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Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor
and HR-positive/HER2-negative disease. Unfortunately, it is unclear whether the rate of BCS seen among TNBC patients was related to neoadjuvant chemotherapy use, as this was not reported. However, given the high rates of pathologic complete response seen in TNBC, neoadjuvant chemotherapy use likely is a significant factor.6 It would be helpful to study those who received neoadjuvant chemotherapy separately and investigate differences in BCS rate in that population. In addition, the effect of neoadjuvant hormonal therapy could be investigated and compared with neoadjuvant chemotherapy BCS rates in the subtypes. Although the authors have shown that rates of BCS differ between subtypes, adding to the already accepted biologic differences between the subtypes, the clinical outcomes of BCS in these subtypes, such as disease-free survival and overall survival, were not reported. This study highlighted an inherent bias against BCS in subtypes
with reported local recurrent failures. However, bringing this bias to light may start investigations to identify the cause of the different rates of failure and subsequently to further delineate which patients can safely undergo BCS.
Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor
therapy (BCT). We used our lumpectomy margins database from 2004 to 2006 to predict the effect of these new guidelines on BCT. Methods.dPatients with neoadjuvant therapy, pure ductal carcinoma-in situ, or incomplete margin data were excluded. We applied new (“no ink on tumor”) and old ($2 mm) margin guidelines and compared rates of positive margins, reexcision, and rates of residual disease found at reexcision. Results.dA total of 437 lumpectomy surgeries met the eligibility criteria. Eighty-six percent had invasive ductal carcinoma, 12% invasive lobular carcinoma, and 2% invasive ductal carcinoma and invasive lobular carcinoma. Using a $2 mm margin standard, 36%
Merrill AL, Coopey SB, Tang R, et al (Massachusetts General Hosp, Boston) Ann Surg Oncol 23:729-734, 2016
Background.dThe 2014 guidelines endorsed by Society of Surgical Oncology, the American Society of Breast Surgeons, and the American Society for Radiation Oncology advocate “no ink on tumor” as the new margin requirement for breast-conserving
C. Reyna, MD E. FitzSullivan, MD
References 1. Fisher ER, Anderson S, Redmond C, Fisher B. Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Semin Surg Oncol. 1992;8:161-166. 2. 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.
3. Millar EK, Graham PH, O’Toole SA, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in earlystage invasive breast cancer using a five-biomarker panel. J Clin Oncol. 2009;27:4701-4708. 4. Morrow M. Personalizing extent of breast cancer surgery according to molecular subtypes. Breast. 2013;22: S106-S109. 5. Adkins FC, Gonzalez-Angulo AM, Lei X, et al. Triple-negative breast cancer is not a contraindication for breast conservation. Ann Surg Oncol. 2011;18:3164-3173. 6. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breastconserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014;260: 608-614.
of lumpectomies had positive margins compared to 18% using new guidelines (p < 0.0001). Seventy-seven percent of patients with “ink on tumor” had residual disease found at reexcision. Fifty percent of subjects with margins <2 mm had residual disease (p ¼ 0.0013) but would not have undergone reexcision under the new guidelines. With margins of $2 mm, residual tumor was seen in the shaved margins of 14% of lumpectomies. Residual tumor was more common in reexcisions for ductal carcinoma-in situ <2 mm from a margin than for invasive cancer (53 vs. 40%), although this was not statistically significant. Conclusions.dUse of new lumpectomy margin guidelines would
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
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have reduced reoperation for BCT by half in our patient cohort. However, residual disease was present in many patients who would not have been reexcised with the new guidelines. Longterm follow-up of local recurrence rates is needed to determine if this increase in residual disease is clinically significant. As reported in this article, Merrill and colleagues analyzed the frequency of residual disease in lumpectomies, shave cavity margins, and re-excisions upon the adoption of the new Society of Surgical Oncology/American Society of Radiation Oncology “ink on tumor” guidelines for invasive breast cancer. They compared this frequency with that associated with the prior margin standard of 2 mm or greater, which resulted in a 14% frequency of residual disease being detected. Using the new standard of “ink on tumor,” 77% of re-excisions exhibited residual diseasedhalf of which was ductal carcinoma in situ (DCIS). For the patients with margins smaller than 2 mm but without “ink on tumor,” 50% exhibited residual disease at reexcision, two-thirds of which were DCIS. The new guidelines could reduce re-excision rates by half. In the meta-analysis that established the new guidelines, the local control rate was essentially the same, but nearly all patients had been treated with wholebreast radiation therapy, and the vast majority had received a boost. Why are we hesitant to applaud less surgery for an equal benefit in local control? As the authors noted, the new guidelines apply only to patients with
