Skip to main content

Advertisement

SpringerLink
Log in

Loco-Regional Therapy for Early and Advanced Breast Cancer in the Molecular Era

  • Biomarkers (S Dawood, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

The decision of using a treatment modality is essentially based on the benefit it can offer. This can be further refined to identify a subset that stand to benefit the most. This has been successful in planning systemic therapy; unfortunately for loco-regional treatment (LRT) there has been association with numerous risk predictors but no response predictors have been identified. In this review we discuss the evidence of efficacy for LRT based on various risk predictors matched with effective targeted treatment (Hormone therapy and Her2 targeted therapy) and its impact on local control. The largest risk predictors known are the triple negative (TNBC) subset and it is not surprising that postmastectomy radiotherapy has shown a remarkable benefit in TNBC, irrespective of lymph node status. Similarly, one could advocate conservatism in low risk patients who stand to benefit maximum from systemic therapy (ER + ve) and avoid radiotherapy with minimal trade off.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Halsted WS. I. The results of radical operations for the cure of carcinoma of the breast. Ann Surg. 1907;46:1–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  CAS  PubMed  Google Scholar 

  3. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.

    Article  CAS  PubMed  Google Scholar 

  4. Haffty BG, Buchholz TA. Molecular predictors of loco-regional recurrence in breast cancer: ready for prime time? J Clin Oncol. 2010;28:1627–9.

    Article  PubMed  Google Scholar 

  5. Wazer DE. Measuring the value of radiotherapy in older women with breast cancer. J Clin Oncol. 2012;30:2809–11.

    Article  PubMed  Google Scholar 

  6. Albert JM, Liu DD, Shen Y, et al. Nomogram to predict the benefit of radiation for older patients with breast cancer treated with conservative surgery. J Clin Oncol. 2012;30:2837–43.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28:1684–91. Elaborate description of heterogenity of molecular subtypes and resposes.

    Article  PubMed  Google Scholar 

  8. Nguyen PL, Taghian AG, Katz MS, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26:2373–8.

    Article  PubMed  Google Scholar 

  9. Millar EK, Graham PH, O’Toole SA, et al. 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. 2009;27:4701–8.

    Article  PubMed  Google Scholar 

  10. Albert JM, Gonzalez-Angulo AM, Guray M, et al. Estrogen/progesterone receptor negativity and HER2 positivity predict loco-regional recurrence in patients with T1a, bN0 breast cancer. Int J Radiat Oncol Biol Phys. 2010;77:1296–302.

    Article  CAS  PubMed  Google Scholar 

  11. Freedman GM, Anderson PR, Li T, et al. Loco-regional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation. Cancer. 2009;115:946–51.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Fisher B, Anderson S, Bryant J, et al. 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. 2002;347:1233–41.

    Article  PubMed  Google Scholar 

  13. Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on loco-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483–93.

    CAS  PubMed  Google Scholar 

  14. Mamounas EP. NSABP Protocol B-27. Preoperative doxorubicin plus cyclophosphamide followed by preoperative or postoperative docetaxel. Oncology. 1997;11(6 Suppl 6):37–40.

    CAS  PubMed  Google Scholar 

  15. Rausei S, Rovera F, Dionigi G, Tornese D, Fachinetti A, Boni L, et al. Predictors of loco-regional recurrence and cancer-related death after breast cancer surgery. Breast J. 2010;16 Suppl 1:S29–33.

    Article  PubMed  Google Scholar 

  16. Cheng SH, Horng CF, West M. Genomic prediction of loco-regional recurrence after mastectomy in breast cancer. J Clin Oncol. 2006;24:4594–602. Gene expression profiling and breast cancer subtypes and treatment overview of molecular role in risk prediction after mastectomy.

    Article  CAS  PubMed  Google Scholar 

  17. Dent R, Trudeau M, Pritchard KI, et al. Triple negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.

    Article  PubMed  Google Scholar 

  18. Moran M. Should triple-negative breast cancer (TNBC) subtype affect local-regional therapy decision making? ASCO Univ. 2014. Available at: http://meetinglibrary.asco.org/content/11400032-144.

  19. Abdulkarim BS, Cuartero J, Hanson J, et al. Increased risk of loco-regional 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. 2011;29:2852–8. Hypothesis generating study.

  20. Parker CC, Ampil F, Burton G, et al. Is breast conservation therapy a viable option for patients with triple-receptor negative breast cancer? Surgery. 2010;148:386–91.

    Article  PubMed  Google Scholar 

  21. Haffty BG, Yang Q, Reiss M, et al. Loco-regional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006;24:5652–7.

    Article  PubMed  Google Scholar 

  22. Freedman GM, Anderson PR, Li T, et al. Loco-regional recurrence of triple negative breast cancer after breast-conserving surgery and radiation. Cancer. 2009;115:946–51.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Panoff JE, Hurley J, Takita C, et al. Risk of loco-regional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and postmastectomy radiation. Breast Cancer Res Treat. 2011;128:899–906.

