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Predictors of Residual Tumor in Breast-Conserving Therapy

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Breast-conserving therapy is considered to be the standard treatment for early breast tumors (T1–T2). In up to 82 % of breast-conserving surgery, tumor cells were still found to be present at or near the cut edge of the surgical specimen after surgery. Thus, it is of clinical need to identify tumors at high probability for reexcision in the preoperative setting.

Methods

A total of 686 patients with invasive or in situ breast cancers and primary breast-conserving surgery were included. In 169 cases (24.6 %), breast-conserving therapy was either incomplete or the presence of residual tumor could not be assessed. By univariate analysis, the following parameters were associated with increased probability for reexcision: carcinoma in situ component next to the invasive tumor (p < 0.001), lower age (p = 0.025), premenopausal status (p = 0.033), tumor size (p < 0.001), multifocality (p < 0.001), involved lymph nodes (p = 0.006) and lymphovascular invasion (p < 0.001), differentiation (p = 0.002), and overexpression of the Her2/neu receptor (p = 0.004). The variables with the strongest impact on the reexcision probability in multivariate analyses were tumor size and histology (both p < 0.001), followed by multifocality (p = 0.002) and an accompanying carcinoma in situ (p = 0.004). Lymphovascular invasion (p = 0.016) and age (p = 0.047) also were significantly associated with increased reexcision probability in multivariate analyses. A nomogram for predicting residual tumor in breast-conserving therapy was developed.

Conclusions

The clinical and pathological parameters associated with increased reexcision rates will help to assess an optimized surgical margin, to decrease reexcision rates, and therefore to improve patient care and the quality of life for patients.

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References

  1. Arriagada R, Le MG, Rochard F, Contesso G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol. 1996;14(5):1558–64.

    PubMed  CAS  Google Scholar 

  2. Blichert-Toft M, Rose C, Andersen JA, et al. Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr. 1992(11):19–25.

    PubMed  Google Scholar 

  3. 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(16):1233–41.

    Article  PubMed  Google Scholar 

  4. Jacobson JA, Danforth DN, Cowan KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med. 1995;332(14):907–11.

    Article  PubMed  CAS  Google Scholar 

  5. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst. 2000;92(14):1143–50.

    Article  PubMed  Google Scholar 

  6. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227–32.

    Article  PubMed  Google Scholar 

  7. Cao D, Lin C, Woo SH, Vang R, Tsangaris TN, Argani P. Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for reexcisions. Am J Surg Pathol. 2005;29(12):1625–32.

    Article  PubMed  Google Scholar 

  8. Miller AR, Brandao G, Prihoda TJ, Hill C, Cruz AB Jr, Yeh IT. Positive margins following surgical resection of breast carcinoma: analysis of pathologic correlates. J Surg Oncol. 2004;86(3):134–40.

    Article  PubMed  Google Scholar 

  9. Park CC, Mitsumori M, Nixon A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol. 2000;18(8):1668–75.

    PubMed  CAS  Google Scholar 

  10. Houssami N, Macaskill P, Marinovich ML, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 2010;46(18):3219–32.

    Article  PubMed  Google Scholar 

  11. Dunne C, Burke JP, Morrow M, Kell MR. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol. 2009;27(10):1615–20.

    Article  PubMed  Google Scholar 

  12. Fisher ER, Sass R, Fisher B, Gregorio R, Brown R, Wickerham L. Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity. Cancer. 1986;57(9):1717–24.

    Article  PubMed  CAS  Google Scholar 

  13. Kurtz JM. Factors influencing the risk of local recurrence in the breast. Eur J Cancer. 1992;28(2–3):660–6.

    Article  PubMed  CAS  Google Scholar 

  14. Macmillan RD, Purushotham AD, George WD. Local recurrence after breast-conserving surgery for breast cancer. Br J Surg. 1996;83(2):149–55.