296
invasive breast cancers who are scheduled for radiation therapy as well as adjuvant therapies, excluding the fast-growing number of low-risk cancers in patients 70 years of age or older who can avoid radiation therapy. Van Zee and colleagues1 noted that in the absence of irradiation, there was no difference in recurrence rates for patients with transected margins (23.3%) and with margins smaller than 2 mm but non-transected (24.7%). For the 25% of all new breast cancer diagnosed as DCIS, recurrence rates increase substantially with a non-transected but smaller-than-2-mm margin width. In a companion study, Merrill and colleagues2 noted that when lumpectomy specimens for DCIS exhibited transected margins, shave cavity margin re-excisions exhibited residual disease in 88% of cases. When a positive margin was defined as 2 mm, 53% of lumpectomies had residual disease in shave cavity margins. Is residual disease, particularly DCIS, just a potential cancer? Sanders and colleagues3 showed very substantial rates of recurrence and metastasis in a group of DCIS patients with low-grade disease treated only by biopsy. Khan and colleagues4 noted that the 10-year risk of local recurrence was 51% with a DCIS margin width of less than 1 mm but 13% with margins equal to or greater than 1 mm in LORIS Trial-equivalent low-risk patients. It is clear that small differences in measured margin width can result in large differences in residual disease in re-excisions and in local recurrence. Although breast irradiation and boost
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
can substantially reduce these events in invasive breast cancer, there remain 35% to 40% of the 60 000 DCIS patients per annum who, at present, can choose not to receive radiation therapy without any significant effect on local control. Faced with the potential morbidities and costs of radiation therapy, these patients might find an additional millimeter a small price to pay for a similar outcome. M. D. Lagios, MD M. J. Silverstein, MD
References 1. 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 breastconserving surgery for 30 years. Ann Surg. 2015;262:623-631. 2. Merrill AL, Tang R, Plichta JK, et al. Should new “no ink on tumor” lumpectomy margin guidelines be applied to ductal carcinoma in situ (DCIS)? A retrospective review using shaved cavity margins. Ann Surg Oncol. 2016;23:3453-3458. 3. Sanders ME, Schuyler PA, Simpson JF, Page DL, Dupont WD. Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up. Mod Pathol. 2015; 28:662-669. 4. Khan S, Epstein M, Lagios MD, Silverstein MJ. Are we overtreating ductal carcinoma in situ (DCIS)? Ann Surg Oncol. 2016; http://dx.doi. org/10.1245/s10434-016-5501z.
with reported local recurrent failures. However, bringing this bias to light may start investigations to identify the cause of the different rates of failure and subsequently to further delineate which patients can safely undergo BCS.
Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor
therapy (BCT). We used our lumpectomy margins database from 2004 to 2006 to predict the effect of these new guidelines on BCT. Methods.dPatients with neoadjuvant therapy, pure ductal carcinoma-in situ, or incomplete margin data were excluded. We applied new (“no ink on tumor”) and old ($2 mm) margin guidelines and compared rates of positive margins, reexcision, and rates of residual disease found at reexcision. Results.dA total of 437 lumpectomy surgeries met the eligibility criteria. Eighty-six percent had invasive ductal carcinoma, 12% invasive lobular carcinoma, and 2% invasive ductal carcinoma and invasive lobular carcinoma. Using a $2 mm margin standard, 36%
Merrill AL, Coopey SB, Tang R, et al (Massachusetts General Hosp, Boston) Ann Surg Oncol 23:729-734, 2016
Background.dThe 2014 guidelines endorsed by Society of Surgical Oncology, the American Society of Breast Surgeons, and the American Society for Radiation Oncology advocate “no ink on tumor” as the new margin requirement for breast-conserving
C. Reyna, MD E. FitzSullivan, MD
References 1. Fisher ER, Anderson S, Redmond C, Fisher B. Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Semin Surg Oncol. 1992;8:161-166. 2. 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.
