breast cancer ( bc ) is the most common cancer among american women , with more than 200,000 new cases diagnosed each year . the lifetime risk for developing breast cancer has been reported to be as high as 12% , whereas the risk of death has been reported to be as high as 5% . in mexico in 2007 , there were 16,340 reported hospitalizations for breast cancer and 4,872 breast cancer - related deaths . the introduction of mammography screening protocols in recent decades has facilitated the detection of breast cancer at increasingly earlier stages . for example , in the usa , stage 0 or i disease was found in 56% of cases in 1995 in comparison to only 45% in 1985 . today , we are able to detect bc at earlier stages ; however , according to the literature , cases of locoregional and distant recurrences have been reported in 5 to 40% of cases . this wide range of reported results is probably due to inadequate axillary dissection , incomplete surgical technique , or suboptimal systemic treatment . the involvement of the axillary lymph nodes ( lns ) is the most important prognostic factor for recurrence in the early stages of bc according to the literature . patients with cancer - positive ln have been reported to have a four to eight times higher mortality rate in comparison to patients with negative lymph nodes . there is also a direct correlation of positive ln status with the risk of distant recurrence . in patients with negative ln , patients with tumors that were smaller than 1  cm in diameter had an overall 5-year survival rate of 99% , whereas patients with tumors of 35  cm in diameter had a survival rate of 86% . the scarff - bloom richardson ( sbr ) grading system takes into account the mitotic index and the differentiation and pleomorphism of the tumor . according to these characteristics , tumors can be well- , medium- , and poorly - differentiated ( grades 1 , 2 , or 3 , resp . ) . grade 3 tumors have a relative recurrence risk of 4.4 times higher compared to the reference group . this prognostic factor has a significant relevance in patients with small tumors and negative lns .   in clinical stage i , some studies have reported a recurrence risk of 38% when lymphovascular invasion ( lvi ) is present in comparison to 22% in cases where lvi is absent ; however , some studies have not found any differences . histologically , tubular , mucinous , tubulolobular , and cribriform breast tumors have the best prognoses . ductal , lobular solid , and mixed - type ( ductal and lobular ) tumors have a 10-year os in only 50% of cases . the worst prognosis occurs with inflammatory carcinoma , which has a 10-year os in 30% of cases . hormone receptor status ( hr ) is both a prognostic and predictive factor in bc . a recent study has found that patients with positive hr had a higher percentage of 5-year dfs and os . other authors have found that hr are a prognostic factor , and hr are a strong predictive factor in relation to adjuvant treatment with tamoxifen or aromatase inhibitors [ 14 , 15 ] . c - erb b-2 ( her2/neu ) is present in 2030% of bc patients . her2/neu is detected in tumors that are hr negative , have lymphatic infiltration , have high mitotic indices , and are bcl-2 negative . patients with positive lns and the presence or absence of her2/neu expression have a 10-year os in 50% and 65% of the cases , respectively . her2/neu expression can be used as a predictive factor of patient response to alkylating chemotherapy . tumors with her2 neu expression responded well and had a better survival rate in comparison to her2 neu negative tumors , when treated with anthracycline - based chemotherapy . the expression of her2/neu is a predictor of patient response to trastuzumab ( herceptin ) , wherein 4% of patients have a complete response , 17% a partial response , and 30% stable disease . the grade of tumor proliferation can be measured in several different ways , and these different methodologies have been evaluated as prognostic factors . some of these different methodologies include ki-67 , the mitotic index , and the s - phase fraction [ 2022 ] . genetic profiling ( microarray ) is typically used to identify gene expression profiles , which could help in the identification of prognostic or predictive factors in patients with small tumors and negative ln . studies have reported increased bc - related death rates among obese patients , in addition to a twofold increased risk of a contralateral breast cancer . the intent of this study was to analyze the prognostic and predictive factors that are responsible for locoregional or distant recurrences in a group of patients treated at the national cancer institute of mexico . this retrospective transversal study included all of the patients who presented with a recurrence of a treated breast cancer from january 1 to december 31 , 2007 , at the national cancer institute of mexico ( incan ) . a total of 11,144 patients were treated from january 1 , 1986 , to december 31 , 2006 , and a total of 60 of these patients showed a recurrence in 2007 . the control group consisted of 60 other patients who