Guidelines: No ink on tumor is adequate surgical margin for early-stage breast cancer

Negative surgical margins defined by the absence of any ink on the excised tumor are adequate in most cases of early-stage breast cancer treated with breast-conserving therapy, suggest new consensus guidelines from the Society of Surgical Oncology and American Society for Radiation Oncology.

"The 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 ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," concludes the 12-member multidisciplinary panel. "The routine practice to obtain negative margin widths wider than no ink on tumor is not indicated" (J. Clin. Oncol. 2014 Feb. 10 [doi:10.1200/JCO.2013.53.3935]).

The panel used as their evidence a systematic review and a meta-analysis based on 33 studies having a total of 28,162 patients with stage I or II breast cancer who were treated with breast-conserving surgery plus whole-breast radiation therapy.

Results showed that, compared with peers having negative margins, patients having positive margins were twice as likely to experience an ipsilateral recurrence, regardless of whether they had favorable tumor biology, were given a radiation boost, or received endocrine therapy (Int. J. Radiation Oncol. Biol. Phys. 2014;88:553-64).

But taking wider margins beyond the point of no ink on tumor did not further reduce the risk of ipsilateral recurrence in the patients overall or in a variety of subsets having unfavorable features (young age, aggressive biology, lobular cancers, or tumors with an extensive intraductal component).

"Our hope is that this guideline will ultimately lead to significant reductions in the high re-excision rate for women with early-stage breast cancer undergoing breast-conserving surgery. Based on the consensus panel’s extensive review of the literature, the vast majority of re-excisions are unnecessary because disease control in the breast is excellent for women with early-stage disease when radiation and hormonal therapy and/or chemotherapy are added to a women’s treatment plan," panel cochair Dr. Meena S. Moran of Yale University, New Haven, Conn., commented in a prepared statement.

In an accompanying editorial, Dr. Reshma Jagsi, University of Michigan, Ann Arbor, and her colleagues write, "We agree with the general idea that routine reexcision of close margins (beyond no ink on tumor) is not necessary, and we expect that these guidelines will have a substantial impact on the community of practicing surgeons. Therefore, radiation oncologists should be prepared to encounter an increasing number of patients with microscopically close margins who might have undergone re-excision in previous years" (Int. J. Radiation Oncol. Biol. Phys. 2014;88:535-36).

At the same time, they note that the wording of the new guidelines gives physicians and patients latitude in individualizing decisions about whether re-excision is warranted.

"Physicians applying these guidelines must have an appreciation of the rationale for the recommendations, as well as the limitations of the evidence available, so that they can interpret and apply the guidelines appropriately. Only with a sophisticated understanding of these issues can we, as a profession, continue to deliver individualized care of consistently high quality, avoiding the sort of ‘cookbook medicine’ that serves well neither physicians nor patients," the editorialists conclude.

The studies included in the meta-analysis were published between 1965 and early 2013 and had a median or mean follow-up of at least 4 years. Patients were excluded if they received neoadjuvant chemotherapy or had only ductal carcinoma in situ.

Overall, 78% of the patients studied had negative margins, defined as no ink on the invasive tumor or any ductal carcinoma in situ component. After a median follow-up of 6.6 years, the median prevalence of ipsilateral recurrence was 5.3% overall.

Patients with positive or close margins were twice as likely to have an ipsilateral recurrence (odds ratio, 1.96). In the subset of studies that were able to separate out close margins, risk was elevated with both positive margins (OR, 2.44) and close margins (OR, 1.74).

The adverse impact of positive margins was still evident in analyses taking into account use of a radiation boost (OR, 2.45) and receipt of endocrine therapy (OR, 2.53), and among patients with favorable biology in the form of estrogen receptor–positive tumors (OR, 2.66).

When the impact of the width of the negative margin was evaluated, the risks of ipsilateral recurrence with 2-mm and 5-mm margins were statistically indistinguishable from those with 1-mm margins.

The analysis confirmed that giving systemic therapy (endocrine therapy, chemotherapy, and/or biologic therapy) reduces the risk of ipsilateral recurrence. But the evidence also suggested that in the small number of patients who do not receive this therapy, wider margins beyond no ink on tumor do not further reduce that risk.

In additional findings, there was no evidence that wider margins beyond no ink on tumor are indicated in patients having more aggressive biological subtypes of breast cancer, invasive lobular carcinoma, or tumors with an extensive intraductal component, or in patients aged 40 years or younger.

The panel also concluded that margin width should not dictate the choice of whole-breast radiation therapy delivery technique, fractionation, and boost dose.