    Article  PubMed  CAS  Google Scholar 

  15. Schnitt SJ, Abner A, Gelman R, et al. The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer. 1994;74(6):1746–51.

    Article  PubMed  CAS  Google Scholar 

  16. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002;184(5):383–93.

    Article  PubMed  Google Scholar 

  17. Burkholder HC, Witherspoon LE, Burns RP, Horn JS, Biderman MD. Breast surgery techniques: preoperative bracketing wire localization by surgeons. Am Surg. 2007;73(6):574–8; discussion 578-9.

    PubMed  Google Scholar 

  18. Saadai P, Moezzi M, Menes T. Preoperative and intraoperative predictors of positive margins after breast-conserving surgery: a retrospective review. Breast Cancer. 2011;18(3):221–5.

    Article  PubMed  Google Scholar 

  19. Chagpar A, Yen T, Sahin A, et al. Intraoperative margin assessment reduces reexcision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery. Am J Surg. 2003;186(4):371–7.

    Article  PubMed  Google Scholar 

  20. Ngo C, Pollet AG, Laperrelle J, et al. Intraoperative ultrasound localization of nonpalpable breast cancers. Ann Surg Oncol. 2007;14(9):2485–9.

    Article  PubMed  Google Scholar 

  21. Janes SE, Stankhe M, Singh S, Isgar B. Systematic cavity shaves reduces close margins and re-excision rates in breast conserving surgery. Breast. 2006;15(3):326–30.

    Article  PubMed  CAS  Google Scholar 

  22. Sobin LG, Wittekind C. TNM classification of malignant tumours, 7th edn. London: Wiley; 2009.

    Google Scholar 

  23. Edge SB, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual, 7th edn. New York: Springer; 2010.

    Google Scholar 

  24. Orucevic A, Chen J, McLoughlin JM, Heidel RE, Panella T, Bell J. Is the TNM staging system for breast cancer still relevant in the era of biomarkers and emerging personalized medicine for breast cancer: an institution’s 10-year experience. Breast J. 2015;21(2):147–54.

    Article  PubMed  Google Scholar 

  25. Wood AM, White IR, Royston P. How should variable selection be performed with multiply imputed data? Stat Med. 2008;27(17):3227–46.

    Article  PubMed  Google Scholar 

  26. van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. J Stat Software. 2011;45(3):1–67.

    Article  Google Scholar 

  27. Rubin DB. Multiple imputation for nonresponse in surveys. London: Wiley; 1987.

    Book  Google Scholar 

  28. Li KH, Meng XL, Raghunathan TE, Rubin DB. Significance levels from repeated p-values with multiply-imputed data. Stat Sinica. 1991;1(1):65–92.

    Google Scholar 

  29. Li KH, Raghunathan TE, Rubin DB. Large-sample significance levels from multiply imputed data using moment-based statistics and an F reference distribution. J Am Stat Assoc. 1991;86(416):1065–73.

    Google Scholar 

  30. Adler W, Lausen B. Bootstrap estimated true and false positive rates and ROC curve. Computat Stat Data Anal. 2009;53(3):718–29.

    Article  Google Scholar 

  31. R: A Language and Environment for Statistical Computing [computer program]. Vienna, Austria: R Foundation for Statistical Computing; 2012.

  32. van Buuren SG-OK. mice: multivariate imputation by chained equations in R. J Stat Software. 2011;45(3):106.

    Article  Google Scholar 

  33. Venables WN, Ripley BD. Modern Applied Statistics with S. New York: Springer; 2002.

    Book  Google Scholar 

  34. Dahl DB. xtable: export tables to LaTeX or HTML. 2012; R package version 1.7-0. http://CRAN.R-project.org/package=xtable.

  35. Sarkar D. Lattice: Multivariate Data Visualization with R. New York: Springer; 2008.

    Book  Google Scholar 

  36. Lesnoff M, Lancelot R. aod: Analysis of overdispersed data. R package version 1.3. http://cran.r-project.org/package=aod 2012.

