.
    Schwartz GF, Veronesi U, Clough KB, et al (2006) In: Proceedings on the consensus conference on breast conservation, April 28 to May 2, 2005, Milan, Italy. Cancer 107:242–250Google Scholar
  12. 12.
    Turner BC, Harrold E, Matloff E et al (1999) BRCA1/BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: implications for breast-conserving management in patients with BRCA1/BRCA2 mutations. J Clin Oncol 17:3017–3024PubMedGoogle Scholar
  13. 13.
    Donegan WL, Perez-Mesa CM, Watson FR (1966) A biostatistical study of locally recurrent breast carcinoma. Surg Gynecol Obstet 122:529–540PubMedGoogle Scholar
  14. 14.
    Anderson SJ, Wapnir I, Dignam JJ et al (2009) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol 27:2466–2473CrossRefPubMedGoogle Scholar
  15. 15.
    Wapnir IL, Anderson SJ, Mamounas EP et al (2006) Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 24:2028–2037CrossRefPubMedGoogle Scholar
  16. 16.
    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 32:127–131CrossRefPubMedGoogle Scholar
  17. 17.
    Kauff ND, Domchek SM, Friebel TM et al (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter prospective study. J Clin Oncol 26:1331–1337CrossRefPubMedGoogle Scholar
  18. 18.
    King MC, Wieand S, Hale K et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286:2251–2256CrossRefPubMedGoogle Scholar
  19. 19.
    Bines J, Oleske DM, Cobleigh MA (1996) Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 14:1718–1729PubMedGoogle Scholar
  20. 20.
    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 24:2437–2443CrossRefPubMedGoogle Scholar
  21. 21.
    Verhoog LC, Brekelmans CTM, Seynaeve C et al (1998) Survival and tumour characteristics of breast cancer patients with germline mutations of BRCA1. Lancet 351:316–321CrossRefPubMedGoogle Scholar
  22. 22.
    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 1:65–72CrossRefPubMedGoogle Scholar
  23. 23.
    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 91:2112–2117CrossRefPubMedGoogle Scholar
  24. 24.
    Haffty B, Harold E, Khan A et al (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477CrossRefPubMedGoogle Scholar
  25. 25.
    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 41:2304–2311CrossRefPubMedGoogle Scholar
  26. 26.
    Garcia-Etienne C, Barile M, Gentilini O, et al. Breast-conserving surgery in BRCA1/2 mutation carriers: Are we approaching an answer? Ann Surg Oncol. doi  10.1245/s10434-009-0638-7

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lori J. Pierce
    • 1
    Email author
  • Kelly-Anne Phillips
    • 2
  • Kent A. Griffith
    • 3
  • Saundra Buys
    • 4
  • David K. Gaffney
    • 5
  • Meena S. Moran
    • 6
  • Bruce G. Haffty
    • 7
  • Merav Ben-David
    • 8
  • Bella Kaufman
    • 8
  • Judy E. Garber
    • 9
  • Sofia D. Merajver
    • 10
  • Judith Balmaña
    • 11
  • Amichay Meirovitz
    • 12
  • Susan M. Domchek
    • 13
  1. 1.Department of Radiation OncologyUniversity of Michigan Comprehensive Cancer CenterAnn ArborUSA
  2. 2.Division of Hematology and Medical Oncology, Peter MacCallum Cancer Center and Department of Medicine, St. Vincent’s HospitalThe University of MelbourneMelbourneAustralia
  3. 3.Biostatistics UnitUniversity of Michigan Comprehensive Cancer CenterAnn ArborUSA
  4. 4.Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  5. 5.Department of Radiation Oncology, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  6. 6.Department of Therapeutic Radiology, Yale University School of MedicineNew HavenCTUSA
  7. 7.Department of Radiation OncologyCancer Institute of New Jersey UMDNJ-RWJMSNew BrunswickUSA
  8. 8.Department of Oncology, Sheba Medical CenterTel-Aviv UniversityTel-AvivIsrael
  9. 9.Dana Farber Cancer InstituteHarvard UniversityBostonUSA
  10. 10.Division of Medical Oncology, Department of Internal MedicineUniversity of Michigan Comprehensive Cancer CenterAnn ArborUSA
  11. 11.Servei d’Oncologia Médica, Hospital Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain
  12. 12.Department of OncologyHadassah-Hebrew University Medical CenterJerusalemIsrael
  13. 13.Division of Medical Oncology, Department of Internal Medicine, Abramson Cancer CenterUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations