the cohort for this study consisted of 603 patients who underwent breast resection at sun yat - sen university cancer center for breast cancer between january 3 , 1990 and january 6 , 2005 .
the age at diagnosis ranged from 19 to 82 years ( median , 56 years ) .
all patients had axillary lymph node dissections without evidence of lymph node metastasis and all primary tumors were confined to the breast (  5.0 cm ) .
tumor size and lymph node number were obtained from the original macroscopic and microscopic descriptions of specimens .
eighty - eight percent of the patients underwent modified radical mastectomies , and the remaining 12% underwent partial breast resections .
a total of 27 surgeons performed the operations , and 18 pathologists were involved in pathologic diagnosis .
the patients were stratified into two groups based on the number of tumor - free lymph nodes removed : group a , 10 or fewer lymph nodes , and group b , more than 10 lymph nodes .
follow - up information obtained from sun yat - sen university cancer center for each patient began at the date of surgery and ended with either the date of death or the study termination date ( february 1 , 2014 ) .
patients were followed for 1283 months , with a median follow - up time of 126 months .
death information was directly collected by the cancer center through active physician follow - up or direct communications with next of kin .
demographic data by the number of lymph nodes removed were analyzed by chi - square test .
cox proportional hazards regression was used to examine the independent association between the number of tumor - free lymph nodes removed and the risk of death from breast cancer .
models included age ( < 40 , 4150 , 5160 , 6170 , and 71 or more years ) , marital status ( not married , married , or unknown ) , tumor size , grade , and adjuvant therapy .
tumor size was recoded as 1 cm or less ( ajcc stage t1a and b ) , 1.1 to 2.0 cm ( stage t1c ) , and 2.1 to 5.0 cm ( stage t2 ) .
tumor grade was classified as 1 ( well differentiated ) , 2 ( moderately differentiated ) , 3 ( poorly differentiated ) , or 4 ( anaplastic or undifferentiated ) .
the cohort for this study consisted of 603 patients who underwent breast resection at sun yat - sen university cancer center for breast cancer between january 3 , 1990 and january 6 , 2005 .
the age at diagnosis ranged from 19 to 82 years ( median , 56 years ) .
all patients had axillary lymph node dissections without evidence of lymph node metastasis and all primary tumors were confined to the breast (  5.0 cm ) .
tumor size and lymph node number were obtained from the original macroscopic and microscopic descriptions of specimens .
eighty - eight percent of the patients underwent modified radical mastectomies , and the remaining 12% underwent partial breast resections .
a total of 27 surgeons performed the operations , and 18 pathologists were involved in pathologic diagnosis .
the patients were stratified into two groups based on the number of tumor - free lymph nodes removed : group a , 10 or fewer lymph nodes , and group b , more than 10 lymph nodes .
follow - up information obtained from sun yat - sen university cancer center for each patient began at the date of surgery and ended with either the date of death or the study termination date ( february 1 , 2014 ) .
patients were followed for 1283 months , with a median follow - up time of 126 months .
death information was directly collected by the cancer center through active physician follow - up or direct communications with next of kin .
demographic data by the number of lymph nodes removed were analyzed by chi - square test .
cox proportional hazards regression was used to examine the independent association between the number of tumor - free lymph nodes removed and the risk of death from breast cancer .
models included age ( < 40 , 4150 , 5160 , 6170 , and 71 or more years ) , marital status ( not married , married , or unknown ) , tumor size , grade , and adjuvant therapy .
tumor size was recoded as 1 cm or less ( ajcc stage t1a and b ) , 1.1 to 2.0 cm ( stage t1c ) , and 2.1 to 5.0 cm ( stage t2 ) .
tumor grade was classified as 1 ( well differentiated ) , 2 ( moderately differentiated ) , 3 ( poorly differentiated ) , or 4 ( anaplastic or undifferentiated ) .
in all cases , the proportion of patients with 10 or fewer tumor - free lymph nodes removed was 60.7% , and the proportion with more than 10 tumor - free lymph nodes removed was 39.3% .
the 5- and 10-year survival rates were higher for patients in group a , who had 10 or fewer tumor - free lymph nodes removed , than for patients in group b , who had more than 10 tumor - free lymph nodes removed ( 88.0% and 66.4% vs. 69.2% and 51.5% , respectively , p < 0.001 ; figure 1 ) . in the multivariate cox proportional hazards models with all patients , the adjusted hazard ratios ( hrs ) for risk of death from breast cancer were higher for patients with larger tumors ( p < 0.001 ) , patients with tumors of higher grade ( p < 0.01 ) , and patients who did not undergo adjuvant therapy ( p < 0.001 ) .
it was also elevated for patients who were younger at diagnosis but was lower for married patients versus unmarried patients ( table 2 ) . compared with patients with primary tumor 1 cm or less in diameter , patients with primary tumor 1.1 to 2.0 cm in diameter and patients with primary tumor 2.1 to 5.0 cm in diameter
had higher adjusted hrs for risk of death from breast carcinoma of 1.539 [ 95% confidence interval ( ci ) , 1.2681.901 ; p < 0.001 ] and 2.351 ( 95% ci , 1.7962.889 ; p
the adjusted hrs for risk of death from breast cancer were elevated for high or unknown tumor grade versus low tumor grade ( adjusted hr = 1.288 and p = 0.006 for grades 3 and 4 ; adjusted hr = 1.795 and p < 0.001 for unknown grade ) . compared with patients who did not undergo adjuvant therapy , patients undergoing adjuvant therapy had a lower adjusted hr for risk of death from breast cancer ( adjusted hr , 0.352 ; 95% ci , 0.2960.433 ; p < 0.001 ) .
the adjusted hr for patients with 10 or fewer nodes removed was significantly reduced compared with that for patients with more than 10 nodes removed ( adjusted hr , 0.579 ; 95% ci , 0.4920.687 ; p < 0.001 ) .