  37. Potapov S, Adler W, Hofner B, Lausen B. Daim: Diagnostic accuracy of classification models. 2013;R package version 1.1.0.

  38. Aziz D, Rawlinson E, Narod SA, et al. The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer. Breast J. 2006;12(4):331–7.

    Article  PubMed  Google Scholar 

  39. Bani MR, Lux MP, Heusinger K, et al. Factors correlating with reexcision after breast-conserving therapy. Eur J Surg Oncol. 2009;35(1):32–7.

    Article  PubMed  CAS  Google Scholar 

  40. Smitt MC, Horst K. Association of clinical and pathologic variables with lumpectomy surgical margin status after preoperative diagnosis or excisional biopsy of invasive breast cancer. Ann Surg Oncol. 2007;14(3):1040–4.

    Article  PubMed  Google Scholar 

  41. Chagpar AB, Martin RC, 2nd, Hagendoorn LJ, Chao C, McMasters KM. Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique. Am J Surg. 2004;188(4):399–402.

    Article  PubMed  Google Scholar 

  42. Kurniawan ED, Wong MH, Windle I, et al. Predictors of surgical margin status in breast-conserving surgery within a breast screening program. Ann Surg Oncol. 2008;15(9):2542–9.

    Article  PubMed  Google Scholar 

  43. Heil J, Breitkreuz K, Golatta M, et al. Do reexcisions impair aesthetic outcome in breast conservation surgery? Exploratory analysis of a prospective cohort study. Ann Surg Oncol. 2012;19(2):541–7.

    Article  PubMed  Google Scholar 

  44. Advices DM. Inventor. http://www.dunemedical.com.

  45. Allweis TM, Kaufman Z, Lelcuk S, et al. A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery. Am J Surg. 2008;196(4):483–9.

    Article  PubMed  Google Scholar 

  46. Thill M, Roder K, Diedrich K, Dittmer C. Intraoperative assessment of surgical margins during breast conserving surgery of ductal carcinoma in situ by use of radiofrequency spectroscopy. Breast. 20(6):579–80.

  47. Shin HC, Han W, Moon HG, et al. Nomogram for predicting positive resection margins after breast-conserving surgery. Breast Cancer Res Treat. 2012;134(3):1115–23.

    Article  PubMed  Google Scholar 

  48. Pleijhuis RG, Kwast AB, Jansen L, et al. A validated web-based nomogram for predicting positive surgical margins following breast-conserving surgery as a preoperative tool for clinical decision-making. Breast. 2013;22(5):773–9.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors thank the patients of the University Hospital Heidelberg for providing data for this study and Siobhan Fennessy for her support.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany

    Michelle G. Rath MD, Joerg Heil MD, Christoph Domschke MD, Zdravka Roth, Frederik Marme MD, Alexander Scharf MD, Andreas Schneeweiss MD, Christof Sohn MD & Joachim Rom MD

  2. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany

    Lorenz Uhlmann M.Sc. & Meinhard Kieser PhD

  3. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    Hans-Peter Sinn MD

  4. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany

    Frederik Marme MD & Andreas Schneeweiss MD

  5. Department of Gynecology and Obstetrics, Paracelsus Medical University, General Hospital, Nuremberg, Germany

    Michelle G. Rath MD

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  1. Michelle G. Rath MD
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  2. Lorenz Uhlmann M.Sc.
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  3. Joerg Heil MD
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Corresponding author

Correspondence to Joachim Rom MD.

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Rath, M.G., Uhlmann, L., Heil, J. et al. Predictors of Residual Tumor in Breast-Conserving Therapy. Ann Surg Oncol 22 (Suppl 3), 451–458 (2015). https://doi.org/10.1245/s10434-015-4736-4

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  • DOI: https://doi.org/10.1245/s10434-015-4736-4

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