Negative surgical margins defined by the absence of any ink on the excised tumor are adequate in most cases of early-stage breast cancer treated with breast-conserving therapy, suggest new consensus guidelines from the Society of Surgical Oncology and American Society for Radiation Oncology.

"The 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 ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," concludes the 12-member multidisciplinary panel. "The routine practice to obtain negative margin widths wider than no ink on tumor is not indicated" (J. Clin. Oncol. 2014 Feb. 10 [doi:10.1200/JCO.2013.53.3935]).

The panel used as their evidence a systematic review and a meta-analysis based on 33 studies having a total of 28,162 patients with stage I or II breast cancer who were treated with breast-conserving surgery plus whole-breast radiation therapy.

Results showed that, compared with peers having negative margins, patients having positive margins were twice as likely to experience an ipsilateral recurrence, regardless of whether they had favorable tumor biology, were given a radiation boost, or received endocrine therapy (Int. J. Radiation Oncol. Biol. Phys. 2014;88:553-64).

But taking wider margins beyond the point of no ink on tumor did not further reduce the risk of ipsilateral recurrence in the patients overall or in a variety of subsets having unfavorable features (young age, aggressive biology, lobular cancers, or tumors with an extensive intraductal component).

"Our hope is that this guideline will ultimately lead to significant reductions in the high re-excision rate for women with early-stage breast cancer undergoing breast-conserving surgery. Based on the consensus panel’s extensive review of the literature, the vast majority of re-excisions are unnecessary because disease control in the breast is excellent for women with early-stage disease when radiation and hormonal therapy and/or chemotherapy are added to a women’s treatment plan," panel cochair Dr. Meena S. Moran of Yale University, New Haven, Conn., commented in a prepared statement.

In an accompanying editorial, Dr. Reshma Jagsi, University of Michigan, Ann Arbor, and her colleagues write, "We agree with the general idea that routine reexcision of close margins (beyond no ink on tumor) is not necessary, and we expect that these guidelines will have a substantial impact on the community of practicing surgeons. Therefore, radiation oncologists should be prepared to encounter an increasing number of patients with microscopically close margins who might have undergone re-excision in previous years" (Int. J. Radiation Oncol. Biol. Phys. 2014;88:535-36).

At the same time, they note that the wording of the new guidelines gives physicians and patients latitude in individualizing decisions about whether re-excision is warranted.

"Physicians applying these guidelines must have an appreciation of the rationale for the recommendations, as well as the limitations of the evidence available, so that they can interpret and apply the guidelines appropriately. Only with a sophisticated understanding of these issues can we, as a profession, continue to deliver individualized care of consistently high quality, avoiding the sort of ‘cookbook medicine’ that serves well neither physicians nor patients," the editorialists conclude.

The studies included in the meta-analysis were published between 1965 and early 2013 and had a median or mean follow-up of at least 4 years. Patients were excluded if they received neoadjuvant chemotherapy or had only ductal carcinoma in situ.

Overall, 78% of the patients studied had negative margins, defined as no ink on the invasive tumor or any ductal carcinoma in situ component. After a median follow-up of 6.6 years, the median prevalence of ipsilateral recurrence was 5.3% overall.

Patients with positive or close margins were twice as likely to have an ipsilateral recurrence (odds ratio, 1.96). In the subset of studies that were able to separate out close margins, risk was elevated with both positive margins (OR, 2.44) and close margins (OR, 1.74).

The adverse impact of positive margins was still evident in analyses taking into account use of a radiation boost (OR, 2.45) and receipt of endocrine therapy (OR, 2.53), and among patients with favorable biology in the form of estrogen receptor–positive tumors (OR, 2.66).

When the impact of the width of the negative margin was evaluated, the risks of ipsilateral recurrence with 2-mm and 5-mm margins were statistically indistinguishable from those with 1-mm margins.

The analysis confirmed that giving systemic therapy (endocrine therapy, chemotherapy, and/or biologic therapy) reduces the risk of ipsilateral recurrence. But the evidence also suggested that in the small number of patients who do not receive this therapy, wider margins beyond no ink on tumor do not further reduce that risk.

In additional findings, there was no evidence that wider margins beyond no ink on tumor are indicated in patients having more aggressive biological subtypes of breast cancer, invasive lobular carcinoma, or tumors with an extensive intraductal component, or in patients aged 40 years or younger.

The panel also concluded that margin width should not dictate the choice of whole-breast radiation therapy delivery technique, fractionation, and boost dose.