kaplan - meier analysis indicated differences in survival curves between group a and group b ( p < 0.001 ) .
in this study , we found that patients who had more than 10 tumor - free lymph nodes removed had a higher risk of death from breast cancer compared with patients who had 10 or fewer tumor - free lymph nodes removed .
we chose 10 as a critical value because the median number of lymph nodes removed in this study was 10 , which was similar to the value in a previous study . hence , simple pursuit of a higher number of tumor - free lymph nodes removed may be of little use for improving survival rate .
our finding of an association between the number of tumor - free lymph nodes removed and the risk of death from causes other than breast cancer suggests possible confounding with comorbidity . in other words , surgeons may not want to perform axillary dissection , or may perform less extensive dissection , on patients with comorbid conditions .
in contrast to previous reports , this study also included analysis of adjuvant therapy , which was useful for lymph node  negative patients , as a possible confounding factor ; a previous report suggested adjuvant therapy had prognostic significance in patients with lymph node  negative breast cancer .
thus , although camp et al . reported results similar to ours , they did not take into account of adjuvant therapy as a possible confounding factor .
our results were also in contrast to those from other studies. sosa et al . studied 464 patients with lymph node  negative invasive breast cancer that was 2 cm or smaller in diameter and found better survival among those with 10 or more ( up to 33 ) lymph nodes removed compared with those with fewer than 10 lymph nodes removed .
however , their analysis did not include tumors larger than 2 cm in diameter , and the number of deaths was too small for separate analysis of mortality from breast cancer versus other causes .
similarly , studies by moorman et al . and polednak are limited by misclassifications ( as indicated by reabstracting and recoding audits of stage and disease extent ) , the number of lymph nodes removed , and tumor size .
other factors associated with the risk of death from breast cancer including age at diagnosis , marital status , tumor size , tumor grade , and adjuvant treatment were consistent with those reported in the literature,,. the observation that women with more tumor - free lymph nodes removed had a higher risk of death from metastatic breast cancer may be explained by the lack of host immune responses or defense by lymph nodes . under this hypothesis ,
other studies have focused on the prognostic benefit of host immune responses to tumor  in particular , peritumoral lymphocytic infiltrates and alterations in the architecture of tumor - draining lymph nodes such as sinus histiocytosis. recent studies have begun to define the cytokines underlying lymph node genesis and hyperplasia. hyperplasia after lymph node genesis can occur as a downstream reaction to inflammation and/or tumor . in another study , 25% of the breast carcinomas examined expressed mrna for vascular endothelial growth factor - c ( vegf - c ) , which specifically induces lymphangiogenesis , .
however , further exploration is needed for the role of lymphangiogenic and lymph node development factors , especially in the context of tumor size and grade , as these factors may play a role in tumor metastasis for lymph node - negative breast cancer .
a large proportion of patients underwent resection for breast cancer before 1998 , when advances in adjuvant therapy were slim in china .
notably , whether adjuvant therapy should be used after dissection in patients with lymph node - negative breast cancer remains to be determined .
even if removal of more nodes did not , in itself , improve survival , which is a controversial issue , adjuvant therapy may be withheld from some node - negative patients , including a subgroup misclassified as node - negative .
weir et al . demonstrated the recovery of a small number of negative lymph nodes at axillary dissection likely understages patients and leads to undertreatment , resulting in an increased regional relapse rate and poorer survival .
the implication of a small number of nodes removed is that it reduces the prognostic value of the negative nodal status .
for a variety of reasons , positive nodes have likely been missed in some of these patients , resulting in more regional relapses and poorer survival .
thus , increases would occur in both the proportion of lymph node - positive cases with extensive nodal involvement ( easily detected clinically or by removal of only a few nodes ) and the proportion of false - negatives among lymph node - negative cases .
the 5-year and 10-year survival rates of lymph node - negative patients would ostensibly decrease over time , but overall survival of all breast cancer patients would not decline unless either removal of nodes had a direct therapeutic effect or changes occurred in the use of adjuvant therapies that improve survival .
another trend may be toward the use of a combination of pathologic and biologic tumor characteristics as predictors of axillary node status , at least for small tumors and especially for cases in which adjuvant therapy decisions do not rest fully on confirmation of nodal status.
 recently , there has been controversy about the relationship between the number of lymph nodes removed and survival of patients diagnosed with lymph node - negative breast cancer . to assess this relationship , 
 603 cases of lymph node - negative breast cancer with a median of 126 months of follow - up data were studied . 
 patients were stratified into two groups ( group a , 10 or fewer tumor - free lymph nodes removed ; group b , more than 10 tumor - free lymph nodes removed ) . 
 the number of tumor - free lymph nodes in ipsilateral axillary resections as well as 5 other disease parameters were analyzed for prognostic value . 
 our results revealed that the risk of death from breast cancer was significantly associated with patient age , marital status , histologic grade , tumor size , and adjuvant therapy . 
 the 5- and 10-year survival rates for patients with 10 or fewer tumor - free lymph nodes removed was 88.0% and 66.4% , respectively , compared with 69.2% and 51.1% , respectively , for patients with more than 10 tumor - free lymph nodes removed . for patients with 10 or fewer tumor - free lymph nodes removed , 
 the adjusted hazard ratio ( hr ) for risk of death from breast cancer was 0.579 ( 95% confidence interval , 0.492 - 0.687 , p < 0.001 ) , independent of patient age , marital status , histologic grade , tumor size , and adjuvant therapy . 
 our study suggests that the number of tumor - free lymph nodes removed is an independent predictor in cases of lymph node - negative breast cancer . 
Patients and Methods
Study population
Follow-up
Statistical analysis
Results
Discussion