Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes: Risk Pattern and Outcomes on a Community Level.

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0-3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR*/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR*/HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR*/HER2- breast cancer with 0-3 positive lymph nodes and RS <25.

Extensive monitoring of the natural menstrual cycle using the serum biomarkers estradiol, luteinizing hormone and progesterone.

Expected values for estradiol (E2), luteinizing hormone (LH), and progesterone determined in serum allow accurate assessment of menstrual cycle phase. Automated immunoassays demonstrate variable degrees of bias, emphasizing the need to establish method-specific reference values. We therefore established method-specific reference intervals for the Elecsys® LH assay and new generation Elecsys Estradiol III and Progesterone III assays (cobas e 801 analyzer) in 85 apparently healthy women aged 22-37 (US)/18-37 (EU) years over one natural menstrual cycle. Cycle length and day of ovulation were standardized; phases were defined by LH surge and/or progesterone/E2 levels. Median (5th-95th percentile) concentrations (follicular/ovulation/luteal) were E2: 198 â€‹pmol/L (114-332), 757 â€‹pmol/L (222-1959) and 412 â€‹pmol/L (222-854); LH: 7.14 IU/L (4.78-13.2), 22.6 IU/L (8.11-72.7) and 6.24 IU/L (2.73-13.1); progesterone: 0.212 â€‹nmol/L (0.159-0.616), 1.81 â€‹nmol/L (0.175-13.2) and 28.8 â€‹nmol/L (13.1-46.3). Sub-phase (early/intermediate/late) reference values were also determined for follicular and luteal phases. This multicenter study established reliable, method-specific E2, LH and progesterone reference values that could assist clinical decision-making in women with fertility disorders and monitoring of natural cycles in assisted reproductive treatment.

Effect of Dry Needling on Thigh Muscle Strength and Hip Flexion in Elite Soccer Players.

PURPOSE: Increase in muscle force, endurance, and flexibility is desired in elite athletes to improve performance and to avoid injuries, but it is often hindered by the occurrence of myofascial trigger points. Dry needling (DN) has been shown effective in eliminating myofascial trigger points. METHODS: This randomized controlled study in 30 elite youth soccer players of a professional soccer Bundesliga Club investigated the effects of four weekly sessions of DN plus water pressure massage on thigh muscle force and range of motion of hip flexion. A group receiving placebo laser plus water pressure massage and a group with no intervention served as controls. Data were collected at baseline (M1), treatment end (M2), and 4 wk follow-up (M3). Furthermore, a 5-month muscle injury follow-up was performed. RESULTS: DN showed significant improvement of muscular endurance of knee extensors at M2 (P = 0.039) and M3 (P = 0.008) compared with M1 (M1:294.6 ± 15.4 N·m·s, M2:311 ± 25 N·m·s; M3:316.0 ± 28.6 N·m·s) and knee flexors at M2 compared with M1 (M1:163.5 ± 10.9 N·m·s, M2:188.5 ± 16.3 N·m·s) as well as hip flexion (M1: 81.5° ± 3.3°, M2:89.8° ± 2.8°; M3:91.8° ± 3.8°). Compared with placebo (3.8° ± 3.8°) and control (1.4° ± 2.9°), DN (10.3° ± 3.5°) showed a significant (P = 0.01 and P = 0.0002) effect at M3 compared with M1 on hip flexion; compared with nontreatment control (-10 ± 11.9 N·m), DN (5.2 ± 10.2 N·m) also significantly (P = 0.049) improved maximum force of knee extensors at M3 compared with M1. During the rest of the season, muscle injuries were less frequent in the DN group compared with the control group. CONCLUSION: DN showed a significant effect on muscular endurance and hip flexion range of motion that persisted 4 wk posttreatment. Compared with placebo, it showed a significant effect on hip flexion that persisted 4 wk posttreatment, and compared with nonintervention control, it showed a significant effect on maximum force of knee extensors 4 wk posttreatment in elite soccer players.