3. Millar EK, Graham PH, O’Toole SA, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in earlystage invasive breast cancer using a five-biomarker panel. J Clin Oncol. 2009;27:4701-4708. 4. Morrow M. Personalizing extent of breast cancer surgery according to molecular subtypes. Breast. 2013;22: S106-S109. 5. Adkins FC, Gonzalez-Angulo AM, Lei X, et al. Triple-negative breast cancer is not a contraindication for breast conservation. Ann Surg Oncol. 2011;18:3164-3173. 6. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breastconserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014;260: 608-614.
of lumpectomies had positive margins compared to 18% using new guidelines (p < 0.0001). Seventy-seven percent of patients with “ink on tumor” had residual disease found at reexcision. Fifty percent of subjects with margins <2 mm had residual disease (p ¼ 0.0013) but would not have undergone reexcision under the new guidelines. With margins of $2 mm, residual tumor was seen in the shaved margins of 14% of lumpectomies. Residual tumor was more common in reexcisions for ductal carcinoma-in situ <2 mm from a margin than for invasive cancer (53 vs. 40%), although this was not statistically significant. Conclusions.dUse of new lumpectomy margin guidelines would
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
295
have reduced reoperation for BCT by half in our patient cohort. However, residual disease was present in many patients who would not have been reexcised with the new guidelines. Longterm follow-up of local recurrence rates is needed to determine if this increase in residual disease is clinically significant. As reported in this article, Merrill and colleagues analyzed the frequency of residual disease in lumpectomies, shave cavity margins, and re-excisions upon the adoption of the new Society of Surgical Oncology/American Society of Radiation Oncology “ink on tumor” guidelines for invasive breast cancer. They compared this frequency with that associated with the prior margin standard of 2 mm or greater, which resulted in a 14% frequency of residual disease being detected. Using the new standard of “ink on tumor,” 77% of re-excisions exhibited residual diseasedhalf of which was ductal carcinoma in situ (DCIS). For the patients with margins smaller than 2 mm but without “ink on tumor,” 50% exhibited residual disease at reexcision, two-thirds of which were DCIS. The new guidelines could reduce re-excision rates by half. In the meta-analysis that established the new guidelines, the local control rate was essentially the same, but nearly all patients had been treated with wholebreast radiation therapy, and the vast majority had received a boost. Why are we hesitant to applaud less surgery for an equal benefit in local control? As the authors noted, the new guidelines apply only to patients with
296
invasive breast cancers who are scheduled for radiation therapy as well as adjuvant therapies, excluding the fast-growing number of low-risk cancers in patients 70 years of age or older who can avoid radiation therapy. Van Zee and colleagues1 noted that in the absence of irradiation, there was no difference in recurrence rates for patients with transected margins (23.3%) and with margins smaller than 2 mm but non-transected (24.7%). For the 25% of all new breast cancer diagnosed as DCIS, recurrence rates increase substantially with a non-transected but smaller-than-2-mm margin width. In a companion study, Merrill and colleagues2 noted that when lumpectomy specimens for DCIS exhibited transected margins, shave cavity margin re-excisions exhibited residual disease in 88% of cases. When a positive margin was defined as 2 mm, 53% of lumpectomies had residual disease in shave cavity margins. Is residual disease, particularly DCIS, just a potential cancer? Sanders and colleagues3 showed very substantial rates of recurrence and metastasis in a group of DCIS patients with low-grade disease treated only by biopsy. Khan and colleagues4 noted that the 10-year risk of local recurrence was 51% with a DCIS margin width of less than 1 mm but 13% with margins equal to or greater than 1 mm in LORIS Trial-equivalent low-risk patients. It is clear that small differences in measured margin width can result in large differences in residual disease in re-excisions and in local recurrence. Although breast irradiation and boost
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
can substantially reduce these events in invasive breast cancer, there remain 35% to 40% of the 60 000 DCIS patients per annum who, at present, can choose not to receive radiation therapy without any significant effect on local control. Faced with the potential morbidities and costs of radiation therapy, these patients might find an additional millimeter a small price to pay for a similar outcome. M. D. Lagios, MD M. J. Silverstein, MD
References 1. 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 breastconserving surgery for 30 years. Ann Surg. 2015;262:623-631. 2. Merrill AL, Tang R, Plichta JK, et al. Should new “no ink on tumor” lumpectomy margin guidelines be applied to ductal carcinoma in situ (DCIS)? A retrospective review using shaved cavity margins. Ann Surg Oncol. 2016;23:3453-3458. 3. Sanders ME, Schuyler PA, Simpson JF, Page DL, Dupont WD. Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up. Mod Pathol. 2015; 28:662-669. 4. Khan S, Epstein M, Lagios MD, Silverstein MJ. Are we overtreating ductal carcinoma in situ (DCIS)? Ann Surg Oncol. 2016; http://dx.doi. org/10.1245/s10434-016-5501z.