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

PurposeControversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer.MethodsA multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.ResultsPositive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.ConclusionThe use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

[1]  J. Yarnold,et al.  Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever be safely withheld? , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  Stewart J Anderson,et al.  Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[4]  Wayne Beckham,et al.  A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  H. Feigelson,et al.  Variability in reexcision following breast conservation surgery. , 2012, JAMA.

[6]  N. Wolmark,et al.  Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. , 2004, Journal of the National Cancer Institute.

[7]  P. Macaskill,et al.  The Association of Surgical Margins and Local Recurrence in Women with Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Therapy: A Meta-Analysis , 2014, Annals of Surgical Oncology.

[8]  R Coquard,et al.  Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  B. Haffty,et al.  Lobular carcinoma in situ as a component of breast cancer: the long-term outcome in patients treated with breast-conservation therapy. , 1998, International journal of radiation oncology, biology, physics.

[10]  N. Biglia,et al.  Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). , 2013, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[11]  S. Schnitt,et al.  The relationship between shaved margin and inked margin status in breast excision specimens , 1997, Cancer.

[12]  E. Winer,et al.  Effect of age on breast cancer outcomes in women with human epidermal growth factor receptor 2-positive breast cancer: results from a herceptin adjuvant trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  K. Bland,et al.  A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes. , 1998, Journal of the American College of Surgeons.

[14]  J. Weidhaas,et al.  Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Mathieu,et al.  Outcome in breast molecular subtypes according to nodal status and surgical procedures. , 2013, American journal of surgery.

[16]  Tianyu Li,et al.  Locoregional recurrence of triple‐negative breast cancer after breast‐conserving surgery and radiation , 2009, Cancer.

[17]  A. Rosenberg,et al.  Ten‐year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy , 1995, Cancer.

[18]  D. Costea,et al.  Abstract 24: Role of S100A14 in proliferation and invasion of oral cancer-derived cells , 2012 .

[19]  Laura Cortesi,et al.  Multicenter Surveillance of Women at High Genetic Breast Cancer Risk Using Mammography, Ultrasonography, and Contrast-Enhanced Magnetic Resonance Imaging (the High Breast Cancer Risk Italian 1 Study): Final Results , 2011, Investigative radiology.

[20]  R Peto,et al.  Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials , 2011, The Lancet.

[21]  Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. , 2009, JAMA.

[22]  J. Costantino,et al.  Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  A. Taghian,et al.  Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Christian Carrie,et al.  Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. , 1997 .

[25]  J. Landercasper,et al.  Variability in Reexcision Following Breast Conservation Surgery: McCahill LE, Single RM, Aiello Bowles EJ, et al (Michigan State Univ, Grand Rapids; Univ of Vermont, Burlington; Group Health Res Inst, Seattle, WA; et al) JAMA 307:467-475, 2012§ , 2012 .

[26]  H Putter,et al.  Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: long-term results of European Organisation for Research and Treatment of Cancer studies. , 2006, European journal of cancer.

[27]  Richard Symonds-Tayler,et al.  Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  M. Morrow,et al.  Presence of Lobular Carcinoma In Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy , 2008, Annals of Surgical Oncology.

[29]  Reshma Jagsi,et al.  What is an Adequate Margin for Breast-Conserving Surgery? Surgeon Attitudes and Correlates , 2010, Annals of Surgical Oncology.

[30]  T. Nielsen,et al.  Breast cancer subtypes and the risk of local and regional relapse. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  M. Bertagnolli,et al.  Locoregional Recurrence After Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Adverse Impact of Multifocal Disease and Potential Implications of Dose Escalation , 2013, Annals of Surgical Oncology.

[32]  J. Yarnold,et al.  The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial , 2008, The Lancet. Oncology.

[33]  H. Safaii,et al.  The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer. , 2002, American journal of surgery.

[34]  J R Yarnold,et al.  The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial , 2008, The Lancet.

[35]  M. Morrow,et al.  Effect of Margin Width on Local Recurrence in Triple-Negative Breast Cancer Patients Treated with Breast-Conserving Therapy , 2014, Annals of Surgical Oncology.

[36]  K. Bland,et al.  Optimal surgical treatment of invasive lobular carcinoma of the breast , 1997, Annals of Surgical Oncology.

[37]  L. Livi,et al.  Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[38]  J. Marks,et al.  Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  D. Wazer,et al.  Factors determining outcome for breast-conserving irradiation with margin-directed dose escalation to the tumor bed. , 1998, International journal of radiation oncology, biology, physics.