were matched by clinical stage , time , type of treatment , and age . all of the information used in this study was obtained from the clinical archive of the incan . the revised data used in this investigation consisted of pathology reports of true cut biopsies or the definitive operative material . in the majority of cases , disease recurrence was diagnosed using imaging techniques ( ct of the lung and abdomen using a siemens somatom volumen zoom 2003 ; nuclear bone scanning using a siemens gama camera series signature e.cam ; abdominal ultrasound using a siemens antares acuson premium ; or x - ray of the chest wall using a philips super 80  cp diagnost 15 ) . both groups received adequate surgical interventions and neoadjuvant or adjuvant therapy during their primary treatments according to the guidelines of the nccn . vascular invasion was defined as tumor penetration into the lumen of an artery or vein . vascular invasion should only be diagnosed when the tumor is demonstrated within one or both of a pair of vessels . extracapsular extension ( ece ) was determined by a rupture of the axillary node membrane or when tumor cells were found in perinodular tissue . if the lymph node capsule was infiltrated but not penetrated , this was considered as ece - absent . immunohistochemical staining for the her2 protein was performed using the dako herceptest immunocyto - chemical assay ( dako , glostrup , denmark ) on 4-m - thick sections of formalin - fixed , paraffin - embedded material by the pathology unit of our institute and according to the manufacturer 's instructions . this staining was scored as follows : 0 or 1 + , no staining or membrane staining in < 10% of tumor cells or barely perceptible and incomplete membrane staining in > 10% of the tumor cells ; 2 + , weak to moderate complete membrane staining in > 10% of tumor cells ; 3 + , intense and complete membrane staining in > 10% of tumor cells . if ihc staining was indeterminate ( 2 + ) , then the fish method was conducted as a follow - up test . recurrence was defined as an occurrence of disease six or more months after the last treatment . statistical analyses were performed using the statistical package for the social sciences software ( version 15.0 ; spss , chicago , il , usa ) . the chi - squared or fisher 's exact test was used to compare categorical variables . univariate and multivariate logistic regression were used to identify recurrence - associated factors . for categorical variables with multiple levels , the reference level was set to that with the lowest probability of the dependent variable . variables with a p < 0.2 in the univariate analysis were entered into the model using a forward stepwise procedure . the results were summarized as odds - ratios ( or ) and respective 95% confidence intervals ( ci ) . the area under the receiver operating characteristic curve ( aurocc ) was used to evaluate the ability of the model to discriminate between patients in the recurrence and control groups . a goodness - of - fit ( hosmer - lemeshow ) in this series , the median age of the patients was 44.75 years ( range 2573 ) in the recurrence group ( rg ) and 44.3 years ( range 2574 ) in the control group ( cg ) . the median tumor size was 5.08  cm ( range 112  cm ) in the rg and 4.35  cm ( range 110  cm ) in the cg . the median number of ln in the dissected material consisted of 16  ln in both groups ( with a range from 235 in the rg and 238 in the cg ) . some of the patients from both groups , depending on their clinical stage , were treated with chemotherapy , radiotherapy , and chemoradio therapy as a neoadjuvant treatment . in 42 patients ( 70% ) of the rg , we used different regimens of neoadjuvant chemotherapy , depending on the patient and tumor characteristics . the aforementioned treatment regimens have been applied in recent years for the breast cancer . after treatment with neoadjuvant chemotherapy , the clinical responses of patients to these treatments were analyzed . therein , 52% of patients in the rg , who presented with stable or progressive disease and were clinically or mammographically diagnosed following the neoadjuvant chemotherapy , were treated with chemoradio concomitant treatment or with radiotherapy alone . all of the patients were treated with surgery , and the type of surgery used in each case is presented in table 2 . the number of positive lns and the tumor response therein in the group of patients who had been treated with neoadjuvant treatment were analyzed , and the results are summarized in table 3 . all of the patients who had positive hr were treated with adjuvant hormone therapy for five years . approximately 20  mg tamoxifen was given to 43% of these patients ( table 4 ) . the median time of recurrence in our patients was 46.1 months ( 95% ci 34.857.4 ) , as illustrated in figure 1 . in the rg the results of the univariate analyses to identify the independent risk factors of early recurrence in the breast cancer are presents in table 6 .   