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01-09-2021 | Breast Cancer | Breast Oncology

Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery

Authors: Cindy Cen, MD, Jennifer Chun, MPH, Elianna Kaplowitz, MPH, Deborah Axelrod, MD, Richard Shapiro, MD, Amber Guth, MD, Freya Schnabel, MD

Published in: Annals of Surgical Oncology | Issue 9/2021

Abstract

Background

Neoadjuvant chemotherapy (NAC) has enabled more patients to be eligible for breast-conservation surgery (BCS). Achieving negative lumpectomy margins, however, is challenging due to changes in tissue composition and potentially scattered residual carcinoma in the tumor bed. Data regarding BCS after NAC have shown variable re-excision rates. MarginProbe (Dilon Technologies, Newport News, VA, USA) has been shown to identify positive resection margins intraoperatively and to reduce the number of re-excisions in primary BCS, but has not been studied in NAC+BCS cases. This study aimed to investigate the clinicopathologic characteristics, margin status, and re-excision rates for NAC+BCS patients with and without the use of MarginProbe.

Methods

The Institutional Breast Cancer Database was queried for patients who received NAC and had BCS from 2010 to 2019. The variables of interest were demographics, tumor characteristics, pathologic complete response (pCR), MarginProbe use, and re-excision rates.

Results

The study population consisted of 214 patients who had NAC, 61 (28.5 %) of whom had NAC+BCS. The median age of the patients was 53.5 years. A pCR was achieved for 19 of the patients (31.1 %). Of the remaining 42 patients, 9 (21 %) had close or positive margins that required re-excision. Re-excision was associated with a larger residual tumor size (p = 0.025) and estrogen receptor (ER)-positive disease before NAC (p = 0.041). MarginProbe use was associated with a lower re-excision rate for the patients who had NAC+BCS (6 % vs. 31 %, respectively).

Conclusion

The patients with a larger residual tumor burden and ER-positive disease had a greater risk for inadequate margins at surgery. MarginProbe use was associated with a lower re-excision rate. Techniques to reduce the need for re-excision will support the use of BCS after NAC.

Volders JH, Negenborn VL, Haloua MH, et al. Cosmetic outcome and quality of life are inextricably linked in breast-conserving therapy. J Surg Oncol. 2017;115:941–8. https://doi.org/10.1002/jso.24615.CrossRefPubMed

Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94. https://doi.org/10.1093/jnci/dji021.CrossRefPubMed

Golshan M, Loibl S, Wong SM, et al. Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: surgical results from the BrighTNess randomized clinical trial. JAMA Surg. 2020:e195410. doi:https://doi.org/10.1001/jamasurg.2019.5410.

Rastogi PAS, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRef

Volders JH, Negenborn VL, Spronk PE, et al. Breast-conserving surgery following neoadjuvant therapy-a systematic review on surgical outcomes. Breast Cancer Res Treat. 2018;168:1–12. https://doi.org/10.1007/s10549-017-4598-5.CrossRefPubMed

Tiezzi DG, Andrade JM, Marana HR, Zola FE, Peria FM. Breast-conserving surgery after neoadjuvant therapy for large primary breast cancer. Eur J Surg Oncol. 2008;34:863–7. https://doi.org/10.1016/j.ejso.2008.01.015.CrossRefPubMed

Arlow RL, Paddock LE, Niu X, et al. Breast-conservation therapy after neoadjuvant chemotherapy does not compromise 10-year breast cancer-specific mortality. Am J Clin Oncol. 2018;41:1246–51. https://doi.org/10.1097/coc.0000000000000456.CrossRefPubMedPubMedCentral

Choi J, Laws A, Hu J, Barry W, Golshan M, King T. Margins in breast-conserving surgery after neoadjuvant therapy. Ann Surg Oncol. 2018;25:3541–7. https://doi.org/10.1245/s10434-018-6702-4.CrossRefPubMed

Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy. Cancer. 2005;103:689–95. https://doi.org/10.1002/cncr.20815.CrossRefPubMed

10.

