Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND):
  • As the primary method of axillary staging for patients with early stage breast cancer
• Changes in patient presentation and advancements in systemic therapy:
  • Have led clinicians to question the utility of ALND even in the presence of involved nodes
• The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial:
  • Randomized women with T1 / T2 tumors undergoing breast conservation with one or two positive sentinel nodes to undergo ALND vs. no additional axillary surgery
  • Results showed no difference in local recurrence, disease-free survival (DFS), or overall survival (OS) between the groups
    • The authors concluded that ALND was not indicated in this setting
• One of the major advantages of SLNB compared to ALND:
  • Is the ability to stage the axilla with reduced rates of lymphedema
• A recent meta-analysis of five randomized controlled trials (including the Z0011 trial):
  • Reported a 70% reduction in risk of lymphedema with SLNB compared to ALND
• Multi-gene assays such as the 21-gene recurrence score (RS):
  • Have provided prognostic information regarding risk of distant recurrence:
    • For patients with node-negative, ER+ breast cancers
  • Although evidence suggests that adding chemotherapy to endocrine therapy does result in improved DFS and OS for node-positive patients:
    • Exploratory data suggest that this may not be true for all patients
  • A retrospective analysis of the RS performed on 367 specimens from the SWOG 8814 trial:
    • Showed that RS was prognostic for DFS and OS in node-positive patients
  • The National Comprehensive Cancer Network:
    • Allows patients with 1 to 3 positive nodes to consider the 21-gene recurrence score to determine benefit from chemotherapy
• References
  • Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016; 264(3):413-420.
  • Glechner A, Wockel A, Gartlehner G, et al. Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis. Eur J Cancer. 2013;49(4):812-825.
  • Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, estrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55-65.
  • Breast cancer. National Comprehensive Cancer Network. 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf Accessed September 14, 2018.

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• Several definitions of resectability of pancreatic adenocarcinoma (PDAC) have been approved for determining the possibility for complete clearance (R0 resection) by surgery:
  • Taking into account oncological and general aspects
• Surgical resectability of PDAC is assessed by:
  • The evaluation of local tumor extension to vessels and distant metastases
• Excluding tumor with distant metastases:
  • Which is defined as unresectable with metastases (UR‐M:
• Local resectability is classified in three categories:
  • Resectable (R)
  • Borderline resectable (BR)
  • Unresectable (UR‐LA)
• R PDAC shows:
  • No vascular infiltration to major vessels
  • Complete clearance of R tumor is required in standard pancreatectomy without combined vascular resection
• BR PDAC is sub‐classified into two categories:
  • BR‐PV showing PV distortion or narrowing
  • BR‐A showing semi‐circumferential abutment with a major artery
    • There is a theoretical “borderline” between BR‐PV and BR‐A:
      • Whereas PV resection is currently recommended for achieving R0 resection:
        • Arterial resection remains controversial due to significantly increased rates of morbidity
  • From the surgical perspective, BR‐PV PDAC is borderline resectable:
    • Whereas BR‐A PDAC is borderline unresectable
  • Considering surgical feasibility:
    • R and BR‐PV PDAC should be considered as:
      • Candidates for “PDAC that is planned for resection (potentially resectable PDAC):
        • Potentially resectable PDAC has been treated by upfront surgery, although neoadjuvant for BR PDAC might be considered given the poor oncological outcomes