Gustatory and olfactory function in breast cancer patients.

PURPOSE: Loss of appetite is a common complaint in cancer patients. There is still no overall conclusion whether this symptom might be caused by distorted taste/smell function or by tumor byproducts. This knowledge would be important for adequate patient counseling as well as symptom relief. Several studies investigated taste function, but to our knowledge, only one studied olfactory function in cancer patients. MATERIALS AND METHODS: Sixty-nine breast cancer patients were investigated by a validated taste (taste strips) and smell test (Sniffin' Sticks) prior to chemotherapy. RESULTS: Compared to normative data, breast cancer patients showed no significant difference in odor threshold, but better scores for odor identification and odor discrimination. For taste, breast cancer patients showed a significantly lower value for the quality sour compared to healthy controls only on left side of the tongue; there was no difference in the qualities sweet, salty, and bitter. An increase in tumor size was associated with a significant decrease in olfactory function, but not in gustatory function. Different histology or graduation of breast cancer, resection status, or metastasis to the lung and liver had no influence on taste and smell. There was no correlation between taste and smell to estrogen or progesterone receptor status. There was no correlation between smell and human epidermal growth factor receptor 2 (Her2 status), but there was a significant correlation between bitter taste and Her2 status. CONCLUSION: Taste/smell did not seem substantially altered in breast cancer patients compared to normative data. Nevertheless, increasing tumor burden resulted in decreased olfactory function, but not in taste changes.

Family history of pilonidal sinus predisposes to earlier onset of disease and a 50% long-term recurrence rate.

PURPOSE: It has long been suspected that a family history of pilonidal sinus disease may predispose to higher disease incidence. The influence of family history on recurrence rate has not been investigated. The purpose of this study was to evaluate the recurrence rate in patients with both a personal and a family history of pilonidal sinus disease. METHODS: A standardized telephone interview was used to retrospectively study 578 patients who underwent primary surgery between 1980 and 1996. Differences concerning the long-term recurrence rate between patients with a positive or negative family history were analyzed using Kaplan-Meier statistics. RESULTS: Sixty-eight of 578 patients (12%) had a positive family history with first-degree relatives, in which 28 brothers and 25 fathers were similarly involved. The long-term recurrence rate was significantly elevated when family history was positive (35% vs. 22% after 15 years and 52% vs. 28% after 25 years; P = 0.02). The long-term recurrence rate was elevated if surgery was needed at a younger age (P = 0.03). The body mass index measured at time of admission for surgery did not seem to have any negative influence on recurrence rates (P = 0.31). Although a positive family history predisposes a person to earlier onset of disease, recurrences occur within 5.1 +/- 6.2 years (mean +/- standard deviation) in patients with a positive family history and within 5.3 +/- 5.2 years in patients with a negative family history (P = 0.95). CONCLUSION: Patients with a positive family history need closer surgical monitoring because primary disease will manifest earlier. A remarkable long-term recurrence rate exceeding 50% after 25 years places a much higher disease burden on patients with a positive family history. All available interventions known to reduce recurrence rate should be applied to this group of patients.

Circulating vascular endothelial growth factors and their soluble receptors in pre-invasive, invasive and recurrent cervical cancer.

AIM: To study the impact of circulating vascular endothelial growth factors (VEGF) -A, -C and -D and their soluble receptors VEGFR-1/-2 on disease invasion and progression in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. PATIENTS AND METHODS: Blood samples were obtained from 125 women, including 50 cases of CIN, 51 of PCC and 24 of RCC, before treatment. Soluble (s) biomarker levels were determined by ELISA and tested for correlation with histopathological factors. RESULTS: With disease progression, sVEGF-A (p = 0.007) and sVEGFR-2 (p = 0.014) significantly increased, while sVEGF-D (p = 0.046) decreased. sVEGFR-2 levels were increased in node+ patients (p = 0.024) and in metastatic disease (p = 0.003). sVEGF-A values were higher in HPV+ cases (p = 0.019). In detecting disease invasiveness, sensitivity and specificity were 76% and 48% for sVEGF-A, 52% and 32% for sVEGF-D, 25% and 94% for sVEGF-C, 93% and 6% for sVEGFR-1 and 73% and 34% for sVEGFR-2, respectively. CONCLUSION: In cervical neoplasia, a switch from a lymphangiogenic phenotype towards a hemangiogenic phenotype occurs with disease invasion and progression. The sensitivity and specificity values, however, seem not convincing enough to establish these factors as clinical markers for disease invasiveness in cervical cancer.

