Breast conserving surgery (BCT): Every millimetre counts Joint hospital surgical grand round 15/10/2016

Outline Background Surgical options Adequacy of margin Invasive Ductal Carcinoma (IDC) Ductal Carcinoma In Situ (DCIS)

Breast Cancer Background Most common female cancer Mean age of diagnosis 51.2 11.7% in situ cancers 93.8% ductal type Hong Kong cancer fund statistics Hong Kong Breast Cancer Registry report No. 7 issue 2015 14,400 patients

Surgical options Mastectomy Wide local excision + radiotherapy (BCT)

BCT: Adequacy of margin Invasive ductal carcinoma No ink on tumour At least 2-fold increase risk in positive margins Wider margin widths do not significantly lower risk of ipsilateral breast tumour recurrence (IBTR) Not nullified by histological type, systemic therapy, mode of irradiation Moran MS, Schnitt SJ, Giuliano AE, et al. (2014) 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. J Clin Oncol 32:1507–1515

BCT: Adequacy of margin Ductal carcinoma in situ (DCIS) BCT + whole-breast radiation therapy (WBRT) reduces rate of IBTR 10-year absolute risk reduction 15.2 %1 Non-significant difference in cancer-specific mortality2 1. Correa C, McGale P, Taylor C, et al. (2010) Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010:162–177 2. Narod SA, Iqbal J, Giannakeas V. Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ. JAMA Oncol. 2015 doi: 10.1001/jamaoncol.2015.2510

BCT: Adequacy of margin Ductal carcinoma in situ (DCIS) No consensus on what constitutes adequate margin Re-excision: Complications Discomfort Cosmetics Costs

Pubmed Ductal carcinoma in situ, Breast conserving surgery, Margin Systemic review / meta-analysis 14 results Different conclusions Threshold of 2mm as good as a wider margin1 Margin as wide as possible (greater than 10 mm)2 1. Dunne C, Burke JP, Morrow M. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol. 2009 Apr 2. Wang SY, Chu H, Shamliyan T et el. Network Meta-analysis of Margin Threshold for Women With Ductal Carcinoma In Situ. J Natl Cancer Inst. 2012 Apr

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Consensus guideline 2016 Journal of clinical oncology, 2016 Meta-analysis 20 retrospective studies 7883 DCIS patients 865 IBTR Median follow-up 78.3 months 50 patients with DCIS treated with local excision >4 years follow-up

Guideline recommendations A positive margin, defined as ink on DCIS, is associated with a significant increase in IBTR. This increased risk is not nullified by the use of WBRT. 10-year IBTR rate 24% vs 12% 50% invasive recurrences

Guideline recommendations Margins of at least 2 mm are associated with a reduced risk of IBTR relative to narrower margin widths in patients receiving WBRT. The routine practice of obtaining negative margin widths wider than 2 mm is not supported by the evidence. Statistically significant decrease IBTR for 2mm compared with 0 or 1mm (OR 0.51, P=0.01) No significant differences in IBRT between 2mm, 3 or 5mm and 10mm margins threshold (P>0.40) Marinovich ML, Azizi L, Macaskill P, et al. (in press) The association of surgical margins and local recurrence in women with ductal carcinoma in situ treated with breast-conserving therapy: A meta-analysis. Ann Surg Oncol

2mm Margin width Multi-focal DCIS, with gaps of uninvolved tissue between foci Margin assessment limitations Sampling, ex-vivo specimen, ink tracking Selective re-excision for margins <2mm Factors: (residual calcifications on postexcision mammography, extent of DCIS in proximity to margin, which margin is close [i.e., anterior excised to skin or posterior excised to pectoral fascia v margins associated with residual breast tissue]), cosmetic impact of re-excision, and overall life expectancy

Guideline recommendations Excision without WBRT associated with higher rates of IBTR (26.0% vs 12.0%, P < 0.00001) Inconclusive evidence to suggest lower rate with wider margin than 2mm Van Zee et al (2015): 16% for >10 mm, 23% for between 2.1 and 10 mm 27% for > 0-2 mm 41% for positive margins Other studies: no significant difference Van Zee et al: 16%for margins >10 mm, and increased to 23% for margins between 2.1 and 10 mm, 27% for > 0-2 mm, and 41% for positive margins Other studies (ECOG): no significant difference

Guideline recommendations Endocrine therapy reduced rate of IBTR in patient with positive margin (17.4% vs 11.5%) No evidence to suggest association with margin width Insufficient data to address association of margin width with Patient factors Radiation delivery DCIS with microinvasion

Conclusion Current evidence support adequate margin of 2mm for DCIS undergone BCT with WBRT Selective re-excision for margins <2mm