Smaller margins too close for comfort in breast cancer

NATIONAL HARBOR, MD. – Small surgical margins can mean big trouble for patients with breast cancer, said investigators at the annual Society of Surgical Oncology Cancer Symposium.

A retrospective study of outcomes for 2,377 women who underwent either breast-conserving therapy or mastectomy revealed that margins less than 2 mm resulted in a substantial risk of residual disease for all patients, reported Dr. Erin Garvey, a general surgery resident at Mayo Clinic Arizona in Phoenix.

"A policy of re-excision for margins less than 2 mm, coupled with a standardized multidisciplinary approach to breast cancer surgery, results in excellent re-excision and 5-year local recurrence rates. The local recurrence rate is higher, however, for those patients who complete breast-conserving therapy, thus warranting appropriate patient counseling regarding re-excision options and long-term outcome expectations," she said.

In a separate study, investigators from the University of Texas M.D. Anderson Cancer Center, Houston, reported 10-year follow-up data for women who opted for mastectomy to treat ductal carcinoma in situ (DCIS). They found that the incidence of local-regional recurrence (LRR) increased as the surgical margins shrank, and that close margins were the only independent predictor of LRR, reported Dr. Elizabeth FitzSullivan, a surgery fellow at M.D. Anderson.

"However, the local-regional recurrence rate in these patients is so low that routine postmastectomy radiation therapy is not warranted," she said.

No accord on margins

Despite multiple studies and meta-analyses, there is no standard for acceptable margin width in breast cancer, and surveys of both surgeons and radiation oncologists have shown wide variations in preferred margin widths, Dr. Garvey said.

Her group hypothesized that patients with invasive ductal carcinoma without an extensive in situ component who had surgical margins of at least 1 mm would have no evidence of residual disease on re-excision.

To test the idea, they took a retrospective look at records from a prospective database on 2,377 patients who underwent a total of 2,520 procedures from January 2000 through May 2012.

Of this group, 1,498 (63%) underwent lumpectomy, and 180 (12%) required re-excision surgery: 10% who had breast-conserving surgery alone, and 2% whose surgeries were converted to mastectomies. Of the 158 patients who had completed breast-conserving therapy following re-excision, 50 (32%) had residual disease, as did 20 of the 27 patients whose procedures were converted to mastectomies.

Of the 37% (879) who had up-front mastectomies, 2% (19) had re-excision, and of this group, 5 patients had residual disease.

In all, 40% of patients with positive margins had residual disease, compared with 38% of those with margins from 0.1 to 0.9 mm, and 33% for those with margins from 1.0 to 1.9 mm.

In univariate analysis, the presence of residual disease on re-excision did not show any significant association with age, race, menopausal status, width of the closest final margin, hormone receptor status, tumor histology, triple-negative disease, or the presence of angiolymphatic invasion. There was a trend, albeit nonsignificant, toward an association between residual disease and more than one margin narrower than 2 mm, Dr. Garvey noted.

At a median follow-up of 43 months (range, 0-140 months), 5-year local recurrence rates were 1.9% for patients who had breast-conserving therapy, and 1.1% for those who had mastectomy.

Patients who underwent breast-conserving therapy without re-excision had a 5-year local recurrence rate of 1.8%, compared with 4.3% for those who required re-excision, and 0% for those whose procedures were converted to mastectomy.

There was a nonsignificant trend toward higher local recurrence rates for breast-conserving therapy in patients who had re-excisions, which became significant when those patients who had conversion to mastectomy were excluded, with a hazard ratio compared with no re-excision of 2.56 (P = .04).

Narrower margins, larger risk

Dr. FitzSullivan and her M.D. Anderson colleagues reviewed the records of 810 women treated with mastectomy for DCIS from 1996 to 2009. They looked at the final width of histologic margins, defining disease-free margins as those of 3 mm or greater.

In all, 4 patients had positive margins, 59 had margins of 1 mm or smaller, and 35 had margins from 1.1 to 2.9 mm.

In multivariate analysis, independent predictors of close or positive margins were pathologic tumor size of 1.5 cm or greater (odds ratio, 5.11; P = .001), multicentric disease (OR, 5.44; P = .026), and the presence of necrosis (OR, 2.5; P = .003). Neither age, postmenopausal status, skin-sparing mastectomy, nor immediate breast reconstruction were significantly associated with close or positive margins, however.