Qualitative and quantitative assessment of taste and smell changes in patients undergoing chemotherapy for breast cancer or gynecologic malignancies.

PURPOSE: Smell and taste changes during chemotherapy are significant complaints of cancer patients. Loss of olfactory/gustatory function can lead to malnutrition, weight loss, and possibly a prolonged morbidity of chemotherapy-induced adverse effects, decreased quality of life, poor compliance, and even decreased therapy response. This prospective study comprehensively investigated, to our knowledge for the first time, smell and taste changes in a cohort of 87 patients undergoing chemotherapy for breast cancer or gynecologic malignancies. PATIENTS AND METHODS: Olfactory function was tested using Sniffin' Sticks (Burghart; Wedel, Germany) and gustatory function was tested using taste strips before, during, and immediately and 3 months after chemotherapy. RESULTS: Olfactory and gustatory function significantly decreased during chemotherapy and recovered almost completely 3 months after chemotherapy. Scores of odor thresholds were affected more than those of discrimination or identification. The olfactory function of older patients was affected more than that of younger patients. There was no difference in the olfactory function during chemotherapy with respect to the chemotherapeutic agent or initial diagnosis (breast or ovarian cancer). Regarding taste, scores of salty taste were affected more than scores of sweet, sour, or bitter taste. The gustatory function did not differ significantly during chemotherapy with respect to age or diagnosis but did differ with respect to the chemotherapeutic agent. Taxane-based chemotherapy caused the most severe disorders. CONCLUSION: Chemotherapy has a significant but transient effect on olfactory and gustatory function, possibly causing reduced appetite, a low energy intake, and weight loss. Additional spices and flavoring may compensate for this diminished chemosensory function, enhancing patient compliance and quality of life.

Graft preconditioning with low-dose tacrolimus (FK506) and nitric oxide inhibitor aminoguanidine (AGH) reduces ischemia/reperfusion injury after liver transplantation in the rat.

Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (LTx). Recent evidence indicates that an increase in nitric oxide (NO) production after LTx is associated with I/R injury. The aim of this study was to demonstrate that low-dose FK506 in combination with aminoguanidine (AGH), which leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx. Fortyone DA-(RT1av1) rats served as donors and recipients for syngenic orthotopic arterialised LTx. They were divided into 4 groups: controls without pre-/treatment (I), pre-/treatment with high-dose FK506 (II), pre-/treatment with AGH only (III), and pre-/treatment with low-dose FK506 in combination with AGH (IV). After LTx the laboratory parameters and liver biopsy were performed. The levels of transaminase (ALT) in groups I, II and III were significantly higher on day 3 after LTx compared to group IV (p = 0.001, p = 0.001, p = 0.000). In group IV the I/R-associated liver necrosis rate was reduced significantly. Our results demonstrated that a combined dual pharmacological pretreatment (group IV) reduced I/R injury of the graft after LTx in a rat model.

Cerebral gunshot wounds: a score based on three clinical parameters to predict the risk of early mortality.