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• Multiple studies, including a meta-analysis of six studies:
  • Show significant benefit with use of bilateral prophylactic mastectomies (BPM) in BRCA carriers:
    • With up to 90% risk reduction
• The need for axillary staging in the context of prophylactic mastectomy:
  • Pooled results from a meta-analysis and systematic review report similar findings:
    • The risk of occult disease at time of mastectomy:
      • Is low (less than 2%)
    • There is an extremely low risk of nodal involvement:
      • Less than 2%
    • Only 2.8% of cases have a change in management as a result of the SLNB
  • As a result, the routine use of SLNB is not recommended
• Data have evolved that show the benefit of MRI screening in patients at highest risk for breast cancer development
  • McLaughlin and colleagues questioned whether preoperative breast MRI could be used to determine the need for SLNB at time of prophylactic mastectomy:
    • In their series of 178 patients with MRI and SLNB at time of prophylactic mastectomy:
      • Six occult cancers were found
      • All six patients had abnormal findings preoperatively on MRI, with negative predictive value of 100% for invasive disease
        • The researchers concluded that MRI could be utilized to select low-risk patients who may avoid SLNB at time of BPM
  • The study by McLaughlin et al. included BRCA mutation carriers, but only one study specifically evaluated the use of SLNB in BRCA carriers:
    • This trial reported similar results, with occult invasive disease detected in 2.5%
    • No patients in this cohort had node-positive disease, and there were no axillary recurrences at median 34-month followup
• There are case reports of successful SLNB after mastectomy:
  • But currently the routine use is discouraged by the National Comprehensive Cancer Network guidelines
• References
  • Zhou WB, Liu XA, Dai JC, Wang S. Meta-analysis of sentinel lymph node biopsy at the time of prophylactic mastectomy of the breast. Can J Surg 2011;54(5):300-306.
  • Nagaraja V, Edirimanne S, Eslick GD. Is sentinel lymph node biopsy necessary in patients undergoing prophylactic mastectomy? a systematic review and meta-analysis. Breast J. 2016;22(2):158-165.
  • Breast cancer risk reduction. National Comprehensive Cancer Network. Breast Cancer Risk Reduction. Version April 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf. Accessed September 14, 2018
  • McLaughlin SA, Stempel M, Morris EA, Liberman L, King TA. Can magnetic resonance imaging be used to select patients for sentinel lymph node biopsy in prophylactic mastectomy? Cancer. 2008;112(6):1214-1221.
  • Câmara S, Pereira D, André S, et al. The use of sentinel lymph node biopsy in brca1/2 mutation carriers undergoing prophylactic mastectomy: a retrospective consecutive case-series study. Int J Breast Cancer. 2018:1426369
  • Breast cancer. National Comprehensive Cancer Network. 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 14, 2018

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• Neoadjuvant chemotherapy:
  • Does not prolong survival compared to adjuvant chemotherapy:
    • However, it does result in decreased disease burden, and can be beneficial at time of surgery:
      • Providing increased opportunity to perform breast-conserving surgery and reducing need for axillary lymph node dissection
• A meta-analysis of 14 prospective randomized trials of neoadjuvant vs. adjuvant chemotherapy:
  • In 5,500 patients with breast cancer demonstrated that:
    • NAC was associated with an absolute decrease in the mastectomy rate of 16.6% (95% CI 15.1–18.1%)
    • Patients with ER– and HER2 positive breast cancers:
      • Are more likely to experience complete pathologic response than those with ER+ cancers
• Patients with a clinically positive axilla after neoadjuvant chemotherapy:
  • Should undergo axillary dissection at the time of breast surgery
• Patients with no residual adenopathy on clinical exam:
  • May be considered for sentinel lymph node biopsy (SLNB):
    • Accuracy of SLNB after NAC can be improved with:
      • Localization of previously-clipped nodes
      • Use of dual tracer
      • Increasing the number of sentinel nodes retrieved:
        • SLNB after NAC has a false-negative rate of less than 10% only when ≥ 3 sentinel nodes were identified
• References
  • Mieog, JS, van der Hage JA, van de Velde CJ. Neoadjuvant chemotherapy for operable breast cancer. Br J Surg. 2007;94(1):1189-1200.
  • van der Hage JA, van de Velde CJH, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19(22):4224-4237.
  • 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. 1997;15(7):2483-2493.
  • Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678-5685.
  • Boughey JC, Ballman KV, Le-Petross HT, et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance). Ann Surg. 2016;263(4):802-807.
  • Boileau, JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33(3):258-264.

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• According to National Comprehensive Cancer Network (NCCN) guidelines:
  • Risk reducing mastectomy (RRM):
    • Should be routinely discussed with all of the following:
      • BRCA 1
      • BRCA 2
      • Li-Fraumeni syndrome
      • PTEN
      • History of mantle radiation prior to age 30
    • CHEK2 mutations do not require a RRM:
      • There is insufficient evidence in CHEK2 mutations to routinely recommend RRM
• Risk-reducing mastectomy:
  • Has been shown to decrease the incidence of breast cancer by 90% or more in several studies
• References
  • Hartmann LC, Lindor NM. The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med. 2016;374(5):454-468.
  • NCCN Guideline with NCCN Evidence Blocks™ – Breast Cancer Version 3.2019. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed September 21, 2019.
  • Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22(6):1055-1062.
  • Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304(9):967-975.