None of seven patients who underwent postmastectomy radiotherapy had local-regional recurrences. Of the 803 patients who did not receive postsurgery radiation, 10-year LRR rates were 1%, consisting of 7 cases of invasive disease and 1 of DICS. Five patients had surgical management, and the remaining 3 had no further treatment.

When the researchers stratified the local recurrence rates by margin status, they saw that 5% of patients with margins of 1 mm or smaller had LRRs within 10 years, as did 3.6% of those with margins from 1.1 to 2.9 mm, compared with just 0.07% of those with disease-free margins (P less than .001). There was no difference in LRR between the two narrow-margin groups.

Among 546 patients with an intact contralateral breast, the 10-year rate of contralateral breast disease was 6.4%.

On univariate analysis, significant predictors of LRR included margin status (P = .002), multicentric disease (P = .005), and necrosis (P = .005). On multivariate analysis, however, only margin status remained significant, with an HR of 8.0 (P = .006).

Dr. FitzSullivan said that the low rate of LRR of DCIS treated with mastectomy and close surgical margins, compared with the rate of contralateral breast cancer, suggests that routine postmastectomy radiation therapy is not warranted, and should be reserved only for those patients with close or positive surgical margins that cannot be surgically excised.

Each study was internally funded. Dr. Garvey and Dr. FitzSullivan reported having no financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Small surgical margins can mean big trouble for patients with breast cancer, said investigators at the annual Society of Surgical Oncology Cancer Symposium.

A retrospective study of outcomes for 2,377 women who underwent either breast-conserving therapy or mastectomy revealed that margins less than 2 mm resulted in a substantial risk of residual disease for all patients, reported Dr. Erin Garvey, a general surgery resident at Mayo Clinic Arizona in Phoenix.

"A policy of re-excision for margins less than 2 mm, coupled with a standardized multidisciplinary approach to breast cancer surgery, results in excellent re-excision and 5-year local recurrence rates. The local recurrence rate is higher, however, for those patients who complete breast-conserving therapy, thus warranting appropriate patient counseling regarding re-excision options and long-term outcome expectations," she said.

In a separate study, investigators from the University of Texas M.D. Anderson Cancer Center, Houston, reported 10-year follow-up data for women who opted for mastectomy to treat ductal carcinoma in situ (DCIS). They found that the incidence of local-regional recurrence (LRR) increased as the surgical margins shrank, and that close margins were the only independent predictor of LRR, reported Dr. Elizabeth FitzSullivan, a surgery fellow at M.D. Anderson.

"However, the local-regional recurrence rate in these patients is so low that routine postmastectomy radiation therapy is not warranted," she said.

No accord on margins

Despite multiple studies and meta-analyses, there is no standard for acceptable margin width in breast cancer, and surveys of both surgeons and radiation oncologists have shown wide variations in preferred margin widths, Dr. Garvey said.

Her group hypothesized that patients with invasive ductal carcinoma without an extensive in situ component who had surgical margins of at least 1 mm would have no evidence of residual disease on re-excision.

To test the idea, they took a retrospective look at records from a prospective database on 2,377 patients who underwent a total of 2,520 procedures from January 2000 through May 2012.

Of this group, 1,498 (63%) underwent lumpectomy, and 180 (12%) required re-excision surgery: 10% who had breast-conserving surgery alone, and 2% whose surgeries were converted to mastectomies. Of the 158 patients who had completed breast-conserving therapy following re-excision, 50 (32%) had residual disease, as did 20 of the 27 patients whose procedures were converted to mastectomies.

Of the 37% (879) who had up-front mastectomies, 2% (19) had re-excision, and of this group, 5 patients had residual disease.

In all, 40% of patients with positive margins had residual disease, compared with 38% of those with margins from 0.1 to 0.9 mm, and 33% for those with margins from 1.0 to 1.9 mm.

In univariate analysis, the presence of residual disease on re-excision did not show any significant association with age, race, menopausal status, width of the closest final margin, hormone receptor status, tumor histology, triple-negative disease, or the presence of angiolymphatic invasion. There was a trend, albeit nonsignificant, toward an association between residual disease and more than one margin narrower than 2 mm, Dr. Garvey noted.