[40]  S. Schnitt,et al.  Pathologic predictors of early local recurrence in stage I and II breast cancer treated by primary radiation therapy , 1984, Cancer.

[41]  L. Price,et al.  Long‐term follow‐up of a prospective policy of margin‐directed radiation dose escalation in breast‐conserving therapy , 2003, Cancer.

[42]  J Bamford,et al.  Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen. , 2007, Health technology assessment.

[43]  R. Clough,et al.  Breast conservation therapy: the influence of molecular subtype and margins. , 2012, International journal of radiation oncology, biology, physics.

[44]  Barbara L. Smith,et al.  Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  A. Luini,et al.  Influence of Margin Status on Outcomes in Lobular Carcinoma: Experience of the European Institute of Oncology , 2011, Annals of surgery.

[46]  A. Hart,et al.  Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  S. Schnitt,et al.  Pathologic findings on re‐excision of the primary site in breast cancer patients considered for treatment by primary radiation therapy , 1987, Cancer.

[48]  J. Peterse,et al.  Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  J. Deschênes,et al.  Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  Saveli Goldberg,et al.  Current Perceptions Regarding Surgical Margin Status After Breast-Conserving Therapy: Results of a Survey , 2005, Annals of surgery.

[51]  A. Luini,et al.  Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[52]  R. Swaby,et al.  Impact of the radiation boost on outcomes after breast-conserving surgery and radiation. , 2011, International journal of radiation oncology, biology, physics.

[53]  B. Haffty.  Locoregional Recurrence of Triple-negative Breast Cancer After Breast-conserving Surgery and Radiation , 2009 .

[54]  G. Németh,et al.  Electron and High-Dose-Rate Brachytherapy Boost in the Conservative Treatment of Stage I–II Breast Cancer , 2002, Strahlentherapie und Onkologie.

[55]  W. Woodward,et al.  Triple-Negative Breast Cancer Is Not a Contraindication for Breast Conservation , 2011, Annals of Surgical Oncology.

[56]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[57]  David Cameron,et al.  2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial , 2007, The Lancet.

[58]  K. Dewyngaert,et al.  Phase I-II trial of prone accelerated intensity modulated radiation therapy to the breast to optimally spare normal tissue. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[59]  C. Cox,et al.  Surgeon Recommendations and Receipt of Mastectomy for Treatment of Breast Cancer , 2010 .

[60]  R Holland,et al.  The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  Les Irwig,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. , 2010, European journal of cancer.

[62]  R. Gopal.  Age, Breast Cancer Subtype Approximation, and Local Recurrence After Breast-Conserving Therapy: Arvold ND, Taghian AG, Niemierko A, et al (Harvard Med School, Boston, MA; Massachusetts General Hosp, Boston; et al) J Clin Oncol 29:3885-3891, 2011§ , 2012 .

[63]  J. Bellon,et al.  Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  Gabor Jozsef,et al.  Prone vs supine positioning for breast cancer radiotherapy. , 2012, JAMA.

[65]  S. Ward,et al.  Hormonal therapies for early breast cancer: systematic review and economic evaluation. , 2007, Health technology assessment.

[66]  H. Mouridsen,et al.  Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma. , 2004, Cancer.

[67]  C. Hudis,et al.  Favorable prognosis in patients with T1a/T1bN0 triple‐negative breast cancers treated with multimodality therapy , 2012, Cancer.

[68]  H. Bartelink,et al.  Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[69]  N. Sneige,et al.  Clinical implications of margin involvement by pleomorphic lobular carcinoma in situ. , 2011, Archives of pathology & laboratory medicine.

[70]  D. Carter.  Margins of "lumpectomy" for breast cancer. , 1986, Human pathology.

[71]  A. Giuliano,et al.  Breast-conserving therapy for triple-negative breast cancer. , 2014, JAMA surgery.

[72]  M. Morrow,et al.  Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  B Fisher,et al.  Fifteen‐year prognostic discriminants for invasive breast carcinoma , 2001, Cancer.

[74]  B. Haffty,et al.  Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer , 2010 .

[75]  S J Schnitt,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 , 1994, Cancer.

[76]  Greg Yothers,et al.  Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. , 2005, The New England journal of medicine.

[77]  J. Hendriks,et al.  Histologic multifocality of tis, T1–2 breast carcinomas implications for clinical trials of breast‐conserving surgery , 1985, Cancer.

[78]  B. E. F. Isher,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. , 2002 .

[79]  J. Yarnold,et al.  Abstract S4-1: The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results , 2012 .