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• BRCA 1 and BRCA 2 are genes:
  • That produce tumor suppressor proteins:
    • Which help repair damaged DNA
  • They are the most common gene alterations seen in the hereditary breast cancer population
  • They are associated with an increased risk of breast cancer estimated to be:
    • 55% to 70% for BRCA 1 carriers by age 70
    • 45% to 70% in BRCA 2 carriers by age 70
  • While both BRCA 1 and BRCA 2 mutations are associated with an increased risk of breast cancer:
    • BRCA 1 breast cancers more commonly occur in:
      • Younger
      • Premenopausal women
      • Are more likely to be triple negative
  • BRCA 1 is associated with a higher risk of ovarian cancer compared to BRCA 2:
    • With a lifetime risk of 40% to 45% in BRCA 1 carriers compared to 15% to 20% in BRCA 2 carriers
  • BRCA 2 breast cancers more closely resemble the sporadic breast cancer pattern:
    • With a predominance of hormone receptor positive cancers in women greater than 50 years
• CHEK 2 and PALB 2 are moderate penetrance genes:
  • That are less common than BRCA mutations
  • Similar to BRCA 2 deleterious mutations:
    • CHEK 2 and PALB 2 mutations are associated with:
      • Hormone receptor positive postmenopausal breast cancer
• Imaging surveillance for BRCA mutation carriers begins at:
  • Age 25 with annual breast MRI with contrast, with addition of mammography after age 30
  • Although use of screening ultrasound is evolving in women with dense breast tissue:
    • Its use in BRCA carriers has not been defined
• Surveillance strategies have significantly improved early detection but do not prevent breast cancer
• Bilateral salpingo-oophorectomy:
  • Has been shown to provide approximately 50% relative reduction in breast cancer risk:
    • But ultimately prophylactic mastectomy provides the greatest reduction
• The optimal timing of surgery depends on multiple factors, including:
  • The patient’s desire for future breastfeeding
  • Ages of family members at diagnosis
• Several retrospective series and meta-analyses of four prospective studies:
  • Have supported prophylactic mastectomy in BRCA mutation carriers
  • While the data demonstrate a 93% relative risk reduction in breast cancers:
    • They do not demonstrate a survival benefit in this population
• Recent non-randomized studies have evaluated use of nipple-sparing mastectomy (NSM) and demonstrated its feasibility and safety in patients with BRCA mutation:
  • Jakub et al. reported data from 548 risk-reducing NSMs in 346 patients treated at 9 institutions
  • This study included both women opting for prophylactic mastectomies concurrent with treatment for a contralateral breast cancer, and women undergoing bilateral prophylactic mastectomies for risk reduction
  • With median and mean follow up of 34 and 56 months, respectively:      
    • No ipsilateral breast cancers occurred after prophylactic NSM
  • Breast cancer did not develop in any patients undergoing bilateral risk-reducing NSMs
• References
  • Heemskerk-Gerritsen BA, Menke-Pluijmers MB, Jager A, et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis. Ann Oncol. 2013;24(8):2029-2035.
  • Genetic/familial high-risk assessment: breast and ovarian. National Comprehensive Cancer Network. Version 2.2019. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed September 16, 2018.
  • De Felice F, Marchetti C, Musella A, et al. Bilateral risk-reduction mastectomy in BRCA1 and BRCA2 mutation carriers: a meta-analysis. Ann Surg Oncol. 2015;22(9):2876-2880.
  • Ludwig KK, Neuner J, Butler A. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers: a systematic review. Am J Surg. 2016;212(4):660-669
  • Jakub JW, Peled AW, Gray RJ. Oncologic Safety of Prophylactic Nipple-Sparing Mastectomy in a Population With BRCA Mutations: A Multi-institutional Study. JAMA Surg. 2018;153:123-129.
  • Loi M, Desideri I, Olmetto E, Francolini G, Greto D, Bonomo P, et al. BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management. Breast J. 2018;24(6):1019-1023.
  • Peshkin BN, Isaacs, C et al. Overview of hereditary breast and ovarian cancer syndromes. UpToDate website. Updated February 10, 2020. https://www.uptodate.com/contents/genetic-testing-and-management-of-individuals-at-risk-of-hereditary-breast-and-ovarian-cancer-syndromes. Accessed February 15, 2020.
  • Economopoulou P, Dimitriadis G, Psyrri A. Beyond BRCA: new hereditary breast cancer susceptibility genes. Cancer Treat Rev. 2015;41(1):1-8.

