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SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS