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Background: The current standard for the preoperative marking of non-palpable breast lesions is wire guided localization (WGL) which is associated with logistical efforts and patient discomfort. Non-radioactive seeds (NRS) recently challenged the use of WGL; but do they provide a better alternative from a logistical and environmental perspective?, Methods: WGL standard was compared with NRS available in Germany: Magseed®, Pintuition®, SAVI SCOUT ® and LOCalizer™ on a logistical and carbon-footprinting basis. In the logistical analysis the number of patient contacts with the healthcare system for lesion localization/removal and the number of breast punctures were evaluated in two different clinical scenarios (primary surgery and secondary surgery after neoadjuvant treatment). The carbon footprints of WGL and NRS (with exception of LOCalizer) were assessed based on their material compositions and operating energy in a streamlined approach., Results: Application of NRS reduces the number of contacts by 33.3 % (2 vs. 3) in primary, by 50 % (2 vs. 4) in secondary surgery, and the number of breast punctures by 33.3 % (2 vs.3). Annual Germany-wide material- and energy-based carbon footprints of NRS (1.6-3.2 tons CO 2 eq) are significantly lower in comparison to WGL (10.3 tons CO 2 eq). The implementation of NRS would lead to a CO 2 eq reduction by around 79 % compared to WGL., Conclusions: The use of NRS for the localization of non palpable breast lesions is more favorable from the environmental and logistical perspective, when compared to WGL with possible benefits for patients, healthcare providers and the environment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thorsten Kuehn reports a relationship with Merit Medical Systems, Hologic, Sirius Medical Systems, and Endomag that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival., Methods: From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan-Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models., Results: In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77-1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85-1.50, p = 0.414) for OS, 1.21 (95% CI 0.89-1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73-1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients., Conclusions: Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring., (© 2023. The Author(s).)

Background: As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer?, Material and Methods: We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated., Results: Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy "hormonal treatment"., Conclusions: Support of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer., (© 2023. The Author(s).)

Purpose: Although the incidence of distant relapse is decreasing, 20-30% of patients with early breast cancer die of metastasis. The aim of this study is to characterize patients with metastasis-free survival(MFS) less than 5 years, to analyze the most probable site of metastases according to the internally and externally validated BRENDA-score. The BRENDA-score is a combination of the biological subtype and clinical staging., Method: 3832 patients with primary diagnosis of breast cancer and either distant metastatic recurrence within 5 years or MFS ≥ 5 years were assigned to this study. Patients were classified for metastatic recurrence according to the BRENDA-score. 1765 patients were in a validation set. Statistical methods were Kaplan-Meier curves, Cox regression analysis, Exhausted CHAID, likelihood-ratio tests and the Nearest Neighbor Estimation method., Results: There was a significant(p < 0.001) difference between the Kaplan-Meier MFS-functions of M0-patients stratified by BRENDA-score. The BRENDA score outperforms intrinsic subtypes and the Nottingham prognostic score. It fits the original data and the validation set equally well (p = 0.179).There was a significant(p < 0.001) difference between mean BRENDA-Index for patients with MFS < 5y(21.0 ± 9.0) and patients with MFS ≥ 5y(mean BRENDA-Index 11.7 ± 8.2). 55.6% of the very high risk patients(BRENDA-Index ≥ 27) had metastases within 5 years. The most likely primary metastatic site was bone(30%) followed by liver(19%) and lung(18%). The discriminatory ability(areas under the time dependent ROC curve) of the BRENDA score is good to acceptable for the first 5 years. In the very low/low risk (intermediate, high/very high) risk group 50% of all metastases were diagnosed within 26 months. Guideline adherence had a highly significant influence on outcome independent of the risk group., Conclusion: The evaluation showed that the BRENDA-Score is a robust predictive tool for breast cancer recurrence and site of metastases in the first five years after diagnosis. It outperforms intrinsic subtypes and the Nottingham prognostic score. The BRENDA-score could be a tool for a risk orientated and targeted follow up., (© 2023. The Author(s).)

Purpose: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer., Methods: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent., Results: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup., Conclusion: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …).

Introduction: The aim of this survey was to assess the efficacy and the feasibility of scalp cooling (SC) in an outpatient hematological and oncological center in a real-world setting., Methods: We prospectively monitored cancer patients from August 2017 to October 2019 receiving oncological treatments with SC, using the sensor-controlled system "DigniCap." Effectiveness was defined by a self-estimated hair loss < Grad 2 (<50%) according to the Common terminology Criteria for adverse events V4.0 or not requiring a wig. Withdrawal from SC on patient's demand was considered as failure. Tolerability and safety were also evaluated., Results: Ninety-four patients with chemotherapy for their primary (52%) or metastatic (48%) disease had a total of 634 SC sessions. SC was well accepted with increasing experience of the nurses (withdrawal for any reason 29/94). Among the female population (N = 85) 54% received a (neo-)adjuvant chemotherapy. Forty-eight percentages received a taxane-based therapy, 35% anthracycline-based, 17% platin compounds, and others. The overall success rate in the female sample was 72%. In the male group (N = 9), the majority had a metastatic disease (6/9) and received a taxane-based therapy (5/9). The rate of withdrawal by discomfort and pain was high, and the success rate was 44%., Conclusion: Our study confirms the satisfaction of patients with SC to prevent chemotherapy-induced alopecia. SC increases acceptance of the recommendation and administration of chemotherapy and decreases the degree of distress of patients and their treating physicians. Reimbursement remains a major issue in the out patient setting., (© 2022 S. Karger AG, Basel.)

Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. Our retrospective study shows our experience with NGS of 324 genes in combination with protein expression in patients with advanced breast cancer (aBC). The primary purpose was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Between April 2018 and September 2019, 41 patients with aBC were offered a NGS test. The test was used to detect clinically relevant genomic alterations and to support further targeted therapy decisions. Hormone receptors, ERBB2 of tumors and PD-L1 was stained by immunohistochemistry. The data was recorded up to September 2019. After prior consent 41 results were available for further analysis. The most common BC subtypes were triple-negative (n = 16), HR+/ERBB2- (n = 15), and ERBB2+ (n = 9), with one missing data of the primary tumor. 27 patients had more than one genetic alteration. The most common alterations were PIK3CA (n = 14) and ERBB2 alterations (n = 11). Followed by ESR1 (n = 10), FGFR1 (n = 7) and PTEN (n = 7). 68% of the alterations were clinically relevant (tier I and II of ESCAT classification). The most common treatment recommendation was ERBB2-directed therapy (single or double blockade, trastuzumab emtansine and lapatinib) followed by alpelisib in combination with fulvestrant. Comprehensive genomic profiling combined with protein expression analysis in aBC allowed a guided personalized therapy for half of our patients. So far there are no well-defined tools allowing interpretations of genomic alterations detected by NGS in combination with protein expression and other factors.

Introduction: Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected., Methods: The target population includes the German "Alb-Allgäu-Bodensee Region" which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets., Results: Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients., Conclusions: The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.

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.

Background: Despite a trend for less radical surgical approaches in breast cancer due to better understanding of tumour biology and new treatment options such as neoadjuvant chemotherapy (NAC) and intra-operative radiotherapy (IORT), seroma production remains one of the main surgical side effects that can result in prolonged recovery, delay of radiotherapy and patient discomfort. The aim of this study is to provide an update on risk factors for seroma production after breast cancer surgery considering the latest treatment options., Methods: A retrospective analysis of seroma production in primary breast cancer patients treated between 01.01.2010 and 31.12.2014 at the Breast Cancer Centre, University Hospital Ulm, was performed. Patients with previous breast/axillary surgery or more than one intervention were excluded. Seroma formation was measured using wound drains placed in breast and axilla., Results: In total, 581 patients met the inclusion criteria. Median age at diagnosis was 60 years, and median BMI 25.6 kg/m 2 . 60 (10.3%) patients had a mastectomy, 175 (30.1%) patients received IORT, and 72 (12.4%) patients received NAC. Median amount of seroma production was 82.5 ml (range 0-3012.5 ml). Multivariate analysis revealed that most of the observed variation in seroma production was due to type of surgery (mastectomy vs. breast conserving), length of surgery and number of removed lymph nodes. Both NAC and IORT explained a significant but very small amount of the observed variation in seroma production., Conclusion: The most important factors for seroma production are extent and duration of breast surgery.

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 VO 2 , 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.

Purpose: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) for the staging of clinically node-negative breast cancer patients (BCP), demonstrating equivalent survival to ALND while resulting in reduced morbidity. ALND has remained the standard of care for the majority of BCP with clinical axillary metastases or metastases found on SLN biopsy. More recently, it is debated whether ALND could be avoided not only in SLN-negative BCP but also in selected SLN-positive disease or even in all patients. This analysis of pN+ BCP shows the impact of the number of excised lymph nodes on RFS and OAS adjusted by age, tumor size, intrinsic subtypes and adjuvant systemic therapy., Methods: In this retrospective, multicenter cohort study, we investigated data from 2992 pN+ primary BCP recruited from 17 participating certified breast cancer centers in Germany between 2001 and 2008 within the BRENDA study group., Results: The median number of excised lymph nodes was 17. The number of excised lymph nodes was neither significant for RFS (p = 0.085) nor for OAS (p = 0.285). Adjustments were made for age, tumor size and intrinsic subtypes. The most important significant parameters for RFS were intrinsic subtypes (p < 0.001) and tumor size (p < 0.001) and for OAS age (p < 0.001) and intrinsic subtypes (p < 0.001). There were no significant differences in RFS and OAS in any subgroup stratified by the number of excised lymph nodes. Only for T3/T4 tumors, there is a very small significant advantage of ALND for RFS but not for OAS. After adjusting in addition by guideline adherence of adjuvant systemic therapy (AST), intrinsic subtypes and guideline-adherent AST are the most important significant (p < 0.001) parameters for RFS and OAS., Conclusions: The number of excised lymph nodes of pN+ BCP neither correlates with RFS nor with OAS. Survival of pN+ BCP is primarily determined by the biology and the guideline-adherent AST based on the corresponding intrinsic subtypes. These results support the omission of a radical ALND at least for pN+ patients scheduled for breast-conserving surgery (not mastectomy), provided they receive whole breast irradiation and guideline-adherent AST.