Negative surgical margins defined by the absence of any ink on the excised tumor are adequate in most cases of early-stage breast cancer treated with breast-conserving therapy, suggest new consensus guidelines from the Society of Surgical Oncology and American Society for Radiation Oncology.

"The 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 ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," concludes the 12-member multidisciplinary panel. "The routine practice to obtain negative margin widths wider than no ink on tumor is not indicated" (J. Clin. Oncol. 2014 Feb. 10 [doi:10.1200/JCO.2013.53.3935]).

The panel used as their evidence a systematic review and a meta-analysis based on 33 studies having a total of 28,162 patients with stage I or II breast cancer who were treated with breast-conserving surgery plus whole-breast radiation therapy.

Results showed that, compared with peers having negative margins, patients having positive margins were twice as likely to experience an ipsilateral recurrence, regardless of whether they had favorable tumor biology, were given a radiation boost, or received endocrine therapy (Int. J. Radiation Oncol. Biol. Phys. 2014;88:553-64).

But taking wider margins beyond the point of no ink on tumor did not further reduce the risk of ipsilateral recurrence in the patients overall or in a variety of subsets having unfavorable features (young age, aggressive biology, lobular cancers, or tumors with an extensive intraductal component).

"Our hope is that this guideline will ultimately lead to significant reductions in the high re-excision rate for women with early-stage breast cancer undergoing breast-conserving surgery. Based on the consensus panel’s extensive review of the literature, the vast majority of re-excisions are unnecessary because disease control in the breast is excellent for women with early-stage disease when radiation and hormonal therapy and/or chemotherapy are added to a women’s treatment plan," panel cochair Dr. Meena S. Moran of Yale University, New Haven, Conn., commented in a prepared statement.

In an accompanying editorial, Dr. Reshma Jagsi, University of Michigan, Ann Arbor, and her colleagues write, "We agree with the general idea that routine reexcision of close margins (beyond no ink on tumor) is not necessary, and we expect that these guidelines will have a substantial impact on the community of practicing surgeons. Therefore, radiation oncologists should be prepared to encounter an increasing number of patients with microscopically close margins who might have undergone re-excision in previous years" (Int. J. Radiation Oncol. Biol. Phys. 2014;88:535-36).

At the same time, they note that the wording of the new guidelines gives physicians and patients latitude in individualizing decisions about whether re-excision is warranted.

"Physicians applying these guidelines must have an appreciation of the rationale for the recommendations, as well as the limitations of the evidence available, so that they can interpret and apply the guidelines appropriately. Only with a sophisticated understanding of these issues can we, as a profession, continue to deliver individualized care of consistently high quality, avoiding the sort of ‘cookbook medicine’ that serves well neither physicians nor patients," the editorialists conclude.

The studies included in the meta-analysis were published between 1965 and early 2013 and had a median or mean follow-up of at least 4 years. Patients were excluded if they received neoadjuvant chemotherapy or had only ductal carcinoma in situ.

Overall, 78% of the patients studied had negative margins, defined as no ink on the invasive tumor or any ductal carcinoma in situ component. After a median follow-up of 6.6 years, the median prevalence of ipsilateral recurrence was 5.3% overall.

Patients with positive or close margins were twice as likely to have an ipsilateral recurrence (odds ratio, 1.96). In the subset of studies that were able to separate out close margins, risk was elevated with both positive margins (OR, 2.44) and close margins (OR, 1.74).

The adverse impact of positive margins was still evident in analyses taking into account use of a radiation boost (OR, 2.45) and receipt of endocrine therapy (OR, 2.53), and among patients with favorable biology in the form of estrogen receptor–positive tumors (OR, 2.66).

When the impact of the width of the negative margin was evaluated, the risks of ipsilateral recurrence with 2-mm and 5-mm margins were statistically indistinguishable from those with 1-mm margins.

The analysis confirmed that giving systemic therapy (endocrine therapy, chemotherapy, and/or biologic therapy) reduces the risk of ipsilateral recurrence. But the evidence also suggested that in the small number of patients who do not receive this therapy, wider margins beyond no ink on tumor do not further reduce that risk.

In additional findings, there was no evidence that wider margins beyond no ink on tumor are indicated in patients having more aggressive biological subtypes of breast cancer, invasive lobular carcinoma, or tumors with an extensive intraductal component, or in patients aged 40 years or younger.

The panel also concluded that margin width should not dictate the choice of whole-breast radiation therapy delivery technique, fractionation, and boost dose.