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Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.
Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.
Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.
The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.
Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.
Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).
The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.
Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.
In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.
The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.
"This study offers a clear example of how well-designed observational research can address a relevant clinical question that could not be answered with a randomized controlled trial," said Dr. Ryan P. Merkow and Dr. Clifford Y. Ko.
"Giuliano and colleagues used a highly standardized prospective cohort study, designed to minimize confounding and bias, and yield conclusions that may be as useful as those that might come from [a randomized controlled trial]," they said.
"[Randomized controlled trials] should not be considered the de facto and sole source of high-level evidence." By judiciously using both types of research, "it might be possible to address questions faster, cheaper, and perhaps even better than either approach alone," they noted.
Ryan P. Merkow, M.D., and Clifford Y. Ko, M.D., are with the American College of Surgeons’ division of research and optimal patient care, Chicago. Dr. Merkow is also in the departments of surgery at Northwestern University, Chicago, and at the University of Colorado, Denver. Dr. Ko is also in the department of surgery at the University of California, Los Angeles. Neither Dr. Merkow nor Dr. Ko reported financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Giuliano’s report (JAMA 2011;306:436-7).
"This study offers a clear example of how well-designed observational research can address a relevant clinical question that could not be answered with a randomized controlled trial," said Dr. Ryan P. Merkow and Dr. Clifford Y. Ko.
"Giuliano and colleagues used a highly standardized prospective cohort study, designed to minimize confounding and bias, and yield conclusions that may be as useful as those that might come from [a randomized controlled trial]," they said.
"[Randomized controlled trials] should not be considered the de facto and sole source of high-level evidence." By judiciously using both types of research, "it might be possible to address questions faster, cheaper, and perhaps even better than either approach alone," they noted.
Ryan P. Merkow, M.D., and Clifford Y. Ko, M.D., are with the American College of Surgeons’ division of research and optimal patient care, Chicago. Dr. Merkow is also in the departments of surgery at Northwestern University, Chicago, and at the University of Colorado, Denver. Dr. Ko is also in the department of surgery at the University of California, Los Angeles. Neither Dr. Merkow nor Dr. Ko reported financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Giuliano’s report (JAMA 2011;306:436-7).
"This study offers a clear example of how well-designed observational research can address a relevant clinical question that could not be answered with a randomized controlled trial," said Dr. Ryan P. Merkow and Dr. Clifford Y. Ko.
"Giuliano and colleagues used a highly standardized prospective cohort study, designed to minimize confounding and bias, and yield conclusions that may be as useful as those that might come from [a randomized controlled trial]," they said.
"[Randomized controlled trials] should not be considered the de facto and sole source of high-level evidence." By judiciously using both types of research, "it might be possible to address questions faster, cheaper, and perhaps even better than either approach alone," they noted.
Ryan P. Merkow, M.D., and Clifford Y. Ko, M.D., are with the American College of Surgeons’ division of research and optimal patient care, Chicago. Dr. Merkow is also in the departments of surgery at Northwestern University, Chicago, and at the University of Colorado, Denver. Dr. Ko is also in the department of surgery at the University of California, Los Angeles. Neither Dr. Merkow nor Dr. Ko reported financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Giuliano’s report (JAMA 2011;306:436-7).
Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.
Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.
Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.
The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.
Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.
Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).
The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.
Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.
In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.
The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.
Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.
Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.
Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.
The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.
Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.
Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).
The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.
Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.
In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.
The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.
FROM JAMA
Major Finding: 5-year overall survival was 95.7% and disease-free survival was 92.2% for women who had occult nodal metastases, compared with 95.1% and 90.4%, respectively, for women who had no occult metastases.
Data Source: A 5-year prospective observational cohort study involving 3,904 women with early-stage breast cancer, including 349 whose sentinel nodes were negative for metastases on hematoxylin-eosin testing but positive on immunohistochemical testing.
Disclosures: The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.