BACKGROUND: To provide a score to predict the risk of early mortality after single craniocerebral gunshot wound (GSW) based on three clinical parameters. METHODS: All patients admitted to Baragwanath Hospital, Johannesburg, South Africa, between October 2000 and May 2005 for an isolated single craniocerebral GSW were retrospectively evaluated for the documentation of (i) blood pressure (BP) on admission; (ii) inspection of the bullet entry and exit site; and (iii) initial consciousness (n= 214). RESULTS: Conscious GSW victims had an early mortality risk of 8.3%, unconscious patients a more than fourfold higher risk (39.2%). Patients with a systolic BP between 100 and 199 mm Hg had an 18.2% risk of mortality. Hypotension (<100 mm Hg) doubled this risk (37.7%) and severe hypertension (> or =200 mm Hg) was associated with an even higher mortality rate of 57.1%. Patients without brain spilling out of the wound ('non-oozer') exhibited a mortality of 19.7%, whereas it was twice as high (43.3%) in patients with brain spill ('oozer'). By logistic regression, a prognostic index for each variant of the evaluated parameters could be established: non-oozer:0, oozer:1, conscious:0, unconscious:2, 100 < or =RR(sys) < 200 mm Hg:0, RR(sys) < 100 mm Hg:1, RR(sys)>/= 200 mm Hg:2. This resulted in a score (0-5) by which the individual risk of early mortality after GSW can be anticipated. CONCLUSIONS: Three immediately obtainable clinical parameters were evaluated and a score for predicting the risk of early mortality after a single craniocerebral GSW was established.

Procalcitonin ratio indicates successful surgical treatment of abdominal sepsis.

BACKGROUND: On-demand relaparotomy has been associated with a slightly decreased mortality compared to planned relaparotomy in the surgical treatment of secondary peritonitis. On-demand relaparotomy must be performed without delay to detect progressing sepsis early, before the onset of multiorgan failure. The aim of the study was to evaluate procalcitonin (PCT) as a parameter for early detection of progressing sepsis after operative treatment of the infective source. METHODS: In 104 consecutive patients with secondary peritonitis, PCT serum levels were monitored on postoperative days 1 and 2 after initial operative elimination of the septic focus. The PCT ratio between postoperative days 1 and 2 was calculated and correlated to the success of the initial intervention. The latter was considered inadequate if relaparotomies were necessary to eliminate the intraabdominal infection. RESULTS: Using classification and regression tree analysis, a cutoff could be calculated at 1.03 for the PCT ratio of postoperative day 1 to day 2. Lesser values indicated unsuccessful elimination of the septic source, whereas values above 1.03 represented successful operative treatment of the septic focus. Unsuccessful treatment of the septic process could be detected with a specificity of 63% and a sensitivity of 95%. CONCLUSION: The PCT ratio appears to be a valuable aid in deciding if further relaparotomies are necessary after initial operative treatment of an intraabdominal septic focus.

Reduced lymph node yield in rectal carcinoma specimen after neoadjuvant radiochemotherapy has no prognostic relevance.

BACKGROUND: In colorectal surgery UICC/AJCC criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. Neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined. METHODS: One hundred two patients with uT3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with uT3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. Total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival. RESULTS: After neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p < 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p = 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. Reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. Overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39% for 0, 1-3, and more than 3 positive lymph nodes (p < 0.0001). CONCLUSION: The UICC/AJCC criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients.

Patellar height before and after unicompartmental knee arthroplasty: association with early clinical outcome?

INTRODUCTION: There is paucity of information available concerning the role of patellar height in unicompartmental knee arthroplasty (UKA). The present study was conducted to determine the patellar height before and after UKA and to assess possible effects on the early clinical outcome. MATERIALS AND METHODS: We measured the patellar height before and after UKA in 83 consecutive knees using the Blackburne-Peel (BP) index and Insall-Salvati (IS) ratio and investigated the impact of the patellar height on the clinical outcome 2 years after surgery. RESULTS: BP values significantly decreased from 0.81 before surgery to 0.76 postoperatively (P < 0.001). IS ratios did not significantly decrease from 1.02 to 1.01 (P = 0.108). Lower preoperative BP values were negatively correlated with the postoperative knee extension (r = -0.357, P = 0.026), while higher preoperative BP values were negatively associated with the postoperative Knee Society Score (r = -0.302, P = 0.046). Lower preoperative IS values were negatively correlated with postoperative Knee Scores (r = -0.394, P = 0.019). CONCLUSION: After UKA, the patellar height decreased significantly according to the BP index, but not significantly according to the IS ratio. We found only weak and inconsistent correlations between the patellar height and clinical outcome parameters. Hence, based on the present results, the patellar height seems not to be a strict separate patient-selection criterion for UKA.