    Article  CAS  PubMed  Google Scholar 

  24. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34.

    Article  CAS  PubMed  Google Scholar 

  25. Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23:7265–77.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Wang J, Xie X, Wang X, et al. Loco-regional and distant recurrences after breast conserving therapy in patients with triple-negative breast cancer: a meta-analysis. Surg Oncol. 2013;22:247–55.

    Article  PubMed  Google Scholar 

  28. Lowery A, Kell M, Glynn R, Kerin M, Sweeney K. Loco-regional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133:831–41.

    Article  PubMed  Google Scholar 

  29. Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;10:927–33.

    Article  Google Scholar 

  30. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–75.

    Article  CAS  PubMed  Google Scholar 

  31. Rutgers EJ, Donker M, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial (10981/22023). J Clin Oncol. 2013;31(Suppl); [Abstract LBA1001].

  32. Oliveira M, Cortés J, Bellet M, et al. Management of the axilla in early breast cancer patients in the genomic era. Ann Oncol. 2013;24:1163–70.

    Article  CAS  PubMed  Google Scholar 

  33. Wo JY, Chen K, Neville BA, et al. Effect of very small tumor size on cancer-specific mortality in node-positive breast cancer. J Clin Oncol. 2011;29:2619–27.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Hernandez-Aya LF, Chavez-MacGregor M, Lei X, et al. Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer. J Clin Oncol. 2011;29:2628–34.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Comen EA, Norton L. Breast cancer tumor size, nodal status, and prognosis: biology trumps anatomy. J Clin Oncol. 2011;29:2610–2.

    Article  PubMed  Google Scholar 

  36. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. EBCTCG (Early Breast Cancer Trialists Collaborative Group). Lancet. 2014;383:2127–35.

  37. Kaplan HG, Malmgren JA, Atwood M. T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J. 2009;15:454–60.

    Article  PubMed  Google Scholar 

  38. Kyndi M, Sorensen FB, Knudsen H, et al. 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. 2008;26:1419–26.

    Article  CAS  PubMed  Google Scholar 

  39. Wang J, Shi M, Ling R, et al. Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial. Radiother Oncol. 2011;100:200–4. Randomised study of PMRT in early breast cancer level one evidence.

    Article  CAS  PubMed  Google Scholar 

  40. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74:987–1001.

    Article  PubMed  Google Scholar 

  42. Radiation Therapy Oncology Group. NSABP Protocol B-39/RTOG Protocol 0413: a randomized phase III study of conventional whole breast irradiation (WBI) vs partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer. Available at: www.rtog.org/members/protocols/0413/0413.pdf

  43. Vaidy JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy vs whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014;383:603–13.

    Article  Google Scholar 

  44. Hughe KS, Schnaper AL, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382–7.

    Article  Google Scholar 

  45. Kunkler I, Williams LW, Jack Wet, et al. The PRIME II trial: wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥ 65 years with early breast cancer managed by breast conservation. Abstract #S2-01. Presented at: San Antonio Breast Cancer Symposium: San Antonio; Dec 10–14, 2013

  46. Bouganim N, Tsvetkova E, Clemons M, Amir E. Evolution of sites of recurrence after early breast cancer over the last 20 years: implications for patient care and future research. Breast Cancer Res Treat. 2013;139:603–6.

    Article  CAS  PubMed  Google Scholar 

  47. Mamounas EP, Tang G, Liu Q. The importance of systemic therapy in minimizing local recurrence after BCS: the NSABP experience. J Surg Oncol. 2014;110:45–50.

    Article  PubMed  Google Scholar 

  48. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Anderson SJ, Wapnir I, Dignam JJ, et al. Prognosis after ipsilateral breast tumor recurrence and loco-regional 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. 2009;27:2466–73.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and loco-regional recurrences in five National Surgical Adjuvant Breast and Bowel Project node positive adjuvant breast cancer trials. J Clin Oncol. 2006;24:2028–37.

    Article  PubMed  Google Scholar 

  51. Caudle AS, Yu TK, Tucker SL, et al. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res. 2012;14:R83.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Nita S. Nair and Rajendra A. Badwe declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Surgical Oncology (Breast Service), Tata Memorial Hospital, Dr. E. Borges Marg, Parel, Mumbai, Maharashtra, 400012, India

    Nita S. Nair & Rajendra A. Badwe

Authors
  1. Nita S. Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajendra A. Badwe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nita S. Nair.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nair, N.S., Badwe, R.A. Loco-Regional Therapy for Early and Advanced Breast Cancer in the Molecular Era. Curr Breast Cancer Rep 6, 267–274 (2014). https://doi.org/10.1007/s12609-014-0162-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-014-0162-z

Keywords

Search

Navigation