Introduction: One of the most common complications in breast conserving surgery is seroma formation. The origin of seroma formation remains unclear. While intraoperative radiotherapy (IORT) has been shown to be an alternative to whole breast irradiation, the influence on seroma production is unclear. Therefore, this analysis compares seroma production in patients with breast conserving surgery with or without IORT as tumour bed boost during breast conserving surgery., Method: A retrospective analysis of seroma production in patients with nodal-negative (pN0sn) pT1/2 primary breast cancer treated between September 2010 and October 2013 at the Breast Cancer Centre, University Hospital Ulm was performed. Patients with neoadjuvant chemotherapy, previous breast/axillary surgery or more than one intervention were excluded. IORT was applied as a tumour bed boost with 50-kV X-rays (Intra beam(®)) delivering 9 Gy at the applicator surface. Seroma formation was measured using wound drains placed in breast and in axilla., Results: Data of 152 patients (99 -IORT; 53 +IORT) were available for analysis. No significant differences between patients with or without IORT with regard to seroma production and number of days until drain removal were found (all p > 0.05)., Conclusion: Patients with IORT encountered no increased seroma production and removal of the drains was not delayed compared to patients with breast conserving surgery only. Our results indicate that IORT does not increase the seroma production compared to surgery alone.

Background: Treatment side effects, comorbidities, and guideline-adherent treatment (GL+) influence the oncologic outcome of older breast cancer patients (oBCP) (age ≥ 70 years). The focus of this analysis was to investigate the associations among tumor characteristics, guideline adherence, and outcome and to compare these associations between younger breast cancer patients (yBCP) (age 50-69 years) and oBCP., Methods: This is a retrospective multicenter cohort study with 17 participating certified breast cancer centers. The analysis of 10,897 patient records collected from 1992 to 2008 for GL+ and clinical outcome was performed. Tumor and patient characteristics and their associations with GL+ were compared between oBCP and yBCP., Results: Nonguideline-adherent treatment (GL-) was associated with higher tumor stages and comorbidities. This effect was stronger in the oBCP group (P < .001). GL+ was significantly more common in yBCP than in oBCP (P < .001). The oBCP had significantly higher tumor stages, including tumor size (P < .001), nodal status (P < .001), and positive hormone receptors (P = .001). Tumor grading was lower (P = .001), and HER2neu overexpression was less frequent (P = .003) in oBCP. Overall survival and disease-free survival are significantly impaired if GL- occurred in patients with breast cancer independently of age., Conclusions: GL- is associated with decreased disease-free survival and overall survival in both age groups. GL+ decreases advanced tumor characteristics in all age groups but significantly more in oBCP. If patients received GL+, we were unable to detect a statistical significant difference in the survival parameters., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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):, 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 HER2neu 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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Extraskeletal osteosarcoma (ESOS) is a rare malignancy, usually arising in older adults. We were unable to find reports of children or adolescents affected by an ESOS of the breast. Here, we present the case of a high-grade osteosarcoma arising in the breast of a 16-year-old girl. The tumor was treated with breast-conserving resections and adjuvant multiagent chemotherapy, based on a regimen of doxorubicin, high-dose methotrexate, cisplatin, and ifosfamide. At last follow-up, the patient was in first complete remission, 29 months after initial diagnosis.

Objective: 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., Methods: 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)., Results: 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)., Conclusion: Despite this finding p21 does not appear to act as an exclusive prognostic marker for breast cancer disease.

The development of breast cancer is a complex process that involves multiple genes at many stages, from initial cell cycle dysregulation to disease progression. To identify genetic variations that influence this process, we conducted a large-scale association study using a collection of German cases and controls and >25,000 SNPs located within 16,000 genes. One of the loci identified was located on chromosome 11q13 [odds ratio (OR)=1.85, P=0.017]. The initial association was subsequently tested in two independent breast cancer collections. In both sample sets, the frequency of the susceptibility allele was increased in the cases (OR=1.6, P=0.01). The susceptibility allele was also associated with an increase in cancer family history (P=0.1). Fine mapping showed that the region of association extends approximately 300 kb and spans several genes, including the gene encoding the nuclear mitotic apparatus protein (NuMA). A nonsynonymous SNP (A794G) in NuMA was identified that showed a stronger association with breast cancer risk than the initial marker SNP (OR=2.8, P=0.005 initial sample; OR=2.1, P=0.002 combined). NuMA is a cell cycle-related protein essential for normal mitosis that is degraded in early apoptosis. NuMA-retinoic acid receptor alpha fusion proteins have been described in acute promyelocytic leukemia. Although the potential functional relevance of the A794G variation requires further biological validation, we conclude that variations in the NuMA gene are likely responsible for the observed increased breast cancer risk.

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.