Association of body mass index and clinical outcome 2 years after unicompartmental knee arthroplasty.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has gained in popularity during the last years. However, the body mass index (BMI) of patients undergoing UKA is controversially discussed in the literature. There is, moreover, a paucity of information available concerning the association of BMI with early clinical outcomes after UKA. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 83 consecutive UKA, 2 years after surgery, and investigated the potential association of BMI and the outcome variables Knee Society Score (KSS), University of California at Los Angeles (UCLA) activity levels, anterior knee pain (AKP), range of motion, and implant failure. RESULTS: The KSS and UCLA significantly increased from 132 and 4.7 preoperatively to 187.5 and 7.1, respectively, after surgery. Knee flexion significantly improved from 123.7 to 128.4 degrees and the prevalence of extension deficiencies significantly decreased from 28.9 to 15.7%. Three knees (3.6%) failed and were converted to total knee arthroplasty. Failures were not associated with increased BMI (P = 0.387). The BMI had no significant association with KSS values, UCLA levels, and implant failure. We found a weak negative correlation between BMI and postoperative knee flexion (r = -0.285, P = 0.009) and a moderate positive correlation between BMI and the intensity of AKP (r = 0.525, P < 0.001). CONCLUSION: The results of the present study suggest that the BMI of patients undergoing UKA has no major impact on the early clinical outcome 2 years after surgery. There was, however, a definite correlation between the BMI and AKP. Longer follow-up is necessary to determine if overweight and obesity may increase revision rates after UKA.

The influence of retrograde reperfusion on the ischaemia-/reperfusion injury after liver transplantation in the rat.

Dysfunction of the graft after liver transplantation caused by ischaemia-/reperfusion (I/R) injury is a serious clinical problem. The aim of this study was to evaluate the influence of different kinds of reperfusion on I/R injury in a rat model. Arterialized orthoptic rat liver treatment was performed on male LEWIS-(RT(1))-rats. Three groups (n = 7) were formed. Group I: antegrade reperfusion with a 6-min delayed reperfusion via the hepatic artery. Group II: Antegrade reperfusion, simultaneously, via the portal vein and the hepatic artery. Group III: Retrograde reperfusion via the vena cava. Serum parameters were determined one, 24 and 48 h after operation. Furthermore, after 48 h, the liver was taken for histological assessment. After 48 h, rats of group III showed significantly lower aspartate amino transferase and alanine amino transferase serum levels compared with group I and group II rats. Forty-eight hours after transplantation, glutamate dehydrogenase serum level was significantly lower in group III than in group II. In histology, group III livers showed significantly less necrotic spots than group I and group II livers. Maximum size of the necrotic spots was significantly lower in group III than in group I. Also, significantly more necrotic spots were seen in the 'Rappaport's zone' 1 and 2 of group I than in group III. Our data suggested that the expression of I/R-injury correlates with the type of reperfusion. Furthermore, under standard conditions, this study was able to demonstrate that in a rat model, the retrograde reperfusion leads to a lower expression of I/R-injury than the antegrade reperfusion.

Use of procalcitonin for early prediction of lethal outcome of postoperative sepsis.