on table 7 , the multivariate analyses were used to identify the independent risk factors of early recurrence in the breast cancer . in this study , patients younger than 35 years of age ( 15% of the analyzed group ) did not present with the usual tumor characteristics that have been previously reported such as big tumor size , positive ln , negative hr , and her2/neu expression ) . this subgroup exhibited a tumor size , negative hr , positive axillary ln , and her2/neu expression that were similar to those of the recurrence group ( 5.8  cm and 5.08  cm , 55.6% and 45.2% , 62.5% and 73.3% , and 25% and 23.8% , resp . ) . the clinical stage and skin involvement of patients in the analyzed group were used as criteria for comparisons to the cg , which is the reason why we did not include these attributes as prognostic factors . nevertheless , 55% of group had locoregional advanced clinical stage tumor , whereas 42% had skin involvement at the time of diagnosis .   in a study involving 70 patients with locally advanced clinical stage disease presentation ( iii - c ) and who were treated with a combined modality treatment , a disease - free survival ( dfs ) and a median overall survival ( os ) of 1.9 years and 3.5 years , respectively , statistical analyses demonstrated a longer dfs ( 2.8 years ) in group of locally advanced clinical stage disease presentation ( iiia , iiib , iiic ) . this observation can be explained because of the aggressive locoregional treatment , which is standard treatment in our department for this group of patients . the group with advanced clinical stage disease presentation ( iib , iiia , iiib , and iiic ) were not statistically at higher risk for earlier recurrence in comparison to group with earlier stages of disease presentation ( p = 0.084 ic 0.7119.14 ) , and this observation has been confirmed by a multivariate analysis . this result is not similar to a report from montagna , who observed a 57% recurrence - free survival rate in the first two years of remission . in this series , it was not possible to confirm the findings of galea et al . , who observed that tumor histology predicted the recurrence rate or influenced the 10-year survival rate . it has been reported in the literature that tumor histological grade could be a relevant recurrence prediction factor , especially in small tumors with negative ln . in this study , we did not confirm the predictive value of histological grading , probably because the 85% of patients in rg and cg had large tumors with positive ln . after performing a univariate analysis on the results , lvi was confirmed as a prognostic factor for tumor recurrence in this study , which agrees with the 60% higher mortality rate in patients when lvi is present , reported in the literature ; however , subsequent multivariate analyses exclude the role of lvi as prognostic factor for tumor recurrence . hr was observed not to be predictive of breast recurrence and disease - free interval when the two groups were compared after four years . this observation disagrees with the results reported by the nsabp b-06 study , which found that patients with positive hr had a higher percentage of 5-year dfs and os , compared to patients with negative hr . this has been explained by the presumption that the predictive power of hr is only relevant in the first three years , because these tumors are usually well differentiated and their growth is slower . when the positive hr was compared to the negative hormone receptors in the recurrence group , we found that 69% of patients with positive hr ( estrogen , progesterone , or both ) did not present with an early recurrence ( up to 24 months from the termination of the initial therapy ) ( 30.9 versus 69.1%  p = 0.014 ) . patients with negative hr did not show a statistically significant difference in terms of early or late recurrence .   in this series , the histopathological reports could not distinguish gross from focal extracapsular extension ( ece ) , which is most likely why ece was not identified as a prognostic factor . positive ln was identified as the most important prognostic factor for recurrence in this study . this observation agrees with those obtained by the nsabp study , which reported 5-year overall survival rates of 83% , 73% , 46% , and 28% for negative ln , 13 positive lns , 412 positive lns , and more than 13 positive lns , respectively . there were no differences in the expression of her2/neu in the recurrence and control groups , and we could not confirm her2/neu as a prognostic factor for recurrence in this study . these results are different from the findings reported in the literature [ 30 , 31 ] . we believe that these results are because of the small number of patients with her2/neu expression in both groups analyzed . patients in the recurrence group exhibited a significantly lower complete pathological response in comparison to patients in the control group . we confirmed that patients with a complete pathological response had a lower risk of recurrence . in this study , the extent of nodal involvement and the complete pathological response to neoadjuvant chemotherapy were the most important predictors of breast cancer recurrence .