At a median follow-up of 43 months (range, 0-140 months), 5-year local recurrence rates were 1.9% for patients who had breast-conserving therapy, and 1.1% for those who had mastectomy.

Patients who underwent breast-conserving therapy without re-excision had a 5-year local recurrence rate of 1.8%, compared with 4.3% for those who required re-excision, and 0% for those whose procedures were converted to mastectomy.

There was a nonsignificant trend toward higher local recurrence rates for breast-conserving therapy in patients who had re-excisions, which became significant when those patients who had conversion to mastectomy were excluded, with a hazard ratio compared with no re-excision of 2.56 (P = .04).

Narrower margins, larger risk

Dr. FitzSullivan and her M.D. Anderson colleagues reviewed the records of 810 women treated with mastectomy for DCIS from 1996 to 2009. They looked at the final width of histologic margins, defining disease-free margins as those of 3 mm or greater.

In all, 4 patients had positive margins, 59 had margins of 1 mm or smaller, and 35 had margins from 1.1 to 2.9 mm.

In multivariate analysis, independent predictors of close or positive margins were pathologic tumor size of 1.5 cm or greater (odds ratio, 5.11; P = .001), multicentric disease (OR, 5.44; P = .026), and the presence of necrosis (OR, 2.5; P = .003). Neither age, postmenopausal status, skin-sparing mastectomy, nor immediate breast reconstruction were significantly associated with close or positive margins, however.

None of seven patients who underwent postmastectomy radiotherapy had local-regional recurrences. Of the 803 patients who did not receive postsurgery radiation, 10-year LRR rates were 1%, consisting of 7 cases of invasive disease and 1 of DICS. Five patients had surgical management, and the remaining 3 had no further treatment.

When the researchers stratified the local recurrence rates by margin status, they saw that 5% of patients with margins of 1 mm or smaller had LRRs within 10 years, as did 3.6% of those with margins from 1.1 to 2.9 mm, compared with just 0.07% of those with disease-free margins (P less than .001). There was no difference in LRR between the two narrow-margin groups.

Among 546 patients with an intact contralateral breast, the 10-year rate of contralateral breast disease was 6.4%.

On univariate analysis, significant predictors of LRR included margin status (P = .002), multicentric disease (P = .005), and necrosis (P = .005). On multivariate analysis, however, only margin status remained significant, with an HR of 8.0 (P = .006).

Dr. FitzSullivan said that the low rate of LRR of DCIS treated with mastectomy and close surgical margins, compared with the rate of contralateral breast cancer, suggests that routine postmastectomy radiation therapy is not warranted, and should be reserved only for those patients with close or positive surgical margins that cannot be surgically excised.

Each study was internally funded. Dr. Garvey and Dr. FitzSullivan reported having no financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Small surgical margins can mean big trouble for patients with breast cancer, said investigators at the annual Society of Surgical Oncology Cancer Symposium.

A retrospective study of outcomes for 2,377 women who underwent either breast-conserving therapy or mastectomy revealed that margins less than 2 mm resulted in a substantial risk of residual disease for all patients, reported Dr. Erin Garvey, a general surgery resident at Mayo Clinic Arizona in Phoenix.

"A policy of re-excision for margins less than 2 mm, coupled with a standardized multidisciplinary approach to breast cancer surgery, results in excellent re-excision and 5-year local recurrence rates. The local recurrence rate is higher, however, for those patients who complete breast-conserving therapy, thus warranting appropriate patient counseling regarding re-excision options and long-term outcome expectations," she said.

In a separate study, investigators from the University of Texas M.D. Anderson Cancer Center, Houston, reported 10-year follow-up data for women who opted for mastectomy to treat ductal carcinoma in situ (DCIS). They found that the incidence of local-regional recurrence (LRR) increased as the surgical margins shrank, and that close margins were the only independent predictor of LRR, reported Dr. Elizabeth FitzSullivan, a surgery fellow at M.D. Anderson.

"However, the local-regional recurrence rate in these patients is so low that routine postmastectomy radiation therapy is not warranted," she said.