BACKGROUND: To develop strategies for the prediction of sepsis outcome systemic procalcitonin (PCT) levels were correlated with various clinical parameters. METHODS: PCT levels and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were assessed on the day of sepsis diagnosis in a large series (n = 160) of patients developing sepsis after major visceral surgery. RESULTS: In multivariate analysis, systemic PCT and the APACHE II score could be identified as independent early predictive indicators of lethal sepsis. Combining both indicators at sepsis onset, a prognosis score could be calculated using binary logistic regression analysis allowing the identification of high- and low-risk groups. While 71% of the high-risk patients died of sepsis, 77% of patients assigned to the low-risk group survived the septic complication (sensitivity 71%, specificity 77%). CONCLUSION: Calculation of the prognosis-score allowed for an early prediction of the septic course with high sensitivity and specificity. This information could aid in deciding on adequate treatment strategies.

High-dose aprotinin in cardiac surgery: is high-dose high enough? An analysis of 8281 cardiac surgical patients treated with aprotinin.

In this retrospective analysis we tested the hypothesis that aprotinin doses of more than 6 x 10(6) kallikrein inhibiting units (KIU) per patient may be more effective in reducing bleeding compared with the high-dose regimen of 5-6 x 10(6) KIU aprotinin. The aprotinin doses administered for 8281 adult cardiac surgical patients were correlated to body weight and time of operation and calculated in KIU per kg body weight and minute of operation. Linear and logistic regression models were designed to detect potential associations between dose and postoperative bleeding, transfusion, and other covariates. The 6-h chest tube drainage in the lowest quartile dosing group was 447 +/- 319 mL (mean +/- sd) compared with 360 +/- 290 mL in the highest quartile dosing group (P < 0.001). The proportion of patients requiring allogeneic blood transfusion was reduced from 55% to 47% comparing the lowest with the highest dosing group (P < 0.01). Aprotinin dose was also an independent predictor for rethoracotomy for surgical hemostasis (1.9% in the highest quartile to 2.4% in the lowest dosing quartile; P < 0.01). The risk of renal failure requiring dialysis (2.3% in the highest dosing group vs 3.3% in the lowest dosing group; P < 0.01) or impairment of renal function (creatinine increase of >or=2 mg/dL postoperatively, 6.4% in the highest dosing group vs 10.0% in the lowest dosing group; P < 0.01) was lower with higher doses of aprotinin. Thus, there was no association between aprotinin dose and renal function. Our results support the hypothesis that a more individualized aprotinin regimen with potentially higher doses may optimize the effectiveness of aprotinin therapy in cardiac surgery.

FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer.

PURPOSE: A recent study presented first evidence that a single nucleotide polymorphism (SNP) at codon 388 of fibroblast growth factor receptor 4 (FGFR4) gene, causing a transmembrane domain missense mutation (Gly388Arg), is associated with disease outcome in node-positive breast cancer. This article addresses the clinical relevance of this SNP, FGFR4 genotype, phenotype, and HER2 regarding patient outcome and influence of adjuvant systemic therapy in a substantial primary breast cancer collective (n = 372; median follow-up, 94.5 months). METHODS: Polymerase chain reaction restriction fragment length polymorphism analysis of germ-line polymorphism was performed in uninvolved lymph nodes; FGFR4 and HER2 expression were assessed immunohistochemically in tissue microarrays. RESULTS: In 51% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between FGFR4 genotype and expression or HER2 status. In node-negative patients, FGFR4 genotype was not correlated with disease outcome. In node-positive patients, however, FGFR4 Arg388 was significantly associated with poor disease-free survival (DFS; P = .02) and overall survival (OS; P = .04). Notably, this association seems to be attributable to relatively poor therapy response in Arg388 carriers, reflected in their significantly shorter DFS (P = .02) and OS (P = .045) among patients receiving adjuvant systemic therapy. It is also seen as a significant interaction term in a multivariate proportional hazards model with Arg388 carriers having only about half as much benefit from adjuvant systemic therapy as wild-type carriers. CONCLUSION: According to this study, FGFR4 Arg388 genotype is a marker for breast cancer progression in patients with adjuvant systemic therapy, particularly chemotherapy, and thus may indicate therapy resistance.