What are Adequate Margins of Resection for Breast-Conserving Therapy?

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1 What are Adequate Margins of Resection for Breast-Conserving Therapy? Jay R. Harris Dana-Farber Cancer Institute (DFCI) Brigham and Women s Hospital (BWH) Harvard Medical School

2 What are Adequate Margins of Resection for Breast-Conserving Therapy? Note that this is just for Invasive Cancer DCIS will be considered separately

3 Disclosures I have no COI disclosures

4 Current Results with BCT Our results from DF/BWCC and MGH are illustrative of the current excellent results seen with BCT Our initial cohort of BCT had a 5- year LR rate of 10% and now it is about 2% * Ref: Arvold N et al JCO 2011

5 Reasons for Excellent Outcomes Better imaging with mammography (not MRI); use of MRI controversial Better evaluation of the resected breast specimens, especially margins Use of systemic therapy (ST), which greatly improves results of RT

6 10-Year LR in NSABP Trials (Ref: Anderson SJ et al. JCO 2005, 27: 2466) Trial ER Status 10-Year LR (%) B-13 No Chemo B-13 Chemo B-14 No Tamoxifen B-14 Tamoxifen B-19 Chemo B-20 Tam +/- Chemo B-23 Chemo - 4.3

7 Adequate Margins of Resection The Boards answer has been 2 mm However, in the context of highly effective systemic therapy and detailed path/mammo evaluation, the current evidence indicates that no ink on tumor is sufficient for the large majority of patients Ref: Morrow M, Harris JR, Schnitt SJ NEJM 2012, 367: 79

8 Joint SSO-ASTRO Consensus on Margins in Invasive Breast Cancer Co-chairs: Monica Morrow SSO Meena Moran ASTRO Participants: ASBS Suzanne Klimberg ASCO Marina Chavez MacGregor ASTRO Gary Freedman, Janet Horton, Jay Harris CAP Stuart Schnitt SSO Armando Giuliano, Seema Khan Advocate Peggy Johnson Methodologist Nehmat Houssami Ref: Annals Surg Oncology, IJROBP, J Clin Oncol, 2014

9 Why a Consensus Conference Now? Wide variation in adequate margins Re-excisions increase costs, lessen the cosmetic outcome, and increase use of mastectomy Recognition of the importance of biology and the impact of systemic therapy on local therapy outcome

10 What Is an Adequate Margin? Case: 60-year-old, 0.8cm invasive cancer ER-, PR-, HER2- What negative margin width precludes the need for re-excision? n = 318 surgeons Not touching > 1-2 mm > 5 mm > 10 mm 11.2% 42.0% 27.9% 18.9% Ref: Azu M, Ann Surg Oncol 2010;17:558

11 What Is an Adequate Margin? 50% Not on ink > 2 mm > 5 mm > 1 cm Ref: Taghian A, Ann Surg 2005;241:629

12 Morrow M, JAMA 2009;302:1551 McCahill L, JAMA 2012;307:467 Rates of Re-excision Wide variation, 6-49% Morrow et al. n = 800 Population-based sample Stage I+II: Re-excision rate 19% McCahill et al. n = 2200 Large convenience sample Re-excision rate 23% 48% of re-excisions done for (-) margins

13 Consensus Conference 2-day meeting in Chicago in 7/13 Stu Schnitt presentation on pathology Review of the pertinent literature Review of updated meta-analysis Consensus development and later expert review by SSO and ASTRO

14 Technical and Methodologic Issues The pancake phenomenon Problems with inking No uniform sampling method Sampling error: even Total Sequential Embedding examines 0.2% of the specimen surface

15 Tumor Tumor Deeper level of same tissue block 2mm <1mm

16 SSO-ASTRO Consensus Updated Meta-analysis Meta-analysis of 33 studies: 28,162 patients 1,506 local recurrences Study eligibility: > 90% Stage I+II Patient age FU > 4 yrs LR related to margin status Whole breast RT

17 # subjects/study 701 Median first yr recruitment Median final yr recruitment Median age Stage: Characteristics of Studies 1984 ( ) 1996 ( ) 53 yrs I/II 55%/45% Tumor size (median) in Meta-analysis 1.6 cm Node positive 26%

18 Characteristics of Studies in Meta-analysis Variable Re-excision 48% Any systemic Rx 40% Chemotherapy 26% Endocrine Rx 38% Median WBRT dose 47.2 Gy Boost 96% Median boost dose 10 Gy

19 Margins Meta-analysis: Results Margins and LR adjusted for follow-up OR 95% CI p-value Margin status Negative 1.0 <.001 Positive/Close Adjusting for age, year of recruitment, endocrine rx did not change results

20 Consensus Statement A positive margin, defined as ink on invasive cancer or DCIS, is associated with at least a 2-fold increase in local recurrence

21 Meta-analysis Results Relationship Between LR and Threshold Margin Distance (MD) MD (mm) # studies # subjects/# LRs / OR* 95% CI / / P association 0.90 P trend 0.58 * Adjusted for f/u

22 Impact of Margin Width on LR: Selected Covariates Covariate # studies Margin Width: OR* 1mm 2mm 5mm p- value Age Endocrine Rx Boost * Adjusted for follow-up

23 Consensus Statement Negative margins (no ink on tumor) optimize local control Wider margin widths do not significantly improve local control The routine practice of obtaining margins more widely clear than no tumor on ink is not indicated

24 IBTR by Year of Recruitment

25 Limitations of the Study Retrospective data subject to selection bias; namely, patient with close margins were selected for no re-excision Lack of patient-level data Older data (at this time)

26 Use of Margins The key concept is that we use margins (and detailed mammo) not to insure there is no cancer remaining, but to insure that there is only limited residual cancer, capable of being eradicated with usual doses of RT systemic therapy Ref: Morrow M, Harris JR, Schnitt SJ NEJM 2012, 367: 79

27 Factors to be Considered in Re-excision Favors Re-excision Favors No Re-excision Tumor close Broad front Focal Foci close Multiple Unifocal EIC Positive Negative Age Younger Older Subtype Non-luminal Luminal

28 Adequate Margins of Resection The Boards answer has been 2 mm However, in the context of highly effective systemic therapy and detailed path/mammo evaluation, the current evidence indicates that no ink on tumor is sufficient for the large majority of patients