Skip to main content

Advertisement

Log in

Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Molecular subtyping confirms that breast cancer comprises at least four genetically distinct entities based on the expression of specific genes including estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. A comprehensive search for studies examining outcomes after BCT and/or mastectomy according to breast cancer subtype was performed using Medline and cross-referencing available data. Reviews of each study were conducted and data extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. A total of 12,592 breast cancer patients who underwent either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies. Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than both triple-negative (RR 0.38; 95% CI 0.23–0.61); and HER2/neu-overexpressing (RR 0.34; 95% CI 0.26–0.45) tumors following BCT. Luminal tumors were also less likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54–0.89) or triple-negative tumors (OR 0.61; 95% CI 0.46–0.79) after mastectomy. HER2/neu-overexpressing tumors have increased risk of LRR compared to triple-negative tumors (RR 1.44; 95% CI 1.06–1.95) following BCT but there was no difference in LRR between HER2/neu-overexpressing and triple-negative tumors following mastectomy (RR 0.91; 95% CI 0.68–1.22). Luminal tumors exhibit the lowest rates of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors are at increased risk of developing LRR following BCT or mastectomy. Breast cancer subtype should be taken into account when considering local control and identifies those at increased risk of LRR, who may benefit from more aggressive local treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  2. Sørlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874

    Article  PubMed  Google Scholar 

  3. Potti A, Dressman HK, Bild A et al (2006) Genomic signatures to guide the use of chemotherapeutics. Nat Med 12(11):1294–1300

    Article  PubMed  CAS  Google Scholar 

  4. O’Brien KM, Cole SR, Tse CK et al (2010) Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study. Clin Cancer Res 16:6100–6110

    Article  PubMed  Google Scholar 

  5. Spitale A, Mazzola P, Soldini D et al (2009) Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol 20:628–635

    Article  PubMed  CAS  Google Scholar 

  6. 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 randomised trials. Lancet 366:2087–2106

    PubMed  CAS  Google Scholar 

  7. 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 347:1233–1241

    Article  PubMed  Google Scholar 

  8. 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 347:1227–1232

    Article  PubMed  Google Scholar 

  9. Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long term survivors of breast cancer. Breast Cancer Res Treat 107(3):309–330

    Article  PubMed  CAS  Google Scholar 

  10. Riley RD, Abrams KR, Sutton AJ et al (2003) Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future. Br J Cancer 88:1191–1198

    Article  PubMed  CAS  Google Scholar 

  11. Voduc KD, Cheang MC, Tyldesley S et al (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691

    Article  PubMed  Google Scholar 

  12. Arvold ND, Taghian AG, Niemierko A et al (2011) Age, breast cancer subtype approximation and local recurrence after breast conserving therapy. J Clin Oncol 29:3885–3891

    Article  PubMed  Google Scholar 

  13. Millar EK, Graham PH, O’Toole SA et al (2009) Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol 27:4701–4708

    Article  PubMed  Google Scholar 

  14. Wang SL, Li YX, Song YW et al (2010) Triple-negative or HER2-positive status predicts higher rates of locoregional recurrence in node-positive breast cancer patients after mastectomy. Int J Radiat Oncol Biol Phys 80(4):1095–1101

    Article  PubMed  Google Scholar 

  15. Straver ME, Rutgers EJ, Rodenhuis S et al (2010) The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy. Ann Surg Oncol 17:2411–2418

    Article  PubMed  CAS  Google Scholar 

  16. Gabos Z, Thoms J, Ghosh S et al (2010) The association between biological subtype and locoregional recurrence in newly diagnosed breast cancer. Breast Cancer Res Treat 124:187–194

    Article  PubMed  Google Scholar 

  17. Solin LJ, Hwang WT, Vapiwala N (2009) Outcome after breast conservation treatment with radiation for women with triple-negative early-stage invasive breast carcinoma. Clin Breast Cancer 9:96–100

    Article  PubMed  Google Scholar 

  18. Kyndi M, Sørensen FB, Knudsen H et al (2008) Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol 26:1419–1426

    Article  PubMed  CAS  Google Scholar 

  19. Freedman GM, Anderson PR, Li T et al (2009) Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation. Cancer 115:946–951

    Article  PubMed  Google Scholar 

  20. Ihemelandu CU, Naab TJ, Mezghebe HM et al (2008) Treatment and survival outcome for molecular breast cancer subtypes in black women. Ann Surg 247:463–469

    Article  PubMed  Google Scholar 

  21. Haffty BG, Yang Q, Reiss M et al (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652–5657

    Article  PubMed  Google Scholar 

  22. Meyers MO, Klauber-Demore N, Ollila DW et al (2011) Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol 18(10):2851–2857