No accord on margins

Despite multiple studies and meta-analyses, there is no standard for acceptable margin width in breast cancer, and surveys of both surgeons and radiation oncologists have shown wide variations in preferred margin widths, Dr. Garvey said.

Her group hypothesized that patients with invasive ductal carcinoma without an extensive in situ component who had surgical margins of at least 1 mm would have no evidence of residual disease on re-excision.

To test the idea, they took a retrospective look at records from a prospective database on 2,377 patients who underwent a total of 2,520 procedures from January 2000 through May 2012.

Of this group, 1,498 (63%) underwent lumpectomy, and 180 (12%) required re-excision surgery: 10% who had breast-conserving surgery alone, and 2% whose surgeries were converted to mastectomies. Of the 158 patients who had completed breast-conserving therapy following re-excision, 50 (32%) had residual disease, as did 20 of the 27 patients whose procedures were converted to mastectomies.

Of the 37% (879) who had up-front mastectomies, 2% (19) had re-excision, and of this group, 5 patients had residual disease.

In all, 40% of patients with positive margins had residual disease, compared with 38% of those with margins from 0.1 to 0.9 mm, and 33% for those with margins from 1.0 to 1.9 mm.

In univariate analysis, the presence of residual disease on re-excision did not show any significant association with age, race, menopausal status, width of the closest final margin, hormone receptor status, tumor histology, triple-negative disease, or the presence of angiolymphatic invasion. There was a trend, albeit nonsignificant, toward an association between residual disease and more than one margin narrower than 2 mm, Dr. Garvey noted.

At a median follow-up of 43 months (range, 0-140 months), 5-year local recurrence rates were 1.9% for patients who had breast-conserving therapy, and 1.1% for those who had mastectomy.

Patients who underwent breast-conserving therapy without re-excision had a 5-year local recurrence rate of 1.8%, compared with 4.3% for those who required re-excision, and 0% for those whose procedures were converted to mastectomy.

There was a nonsignificant trend toward higher local recurrence rates for breast-conserving therapy in patients who had re-excisions, which became significant when those patients who had conversion to mastectomy were excluded, with a hazard ratio compared with no re-excision of 2.56 (P = .04).

Narrower margins, larger risk

Dr. FitzSullivan and her M.D. Anderson colleagues reviewed the records of 810 women treated with mastectomy for DCIS from 1996 to 2009. They looked at the final width of histologic margins, defining disease-free margins as those of 3 mm or greater.

In all, 4 patients had positive margins, 59 had margins of 1 mm or smaller, and 35 had margins from 1.1 to 2.9 mm.

In multivariate analysis, independent predictors of close or positive margins were pathologic tumor size of 1.5 cm or greater (odds ratio, 5.11; P = .001), multicentric disease (OR, 5.44; P = .026), and the presence of necrosis (OR, 2.5; P = .003). Neither age, postmenopausal status, skin-sparing mastectomy, nor immediate breast reconstruction were significantly associated with close or positive margins, however.

None of seven patients who underwent postmastectomy radiotherapy had local-regional recurrences. Of the 803 patients who did not receive postsurgery radiation, 10-year LRR rates were 1%, consisting of 7 cases of invasive disease and 1 of DICS. Five patients had surgical management, and the remaining 3 had no further treatment.

When the researchers stratified the local recurrence rates by margin status, they saw that 5% of patients with margins of 1 mm or smaller had LRRs within 10 years, as did 3.6% of those with margins from 1.1 to 2.9 mm, compared with just 0.07% of those with disease-free margins (P less than .001). There was no difference in LRR between the two narrow-margin groups.

Among 546 patients with an intact contralateral breast, the 10-year rate of contralateral breast disease was 6.4%.

On univariate analysis, significant predictors of LRR included margin status (P = .002), multicentric disease (P = .005), and necrosis (P = .005). On multivariate analysis, however, only margin status remained significant, with an HR of 8.0 (P = .006).

Dr. FitzSullivan said that the low rate of LRR of DCIS treated with mastectomy and close surgical margins, compared with the rate of contralateral breast cancer, suggests that routine postmastectomy radiation therapy is not warranted, and should be reserved only for those patients with close or positive surgical margins that cannot be surgically excised.

Each study was internally funded. Dr. Garvey and Dr. FitzSullivan reported having no financial disclosures.

[email protected]