Soucy G, Belanger J, Leblanc G, et al. Surgical margins in breast-conservation operations for invasive carcinoma: Does neoadjuvant chemotherapy have an impact? J Am Coll Surg. 2008;206:1116–21. https://doi.org/10.1016/j.jamcollsurg.2007.12.025.CrossRefPubMed

11.

Volders JH, Haloua MH, Krekel NM, et al. Neoadjuvant chemotherapy in breast-conserving surgery: consequences on margin status and excision volumes: a nationwide pathology study. Eur J Surg Oncol. 2016;42:986–93. https://doi.org/10.1016/j.ejso.2016.02.252.CrossRefPubMed

12.

Isaacs AJ, Gemignani ML, Pusic A, Sedrakyan A. Association of breast-conservation surgery for cancer with 90-day reoperation rates in New York state. JAMA Surg. 2016;151:648–55. https://doi.org/10.1001/jamasurg.2015.5535.CrossRefPubMed

13.

Wang K, Ren Y, He J. Cavity-shaving plus lumpectomy versus lumpectomy alone for patients with breast cancer undergoing breast-conserving surgery: a systematic review and meta-analysis. PLoS One. 2017;12:e0168705. https://doi.org/10.1371/journal.pone.0168705.CrossRefPubMedPubMedCentral

14.

Landercasper J, Borgert AJ, Fayanju OM, et al. Factors associated with reoperation in breast-conserving surgery for cancer: a prospective study of American Society of Breast Surgeon members. Ann Surg Oncol. 2019;26:3321–36. https://doi.org/10.1245/s10434-019-07547-w.CrossRefPubMedPubMedCentral

15.

Havel L, Naik H, Ramirez L, Morrow M, Landercasper J. Impact of the SSO-ASTRO margin guideline on rates of re-excision after lumpectomy for breast cancer: a meta-analysis. Ann Surg Oncol. 2019;26:1238–44. https://doi.org/10.1245/s10434-019-07247-5.CrossRefPubMed

16.

Blohmer JU, Tanko J, Kueper J, Gross J, Volker R, Machleidt A. MarginProbe(c) reduces the rate of re-excision following breast-conserving surgery for breast cancer. Arch Gynecol Obstet. 2016;294:361–7. https://doi.org/10.1007/s00404-016-4011-3.CrossRefPubMed

17.

Schnabel F, Boolbol SK, Gittleman M, et al. A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies. Ann Surg Oncol. 2014;21:1589–95. https://doi.org/10.1245/s10434-014-3602-0.CrossRefPubMedPubMedCentral

18.

Pappo I, Spector R, Schindel A, et al. Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens. J Surg Res. 2010;160:277–81. https://doi.org/10.1016/j.jss.2009.02.025.CrossRefPubMed

19.

Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88:553–64. https://doi.org/10.1016/j.ijrobp.2013.11.012.CrossRefPubMedPubMedCentral

20.

Morrow M, Van Zee KJ, Solin LJ, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. J Clin Oncol. 2016;34:4040–6. https://doi.org/10.1200/JCO.2016.68.3573.CrossRefPubMedPubMedCentral

21.

Bouzon A, Acea B, Garcia A, et al. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy. Cir Esp. 2016;94:379–84. Factores de riesgo de afectacion de los margenes quirurgicos en la cirugia conservadora del cancer de mama tras quimioterapia neoadyuvante. doi:https://doi.org/10.1016/j.ciresp.2016.03.007.

22.

Davoine E, Dion L, Nyangoh Timoh K, et al. Predictive factors associated with involved margins in breast cancer treated with neoadjuvant chemotherapy followed by breast-conserving therapy. J Gynecol Obstet Hum Reprod. 2019;48:467–72. https://doi.org/10.1016/j.jogoh.2019.06.005.CrossRefPubMed

23.

Devane LA, Baban CK, O’Doherty A, Quinn C, McDermott EW, Prichard RS. The impact of neoadjuvant chemotherapy on margin re-excision in breast-conserving surgery. World J Surg. 2020;44(5):1547–51. https://doi.org/10.1007/s00268-020-05383-8.CrossRefPubMed

24.

