Bracketing with Multiple Radioactive Seeds to Achieve Negative Margins in Breast Conservation Surgery

Multiple Seeds in Breast Surgery


      • Breast conservation surgery is the treatment of choice for unifocal breast cancer.
      • Breast conservation is less feasible with locally advanced tumors or extensive ductal carcinoma in situ.
      • Radioactive seed localization may allow breast conservation in this population.
      • An approach using multiple radioactive seeds is validated in our study.



      Breast conservation surgery (BCS) is the treatment of choice for unifocal, early-stage breast cancer. The ability to offer BCS to a wider subset of patients, including those with multifocal/multicentric cancer as well as extensive ductal carcinoma in situ, has emerged over time, especially in those undergoing joint oncoplastic reconstruction and those treated with neoadjuvant therapy. However, localization techniques using multiple radioactive seeds for bracketing in this patient subset have not been validated.

      Materials and Methods

      A single-institution retrospective review was conducted of all patients with breast cancer who underwent BCS, guided by multiple bracketed iodine I 125 radioactive seeds between January 2014 and April 2017.


      Bracketing of breast cancer using 2 or more radioactive seeds was performed in 157 breasts in 156 patients. Negative margins were achieved in 124 of 157 (79%) breasts, including 33 cases (21%) that underwent targeted margin reexcision at the time of surgery after intraoperative, multidisciplinary margin assessment. Thirty-three cases (21%) resulted in close or positive margins, of which 11 (7%) and 10 (6.4%) underwent completion mastectomy or repeat lumpectomy, respectively. Twelve patients (7.6%) did not undergo reexcision. En bloc resection was successful in 134 of 157 (85.4%) lumpectomies. Eighty-nine percent of the procedures were coupled with oncoplastic reconstruction.


      Bracketing techniques using multiple radioactive seeds expands the indications for breast conservation therapy in patients who would have traditionally required mastectomy. Intraoperative margin assessment improves surgical and pathologic success. Larger defects created by multifocal resection are optimally managed in concert with oncoplastic reconstruction to minimize asymmetries and aesthetic defects.