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• The standard adequate margin for patients with DCIS treated with breast-conserving surgery followed by whole-breast radiation is:
  • 2 mm
• Negative margins:
  •  Halve the risk of ipsilateral breast tumor recurrence (IBTR) compared with positive margins (defined as ink on DCIS)
• A 2 mm margin minimizes the risk of IBTR relative to narrower negative margin widths:
  • However, larger margins (>2 mm) do not significantly decrease IBTR
• In 2016, margin guidelines related to the treatment of non-invasive breast cancer (e.g., DCIS) in the setting of breast-conservation therapy:
  • Were developed by the Society of Surgical Oncology, American Society for Radiation Oncology, and the American College of Surgeons in a similar manner
  • A consensus statement released by a multidisciplinary panel included:
    • The optimal margins for:
      • Pure DCIS and mixed tumors (invasive and non-invasive components within the same tumor) in the setting of breast conservation
  • Results from the meta-analysis showed:
    • That a 2 mm margin decreases the risk of IBTR in pure DCIS compared to closer negative margins
      • This differs from the previous margin recommendation for invasive cancer:
        • Which remains no ink on tumor:
          • However, in the setting of mixed tumors (invasive cancer with a DCIS component):
            • The recommendation for negative margins remains no ink on tumor, as patients with mixed disease are treated as invasive cancer and therefore receive systemic therapy more often than pure DCIS patients
    • In the setting of DCIS with micro-invasion (no focus of invasive disease larger than 1 mm):
      • The multidisciplinary panel recommends a 2 mm margin:
        • As these lesions have similar rates of IBTR as pure DCIS
• Patients with positive margins after breast-conserving surgery:
  • Should undergo re-excision
• Patients for whom adequate surgical margins cannot be achieved with lumpectomy:
  • Total mastectomy should be performed
• Complete axillary lymph node dissection should not be performed:
  • In the absence of evidence of invasive cancer or proven axillary metastatic disease in women with apparent pure DCIS
  • However, a small proportion of patients with apparent pure DCIS will be found to have invasive cancer at the time of their definitive surgical procedure:
    • Therefore, a sentinel lymph node biopsy should be strongly considered if the patient with apparent pure DCIS is to be treated with mastectomy or with excision in an anatomic location compromising the performance of a future sentinel lymph node procedure
• References
• 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(33):4040-4046.
• Breast cancer. National Comprehensive Cancer Network. 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 9, 2018.

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• Local treatment for ductal carcinoma in situ (DCIS) involves:
  • Mastectomy or breast-conserving therapy, which consists of partial mastectomy followed in most cases by adjuvant radiation therapy
• Sentinel lymph node biopsy (SLNB):
  • Is not indicated for most patients undergoing breast-conserving therapy for DCIS:
    • Because DCIS is a preinvasive lesion:
      • Axillary nodes are rarely involved:
        • Even in cases of extensive multifocal high-grade disease
• If invasive breast cancer is identified after a breast-conserving surgery is performed for DCIS:
  • SLNB can be performed as a second procedure
• If a mastectomy is performed as the initial procedure:
  • A sentinel node biopsy should be performed in the event of an occult invasive cancer
• Radiation therapy alone is not given for DCIS:
  • Although there are ongoing clinical trials comparing active surveillance to surgery with or without endocrine therapy:
    • These are reserved for low- and intermediate-grade DCIS and are not yet considered standard of care
• References
• Virnig BA, Tuttle TM, Shamliyan T, Kane RL. Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst 2010; 102:170.
• Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23(30):7703-7720.
• Intra M, Rotmensz N, Veronesi P, et al. Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European Institute of Oncology on 854 patients in 10 years. Ann Surg. 2008;247(2):315-319.
• Brennan ME, Turner RM, Ciatto S, et al. Ductal carcinoma in situ at core-needle biopsy: meta-analysis of underestimation and predictors of invasive breast cancer. Radiology. 2011;260(1):119-128.
• Youngwirth LM, Boughey JC, Hwang ES. Surgery versus monitoring and endocrine therapy for low-risk DCIS: The COMET Trial. Bull Am Coll Surg. 2017;102(1):62-63.

