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Background: The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed?Methods: A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines.Results: 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy.Conclusion: The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate feasibility of an exercise intervention consisting of high-intensity interval endurance and strength training in breast cancer patients. Methods: Twenty-six women with nonmetastatic breast cancer were consecutively assigned to the exercise intervention- (n= 15, mean age 51.9 ± 9.8 years) and the control group (n = 11, mean age 56.9 ± 7.0 years). Cardiopulmonary exercise testing that included lactate sampling, one-repetition maximum tests and a HADS-D questionnaire were used to monitor patients both before and after a supervised six weeks period of either combined high-intensity interval endurance and strength training (intervention group, twice a week) or leisure training (control group). Results: Contrarily to the control group, endurance (mean change of VO2, peak 12.0 ± 13.0%) and strength performance (mean change of cumulative load 25.9 ± 11.2%) and quality of life increased in the intervention group. No training-related adverse events were observed. Conclusions: Our guided exercise intervention could be used effectively for initiation and improvement of performance capacity and quality of life in breast cancer patients in a relatively short time. This might be especially attractive during medical treatment. Long-term effects have to be evaluated in randomized controlled studies also with a longer follow-up. Implications for Rehabilitation: High-intensity interval training allows improvement of aerobic capacity within a comparable short time. Standard leisure training in breast cancer patients is rather suitable for the maintenance of performance capacity and quality of life. Guided high-intensity interval training combined with strength training can be used effectively for the improvement of endurance and strength capacity and also quality of life. After exclusion of contraindications, guided adjuvant high-intensity interval training combined with strength training can be safely used in breast cancer patients [ABSTRACT FROM AUTHOR]

Objective: Planning of breast radiation for patients with breast conserving surgery often relies on clinical markers such as scars. Lately, surgical clips have been used to identify the tumor location. The purpose of this study was to evaluate the geographic miss index (GMI) and the normal tissue index (NTI) for the electron boost in breast cancer treatment plans with and without surgical clips. Material and Methods: A retrospective descriptive study of 110 consecutive post-surgical patients who underwent breast-conserving treatment in early breast cancer, in which the clinical treatment field with the radiologic (clipped) field were compared and GMI/NTI for the electron boost were calculated respectively. Results: The average clinical field was 100 mm (range, 100-120 mm) and the clipped field was 90 mm (range, 80-100 mm). The average GMI was 11.3% (range, 0-44%), and the average NTI was 27.5% (range, 0-54%). The GMI and NTI were reduced through the use of intra-surgically placed clips. Conclusion: The impact of local tumor control on the survival of patients with breast cancer is also influenced by the precision of radiotherapy. Additionally, patients demand an appealing cosmetic result. This makes "clinical" markers such as scars unreliable for radiotherapy planning. A simple way of identifying the tissue at risk is by intra-surgical clipping of the tumor bed. Our results show that the use of surgical clips can reduce the diameter of the radiotherapy field and increase the accuracy of radiotherapy planning. With the placement of surgical clips, more tissue at risk is included in the radiotherapy field. Less normal tissue receives radiotherapy with the use of surgical clips. [ABSTRACT FROM AUTHOR]

Purpose The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y): (1) Is there a significant difference in the distribution of the biological subtypes of oBCP vs younger breast cancer patients (yBCP; 50–69 y)? (2) Which biological subtype has the highest rate of non-guideline-adherent-treatment (GL−) among oBCP? (3) Is a single GL− (i.e. radiotherapy/surgery/endocrine-therapy/chemotherapy) significantly associated with the survival outcome in each biological subgroup? Methods Between 1992 and 2008 the BRENDA (‘BRENDA’ = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714). Results OBCP were more likely to have hormone receptor positive (HR+) and HER2 neu negative (HER2−) breast cancer (77.5% vs 74.5%). The rate of GL− was significantly different (p < 0.001) between the age groups and the biological subgroups (yBCP vs oBCP: 21.8%vs38.8% (HR+/HER2−); 30.6%vs49.7% (HR+/HER2+); 23.6%vs69.5% (HR−/HER2+); 31.4%vs67.8% (TNBC)). The survival parameters for HR+/HER2− and TNBC were significantly worse in case of GL− regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR−/HER2+ tumors for GL− for radiotherapy and in HR+/HER2+ tumors for chemotherapy. Conclusions Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) remains a challenging topic for clinical oncologists. This study sought to evaluate TNBC versus other breast cancer subtypes with respect to survival parameters. We evaluated possible differences in survival in TNBC by age and by the extent to which evidence-based treatment guidelines were adhered.Methods: This German retrospective multi-center cohort study included 9156 patients with primary breast cancer recruited from 1992 to 2008.Results: The rates of guideline adherence are significantly lower in TNBC compared to non-TNBC subtypes. These lower rates of guideline adherence can be observed in all age groups and are most pronounced in the >65 subgroup [<50 (20.9% vs. 42.0%), 50-64 (25.1% vs. 51.1%), and >65 (38.4% vs. 74.6%)]. In TNBC patients of all age groups, disease-free survival and overall survival were associated with an improvement by 100% guideline-adherent adjuvant treatment compared to non-adherence. Furthermore, TNBC patients of all ages had similar outcome parameters if 100% guideline-adherent adjuvant treatment was applied.Conclusion: The rates of guideline-adherent treatment were significantly lower in TNBC, even though guideline adherence was strongly associated with improved survival. In the case of 100% guideline-adherent treatment, no difference in survival was observed over all the age groups examined, even in the group of >65-year-old TNBC patients. [ABSTRACT FROM AUTHOR]

Abrogation of the function of TP53 gene is supposed to lead to a more aggressive breast cancer phenotype that produces a less favorable clinical outcome. The p21 gene on chromosome 6p21.2 can be stimulated by an activated TP53 gene. A product of transcription, the p21 protein, an inhibitor of cyclin-dependent kinases, has its function in gene repair and angiogenesis during cell division, and can regulate apoptosis. The purpose of this analysis was to examine for an association between the genotypes measured on two single nucleotide polymorphisms (SNPs) located within the TP53 and p21 genes. In a clinical epidemiological case–control study, 814 individuals were recruited. 550 samples (275 cases/275 control) of peripheral blood obtained from women (aged 22–87 years) with breast cancer and from healthy women (aged 23–87 years) were genotyped for frequencies of the following gene variances: R72P/rs1042522 ( gene TP53) and S31R/ss4388499 ( gene p21). For the variance in gene TP53 no significant differences between the control group and women with breast cancer could be estimated. For the variance in gene p21 a statistically significant association between the SNP measured within p21 and breast cancer status was observed. The odds ratio for the increased risk for those carrying the CA genotype as opposed to the CC genotype is 1.74 (95% confidence ratio = 1.00–3.05). Despite this finding p21 does not appear to act as an exclusive prognostic marker for breast cancer disease. [ABSTRACT FROM AUTHOR]

Background: Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. Methods and Results: In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3- q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). Highdensity association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases (P = 0.01) and tumor size (P = 0.01). Conclusion: Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity. [ABSTRACT FROM AUTHOR]

Simple Summary: The BRENDA-Score provides an easy to use tool for clinicians to estimate the risk of recurrence in primary breast cancer. The algorithm has been validated via a second independent database and provides five recurrence risk groups. This grouping helps clinicians to encourage high risk patients to undergo the recommended treatment. Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival. [ABSTRACT FROM AUTHOR]