Sanchez-Munoz A, Plata-Fernandez YM, Fernandez M, et al. The role of immunohistochemistry in breast cancer patients treated with neoadjuvant chemotherapy: an old tool with an enduring prognostic value. Clin Breast Cancer. 2013;13:146–52. https://doi.org/10.1016/j.clbc.2012.11.006.CrossRefPubMed

25.

van Deurzen CH. Predictors of surgical margin following breast-conserving surgery: a large population-based cohort study. Ann Surg Oncol. 2016;23(Suppl 5):627–33. https://doi.org/10.1245/s10434-016-5532-5.CrossRefPubMedPubMedCentral

26.

Wuerstlein R, Harbeck N. Neoadjuvant therapy for HER2-positive breast cancer. Rev Recent Clin Trials. 2017;12:81–92. https://doi.org/10.2174/1574887112666170202165049.CrossRefPubMed

27.

Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. Jul ;15:2483–93. https://doi.org/10.1200/jco.1997.15.7.2483.CrossRefPubMed

28.

Golshan M, Cirrincione CT, Sikov WM, et al. Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II-III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance). Breast Cancer Res Treat. 2016;160:297–304. https://doi.org/10.1007/s10549-016-4006-6.CrossRefPubMedPubMedCentral

29.

Partridge SC, Gibbs JE, Lu Y, Esserman LJ, Sudilovsky D, Hylton NM. Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol. 2002;179:1193–9. https://doi.org/10.2214/ajr.179.5.1791193.CrossRefPubMed

30.

De Los Santos JF, Cantor A, Amos KD, et al. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer (TBCRC 017). Cancer. 2013;119:1776–83. https://doi.org/10.1002/cncr.27995.CrossRefPubMed

31.

Scheel JR, Kim E, Partridge SC, et al. Preoperative MRI, clinical examination, and mammography for residual disease and pathologic complete response after neoadjuvant chemotherapy for breast cancer: ACRIN 6657 Trial. AJR Am J Roentgenol. 2018;210:1376–85. https://doi.org/10.2214/ajr.17.18323.CrossRefPubMedPubMedCentral

32.

Marinovich ML, Macaskill P, Irwig L, et al. Agreement between MRI and pathologic breast tumor size after neoadjuvant chemotherapy, and comparison with alternative tests: individual patient data meta-analysis. BMC Cancer. 2015;15:662. https://doi.org/10.1186/s12885-015-1664-4.CrossRefPubMedPubMedCentral

33.

Thill M. MarginProbe: intraoperative margin assessment during breast-conserving surgery by using radiofrequency spectroscopy. Expert Rev Med Devices. 2013;10:301–15. https://doi.org/10.1586/erd.13.5.CrossRefPubMed

34.

Krekel NM, Haloua MH, Lopes Cardozo AM, et al. Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial. Lancet Oncol. 2013;14:48–54. https://doi.org/10.1016/s1470-2045(12)70527-2.CrossRefPubMed

35.

Schmidt H, Connolly C, Jaffer S, et al. Evaluation of surgically excised breast tissue microstructure using wide-field optical coherence tomography. Breast J. 2019;26(5):917–23. https://doi.org/10.1111/tbj.13663.CrossRefPubMed

36.

Nguyen FT, Zysk AM, Chaney EJ, et al. Intraoperative evaluation of breast tumor margins with optical coherence tomography. Cancer Res. 2009;69:8790–6. https://doi.org/10.1158/0008-5472.can-08-4340.CrossRefPubMedPubMedCentral

37.

Smith BL, Lanahan CR, Specht MC, et al. Feasibility study of a novel protease-activated fluorescent imaging system for real-time, intraoperative detection of residual breast cancer in breast-conserving surgery. Ann Surg Oncol. 2020;27:1854–61. https://doi.org/10.1245/s10434-019-08158-1.CrossRefPubMedPubMedCentral

Title: Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery
Authors: Cindy Cen, MD
Jennifer Chun, MPH
Elianna Kaplowitz, MPH
Deborah Axelrod, MD
Richard Shapiro, MD
Amber Guth, MD
Freya Schnabel, MD
Publication date: 01-09-2021
Publisher: Springer International Publishing
Keywords: Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: Annals of Surgical Oncology / Issue 9/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-020-09524-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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