• Women are candidates for breast-conserving therapy:
  • If the tumor is small enough in relation to the size of the breast to permit resection of the tumor with clear margins and an acceptable cosmetic result
• Absolute contraindications to breast-conserving therapy include:
  • Prior radiation therapy to the breast or chest wall
  • Breast cancer early in pregnancy that would necessitate radiation therapy during pregnancy
  • Diffuse suspicious, malignant-appearing micro calcifications
  • Widespread disease that precludes negative margins with a satisfactory cosmetic result
• Retrospective reviews have shown that patients with collagen vascular diseases, specifically scleroderma:
  • Are at increased risk of radiation toxicities, even with modern techniques:
    • Therefore, the presence of scleroderma would be a relative contraindication for breast-conserving surgery
• There have been attempts to allow for breast-conserving surgery for selected patients with multifocal or multicentric disease:
  • Retrospective data suggest that although patients with multifocal or multicentric disease have increased risk of local recurrence and lower disease-free survival:
    • This finding is independent of the type of surgery performed
  • The Alliance Z11102 study:
    • Sought to prospectively determine whether patients with multiple ipsilateral breast cancers could safely undergo breast-conserving surgery
    • Initial report in 2018 showed that breast-conserving surgery:
      • Was feasible in 93% of patients
        • And could be accomplished in one operation in 67%
    • Data regarding local regional recurrence will be forthcoming
• Percutaneous ablation techniques:
  • Such as cryoablation have promising potential for less-invasive management of breast cancer:
    • However, it is not recommended for multicentric disease
  • Large multicenter randomized clinical trials are needed to determine long-term efficacy
• References
• Morrow M, Strom EA, Bassett LW, et al. Standard for breast conservation therapy in the management of invasive breast carcinoma. CA Cancer J Clin. 2002;52(5):277-300.
• Breast cancer. National Comprehensive Cancer Network. 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 9, 2018.
• Zaremba N, Tamkus D, DiCarlo L, Herman J, Martin M, Bumpers HL. The dilemma of breast cancer treatment and existing collagen vascular disease: a case of scleroderma and review of the literature. Breast J. 2016;22(4):451-455.
• Alm El-Din MA, Taghian AG. Breast conservation therapy for patients with locally advanced breast cancer. Semin Radiat Oncol. 2009;19(4):229-235.
• Rosenkranz KM, Ballman K, McCall L, Kubicky C, Cuttino L, Le-Petross H, 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(10):2858-2866.
• Lanza E, Palussiere J, Buy X, et al. Percutaneous image-guided cryoablation of breast cancer: a systematic review. J Vasc Interv Radiol. 2015;26(11):1652-1657.

• The margin width (distance between the edge of the DCIS and the inked margin):
  • Reflects the completeness of excision and is an important determinant of local recurrence in DCIS:
    • Particularly for patients considering omission of radiotherapy after breast-conserving surgery
• In 2016, the Society of Surgical Oncology and American Society of Radiation Oncology:
  • Developed consensus guidelines regarding margins for DCIS
  • These guidelines were based on:
    • A meta-analysis of 22 studies enrolling 4,660 women treated with partial mastectomy and radiation therapy:
      • There was a 64% reduction in local recurrence risk:
        • In patients with negative margins compared to those with positive margins
      • Margin thresholds ≥2 mm were associated with fewer local recurrences
• For patients with positive margins:
  • Either re-excision or mastectomy to achieve negative margins should be performed
• For patients with close margins:
  • Multiple factors should be considered:
    • The volume / extent of DCIS
    • Its distribution throughout a specimen
    • The volume of the excision
    • The volume of DCIS deemed close to the margin (focal or extensive)
  • After review of pathology:
    • Re-excision and / or radiation boost should be performed
• A post-excision mammogram:
  • May be considered to rule out residual suspicious calcifications in the partial mastectomy operative bed for targeting during re-excision, and breast-conservation therapy may be re-attempted
  • If the close margins are extensive:
    • Mastectomy may be indicated
• References
• 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(12):3801-3810.
• Van Zee KJ, Subhedar P, Olcese C, Patil S, Morrow M. Relationship between margin width and recurrence of ductal carcinoma in situ: analysis of 2996 women treated with breast-conserving surgery for 30 years. Ann Surg. 2015;262(4):623-631.

• 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):1615-1620.

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