      BCS (breast conservation surgery), BCT (breast conservation therapy), DCIS (ductal carcinoma in situ), IDC (invasive ductal carcinoma), ILC (invasive lobular carcinoma), MCBC (multicentric breast cancer), MFBC (multifocal breast cancer), NWL (nonwire localization), pCR (pathologic complete response), WL (wire localization)
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        • NIH consensus conference
        Treatment of early-stage breast cancer.
        JAMA. 1991; 265: 391-395
        • Agarwal S
        • Pappas L
        • Neumayer L
        • et al.
        Effect of breast conservation therapy vs mastectomy on disease-specific survival for early-stage breast cancer.
        JAMA Surg. 2014; 149: 267-274
        • 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: 1233-1241
        • 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: 1227-1232
        • Tan MP
        • Sitoh NY
        • Sim AS.
        Breast conservation treatment for multifocal and multicentric breast cancers in women with small-volume breast tissue.
        ANZ J Surg. 2017; 87 (E5-10)
        • Hall FM
        • Kopans DB
        • Sadowsky NL
        • et al.
        Development of wire localization for occult breast lesions: Boston remembrances.
        Radiology. 2013; 268: 622-627
        • Goudreau SH
        • Joseph JP
        • Seiler SJ.
        Preoperative radioactive seed localization for nonpalpable breast lesions: technique, pitfalls, and solutions.
        Radiographics. 2015; 35: 1319-1334
        • Sung JS
        • King V
        • Thornton CM
        • et al.
        Safety and efficacy of radioactive seed localization with I-125 prior to lumpectomy and/or excisional biopsy.
        Eur J Radiol. 2013; 82: 1453-1457
        • Tran VT
        • David J
        • Patocskai E
        • et al.
        Comparative evaluation of iodine-125 radioactive seed localization and wire localization for resection of breast lesions.
        Can Assoc Radiol J. 2017; 68: 447-455
        • Al-Hilli Z
        • Glazebrook KN
        • McLaughlin SA
        • et al.
        Utilization of multiple I-125 radioactive seeds in the same breast is safe and feasible: a multi-institutional experience.
        Ann Surg Oncol. 2015; 22: 3350-3355
        • Janssen NNY
        • van la Parra RFD
        • Loo CE
        • et al.
        Breast conserving surgery for extensive DCIS using multiple radioactive seeds.
        Eur J Surg Oncol. 2018; 44: 67-73
        • Rosenkranz KM
        • Ballman K
        • McCall L
        • et al.
        The feasibility of breast-conserving surgery for multiple ipsilateral breast cancer: an initial report from ACOSOG Z11102 (Alliance) Trial.
        Ann Surg Oncol. 2018; 25: 2858-2866
        • Giuliano AE
        • Edge SB
        • Hortobagyi GN.
        Eighth edition of the AJCC cancer staging manual: breast cancer.
        Ann Surg Oncol. 2018; 25: 1783-1785
        • Tevis SE
        • Neuman HB
        • Mittendorf EA
        • et al.
        Multidisciplinary intraoperative assessment of breast specimens reduces number of positive margins.
        Ann Surg Oncol. 2018; 25: 2932-2938
        • 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: 553-564
        • 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.
        Ann Surg Oncol. 2016; 23: 3801-3810
        • Murphy BL
        • Boughey JC
        • Keeney MG
        • et al.
        Factors associated with positive margins in women undergoing breast conservation surgery.
        Mayo Clin Proc. 2018; 93: 429-435
        • Keskek M
        • Kothari M
        • Ardehali B
        • et al.
        Factors predisposing to cavity margin positivity following conservation surgery for breast cancer.
        Eur J Surg Oncol. 2004; 30: 1058-1064
        • 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: 2542-2549
        • Barentsz MW
        • Postma EL
        • van Dalen T
        • et al.
        Prediction of positive resection margins in patients with non-palpable breast cancer.
        Eur J Surg Oncol. 2015; 41: 106-112
        • Dryden MJ
        • Dogan BE
        • Fox P
        • et al.
        Imaging factors that influence surgical margins after preoperative 125I radioactive seed localization of breast lesions: comparison with wire localization.
        AJR Am J Roentgenol. 2016; 206: 1112-1118
        • Thomas J
        • Evans A
        • Macartne J
        • et al.
        Radiological and pathological size estimations of pure ductal carcinoma in situ of the breast, specimen handling and the influence on the success of breast conservation surgery: a review of 2564 cases from the Sloane Project.
        Br J Cancer. 2010; 102: 285-293
        • Rauch GM
        • Hobbs BP
        • Kuerer HM
        • et al.
        Microcalcifications in 1657 Patients with pure ductal carcinoma in situ of the breast: correlation with clinical, histopathologic, biologic features, and local recurrence.
        Ann Surg Oncol. 2016; 23: 482-489
        • Benveniste AP
        • Ortiz-Perez T
        • Ebuoma LO
        • et al.
        Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with pure ductal carcinoma in situ (DCIS)?.
        Eur J Radiol. 2017; 96: 74-79
        • Kuerer HM
        • Smith BD
        • Chavez-MacGregor M
        • et al.
        DCIS margins and breast conservation: MD Anderson Cancer Center multidisciplinary practice guidelines and outcomes.
        J Cancer. 2017; 8: 2653-2662
        • Reyna C
        • DeSnyder S.
        Intraoperative margin assessment in breast cancer management.
        Surg Oncol Clin N Am. 2018; 27: 155-165
        • Tran-Harding K
        • Shi Q
        • Gibbs R
        • et al.
        Evaluation of margin status of a breast lumpectomy specimen: what the radiologist should know.
        Curr Probl Diagn Radiol. 2019; 48: 599-604
        • Landercasper J
        • Attai D
        • Atisha D.
        Toolbox to reduce lumpectomy reoperations and improve cosmetic outcome in breast cancer patients: the American Society of Breast Surgeons consensus conference.
        Ann Surg Oncol. 2015; 22: 3174-3183
        • Carter SA
        • Lyons GR
        • Kuerer HM
        • et al.
        Operative and oncologic outcomes in 9861 patients with operable breast cancer: single-institution analysis of breast conservation with oncoplastic reconstruction.
        Ann Surg Oncol. 2016; 23: 3190-3198
        • Mukhtar RA
        • Wong J
        • Piper M
        • et al.
        Breast conservation and negative margins in invasive lobular carcinoma: the impact of oncoplastic surgery and shave margins in 358 patients.
        Ann Surg Oncol. 2018; 25: 3165-3170
        • Velazco CS
        • Wasif N
        • Pockaj BA
        • et al.
        Radioactive seed localization for breast conservation surgery: low positive margin rate with no learning curve.
        Am J Surg. 2017; 214: 1091-1093
        • Wang GL
        • Tsikouras P
        • Zuo HQ
        • et al.
        Radioactive seed localization and wire guided localization in breast cancer: a systematic review and meta-analysis.
        J BUON. 2019; 24: 48-60
        • Tayeh S
        • Gera R
        • Perry N
        • et al.
        The use of magnetic seeds and radiofrequency identifier tags in breast surgery for non-palpable lesions.
        Anticancer Res. 2020; 40: 315-321
        • Mango V
        • Ha R
        • Gomberawalla A
        • et al.
        Evaluation of the SAVI SCOUT surgical guidance system for localization and excision of nonpalpable breast lesions: a feasibility study.
        AJR Am J Roentgenol. 2016; 207: W69-W72
        • Zacharioudakis K
        • Down S
        • Bholah Z
        • et al.
        Is the future magnetic? Magseed localisation for non palpable breast cancer: a multi-centre non randomised control study.
        Eur J Surg Oncol. 2019; 45: 2016-2021
        • Srour MK
        • Kim S
        • Amersi F
        • et al.
        Comparison of wire localization, radioactive seed, and Savi Scout® radar for management of surgical breast disease.
        Breast J. 2020; 26: 406-413