As reported in the Journal of Clinical Oncology,1 ASCO has endorsed the recently published Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer.2 The endorsement, with minor qualifications, was made after ASCO Clinical Practice Guidelines Committee staff reviewed the SSO/ASTRO guideline for developmental rigor and an ad hoc review panel reviewed the guideline content.
The panel was co-chaired by Thomas A. Buchholz, MD, of The University of Texas MD Anderson Cancer Center, Houston, (see commentary by Dr. Buchholz on page 76), and Lisa A. Newman, MD, MPH, of the University of Michigan Comprehensive Cancer Center, Ann Arbor.
The primary recommendation of the SSO/ASTRO guideline is that the use of “no ink on tumor” (ie, no cancer cells adjacent to any inked edge/surface of the specimen) is the standard for adequate surgical margin in invasive cancer in the era of multidisciplinary therapy. This margin criterion is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and reduce health-care costs.
The ASCO review panel agreed “that the recommendations are clear, thorough, and based on the most relevant scientific evidence in the area and that they present options acceptable to patients.” The SSO/ASTRO clinical questions and recommendations and ASCO qualifying comments are summarized below.
SSO/ASTRO Recommendations
What is the absolute increase in risk of ipsilateral breast tumor recurrence with a positive margin? Can the use of radiation boost, systemic therapy, or favorable tumor biology mitigate this increased risk?
Recommendation: Positive margins, defined as ink on invasive cancer or ductal carcinoma in situ, are associated with at least a twofold increase in ipsilateral breast tumor recurrence. This increased risk is not eliminated by delivery of radiation boost, systemic therapy, or favorable biology.
Do margin widths wider than no ink on tumor cells reduce the risk of ipsilateral breast tumor recurrence?
Recommendation: Negative margins (no ink on tumor) optimize ipsilateral breast tumor recurrence. Wider margin widths do not significantly lower this risk.
What are the effects of endocrine or biologically targeted therapy or systemic chemotherapy on ipsilateral breast tumor recurrence? Should a patient who is not receiving any systemic treatment have wider margin widths?
Recommendation: Rates of ipsilateral breast tumor recurrence are reduced with the use of systemic therapy. There is no evidence suggesting that margins wider than no ink on tumor are needed in the rare case of a patient not receiving adjuvant systemic therapy.
Should unfavorable biologic subtypes (such as triple-negative breast cancers) require wider margins (than no ink on tumor)?
Recommendation: Margins wider than no ink on tumor are not indicated based on biologic subtype.
Should margin width be taken into consideration when determining whole-breast radiation delivery techniques?
Recommendation: The choice of whole-breast radiation delivery technique, fractionation, and boost dose should not be dependent on margin width.
Is the presence of lobular carcinoma in situ at the margin an indication for re-excision? Do invasive lobular carcinomas require a wider margin (than no ink on tumor)? What is the significance of pleomorphic lobular carcinoma in situ at the margin?
Recommendation: Wider negative margins than no ink on tumor are not indicated for invasive lobular cancer. Classic lobular carcinoma in situ at the margin is not an indication for re-excision. The significance of pleomorphic lobular carcinoma in situ at the margin is uncertain.
Should increased margin widths be considered for patients of young age (≤ 40 years)?
Recommendation: Young age (≤ 40 years) is associated with both increased ipsilateral breast tumor recurrence after breast-conserving therapy and increased local relapse on the chest wall after mastectomy and is also more frequently associated with adverse biologic and pathologic features. There is no evidence that increased margin width removes the increased risk of ipsilateral breast tumor recurrence in young patients.
What is the significance of an extensive intraductal component in the tumor specimen, and how does this affect margin width?
Recommendation: An extensive intraductal component identifies patients who may have a large residual ductal carcinoma in situ burden after lumpectomy. There is no evidence of an association between increased risk of ipsilateral breast tumor recurrence when margins are negative.
ASCO Qualifying Statements
The ASCO panel stated that it reinforces and amplifies the guideline authors’ call for monitoring of outcomes at the institutional level during the transition to adoption of the SSO/ASTRO recommendations. The panel authors noted, “Margin assessments can be influenced by institution-specific practices related to specimen handling, imaging, and processing. Outcome monitoring should include frequency of re-excision, rates of local recurrence, and the institutional or program standard for defining a minimal negative margin thickness (ie, distance between cancer cells and inked margin surface on microscopic specimen sections) as being adequate.”
The panel noted that use of the guideline will likely result in narrower margins and fewer patients undergoing re-excision. Thus, the panel urges heightened emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications. The authors stated, “If narrower margins become more common as a consequence of the SSO/ASTRO guideline, post-lumpectomy mammography for cases that involve satellite lesions or microcalcifications will be essential to insure adequate resection of the primary site of disease before proceeding to breast
irradiation.”
Finally, the panel noted the inherent weaknesses, particularly selection bias, of the retrospective, observational studies that form the basis of many of the SSO/ASTRO recommendations, and thus urged that flexibility be used in application of the guideline. The panel quotes Jagsi and colleagues, in a recent comment on the guideline in International Journal of Radiation Oncology Biology Physics,3 who commended the SSO/ASTRO guideline authors for avoiding the “blanket prescription of behavior,” and thus allowing clinicians to make more individualized treatment decisions.
In this regard, it is noted that the guideline states that it is not known whether the recommendations apply to women treated with accelerated partial-breast irradiation. Further, as suggested by Jagsi et al, re-excision might be reasonably considered in patients who are underrepresented in the studies included in the SSO/ASTRO analysis, including, for example, a young patient with “multiple very close margins of less than 1 mm across a broad front, an extensive intraductal component, and large breasts that would
easily accommodate a re-excision.”3
The authors concluded, “The ASCO ad hoc guideline review panel has reviewed the SSO/ASTRO guideline and endorses the adoption of the guideline, with minor qualifications.” ■
Disclosure: Dr. Newman reported no potential conflicts of interest.
References
1. Buchholz TA, Somerfield MR, Griggs JJ, et al: Margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology consensus guideline. J Clin Oncol. April 7, 2014 (early release online).
2. Moran MS, Schnitt SJ, Giuliano AE, et al: Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer. Ann Surg Oncol 21:704-716, 2014; Int J Radiat Oncol Biol Phys 88:553-564, 2014; J Clin Oncol. February 10, 2014 (early release online).
3. Jagsi R, Smith BD, Sabel M, et al: Individualized, patient-centered application of consensus guidelines to improve the quality of breast cancer care. Int J Radiat Oncol Biol Phys 88:535-536, 2014.