    Article  PubMed  Google Scholar 

  23. Wong FY, Chin FK, Lee KA, Soong YL, Chua ET (2011) Hormone receptors and HER-2 status as surrogates for breast cancer molecular subtypes prognosticate for disease control in node negative Asian patients treated with breast conservation therapy. Ann Acad Med Singapore 40(2):90–97

    PubMed  Google Scholar 

  24. Siponen ET, Vaalavirta L, Joensuu H, Vironen J, Heikkilä P, Leidenius MH (2011) Ipsilateral breast recurrence after breast conserving surgery in patients with small (≤2 cm) breast cancer treated with modern adjuvant therapies. Eur J Surg Oncol 37(1):25–31

    Article  PubMed  CAS  Google Scholar 

  25. Mersin H, Gülben K, Berberoğlu U et al (2011) Prognostic factors affecting postmastectomy locoregional recurrence in patients with early breast cancer: are intrinsic subtypes effective? World J Surg 35(10):2196–2202

    Article  PubMed  Google Scholar 

  26. Haffty BG, Fischer D, Beinfield M et al (1991) Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 21:293–298

    Article  PubMed  CAS  Google Scholar 

  27. Haffty BG, Reiss M, Beinfield M et al (1996) Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse. J Clin Oncol 14:52–57

    PubMed  CAS  Google Scholar 

  28. Giuliano AE, McCall L, Beitsch P et al (2010) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 252:426–432

    PubMed  Google Scholar 

  29. Dunne C, Burke JP, Morrow M et al (2009) Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol 27:1615–1620

    Article  PubMed  Google Scholar 

  30. NSABP B-39, RTOG 0413 (2006) A randomized phase III study of conventional whole breast irradiation versus partial breast irradiation for women with stage 0, I, or II breast cancer. Clin Adv Hematol Oncol 4:719–721

    Google Scholar 

  31. Livasy CA, Karaca G, Nanda R et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19:264–271

    Article  PubMed  CAS  Google Scholar 

  32. Wolff AC, Hammond ME, Schwartz JN et al. (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145. http://www.asco.org/guidelines/her2

    Google Scholar 

  33. Hammond ME, Hayes DF, Dowsett M et al. (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795. http://www.asco.org/guidelines/erpr

    Google Scholar 

  34. Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple negative breast cancer. N Engl J Med 363:1938–1948

    Article  PubMed  CAS  Google Scholar 

  35. Brenton JD, Carey LA, Ahmed AA et al (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23:7350–7360

    Article  PubMed  CAS  Google Scholar 

  36. Billar JA, Dueck AC, Stucky CC et al (2010) Triple-negative breast cancers: unique clinical presentations and outcomes. Ann Surg Oncol 17(Suppl 3):384–390

    Article  PubMed  Google Scholar 

  37. Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434

    Article  PubMed  Google Scholar 

  38. Recht A, Edge SB, Solin LJ et al (2001) Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1539–1569

    PubMed  CAS  Google Scholar 

  39. Truong PT, Olivotto IA, Kader HA et al (2005) Selecting breast cancer patients with T1–T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 61(5):1337–1347

    Article  PubMed  Google Scholar 

  40. Kunkler IH, Canney P, van Tienhoven G, Russell NS, MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group (2008) Elucidating the role of chest wall irradiation in ‘intermediate-risk’ breast cancer: the MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol) 20:31–34

    Google Scholar 

  41. Abdulkarim BS, Cuartero J, Hanson J et al (2011) Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol 29:2852–2858

    Article  PubMed  Google Scholar 

  42. (EBCTCG) Early Breast Cancer Trialists’ Collaborative Group et al (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  Google Scholar 

  43. Hammond MEH, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 16:2784–2795

    Article  Google Scholar 

  44. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378(9793):771–784

    PubMed  CAS  Google Scholar 

  45. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  PubMed  CAS  Google Scholar 

  46. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 253:1673–1684

    Article  Google Scholar 

  47. Clarke M, Stewart L, Pignon JP et al (1998) Individual patient data meta-analysis in cancer. Br J Cancer 77:2036–2044

    Article  PubMed  CAS  Google Scholar 

  48. Bartelink H, Horiot JC, Poortmans PM et al (2007) Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 25:3259–3265

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karl J. Sweeney.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 54 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lowery, A.J., Kell, M.R., Glynn, R.W. et al. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 133, 831–841 (2012). https://doi.org/10.1007/s10549-011-1891-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-011-1891-6

Keywords

Navigation