Metastatic Work-Up Not Needed for All N2/N3 Breast Cancers

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.

HOT SPRINGS, VA. – An analysis of a prospectively collected database indicates that breast cancer patients with multiple nodal disease need a metastatic work-up only if they have tumor grade 3 or 4.

Current NCCN (National Comprehensive Cancer Network) guidelines recommend that patients with stage III and node-positive disease receive a work-up if they are N1. But the NCCN guidelines are less clear about what to do about N2 and N3 patients, said Dr. Quyen Chu at the annual meeting of the Southern Surgical Association.

About 20% of patients with stage III disease will have distant metastases, said Dr. Chu, chief of the surgical oncology division at Louisiana State University Health Sciences Center, Shreveport.

He and his colleagues at LSU extracted data from an ongoing, prospective breast cancer database, which was created in 1998 and comprises patient experience primarily from the LSU center but also from E.A. Conway Hospital in Monroe, La. They analyzed 256 patients with N2 or N3 disease who began treatment in 2010.

There was little difference between the two groups. The mean age of the 158 N2 patients was 58 years; it was 57 for the 68 N3 patients. The mean tumor grade was 2.5, and the mean tumor size was 4.6 cm. The tumor stage was similar between the two groups, with about 40% overall staged at T2.

"Are we risking an observation based on the play of chance?"

About half of the tumors were estrogen receptor positive overall. There was no difference in estrogen receptor status between the two groups. But more of the N3 patients had HER2-positive tumors, at 43% (31 of 72 patients), compared with 26% (27 of 103 patients) for the N2 group.

The primary end point for the study was the incidence of stage IV disease, either at the time of diagnosis or within 30 days of surgery. Patients underwent bone scans, CT, and/or PET to detect metastases.

Unexpectedly, the researchers found two T0 patients and 35 T1 patients who had stage III metastatic disease. The overall risk of stage IV disease was 16%. In all, 6% of T2 patients had stage IV disease, compared with 22% of T3 patients and 36% of T3 patients.

By N stage, about 83% of N2 and N3 patients had stage III disease, whereas 15% of each group had stage IV disease.

There was no difference in overall survival between the N2 and N3 groups, but those with stage IV disease had a predictably and statistically significant lower overall survival. Using a Cox proportional hazard model, the researchers determined that the only significant predictors of survival were T stage and grade.

Commenting on the paper, Dr. William C. Wood said that Dr. Chu’s observations were "unique," and that the data might help clinicians to more accurately judge tumor progression. "The rate of progression is very important to prognosis," said Dr. Wood, professor of surgery at Emory University in Atlanta. He cautioned, however, that the data set was small. Given that there was no difference in prognosis among the N2 and N3 groups, he asked, "Are we risking an observation based on the play of chance?"

Dr. Wood also suggested that there might not be any utility to identifying patients who had asymptomatic stage IV disease. Staging studies could be avoided, along with potential false positives, and the decision to not identify such patients "could avoid a longer period [of] awareness of stage IV disease in a person who could otherwise be blissfully unaware," he said.

Dr. Chu agreed that this was a valid question. But he suggested that newer agents and aggressive surgical intervention have been shown recently to potentially extend survival in stage IV disease.

Several other commentators wondered if the findings had prompted any change at LSU. "This paper by no means suggests we should change our standard of care," said Dr. Chu. It might prompt some review of the role of different imaging modalities used, he noted. And he added that the study should cause clinicians to question the biology of breast cancer.

"A lot of us have the preconceived notion that if you have N2 or N3 disease, [the] outcome is very bad. But in actuality, it may not be the case," he said. "You may have a subset [of patients] who do quite well, who are true stage III rather than stage IV."

Dr. Chu reported no conflicts.