Comparison of different motion correction techniques for dynamic FDG-PET/CT studies in breast cancer patients.

BACKGROUND: Our aim was to evaluate interchangeability of different motion correction methods in the assessment of dynamic FDG-PET/CT studies in breast cancer patients as well as to assess the interrater reliability of these methods. METHODS: In our prospective study we included patients with malignant breast tumours. Dynamic PET acquisition lasted for 60 minutes after tracer (FDG) injection. Every study was assessed by the same two experienced observers. We assessed plasma activity noninvasively. In case of the primary tumour VOIs we applied two different approaches to correct motion artefacts: method I) frame-by-frame manual motion correction; method II) frame-by-frame semi-automatic software-based motion correction. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). RESULTS: Thirty-five lesions detected during 34 dynamic studies were included in this current analysis. Interrater reliability of both applied motion correction methods proved to be excellent (ICC=0.89-0.99), except Ki measured by method I (ICC=0.66). Bland-Altman analysis revealed that method II resulted in significantly lower values than method I regarding k3 and Ki in case of both observers, and regarding MRFDG in one of the observers. In case of K1 and k2 the two methods were in good agreement. CONCLUSIONS: Both applied methods proved to be reproducible and reliable, especially method II, where every measured kinetic parameter showed excellent interrater reliability. Different approaches of motion correction could have a significant effect on the results of the kinetic modelling; therefore careful selection of the most reliable method is advised.

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer.

Background: Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer.Methods: One hundred and twenty breast carcinoma cases with residual disease that were treated with one of three types of pre-operative chemotherapy regimens were selected for the study. The percentage of StrTIL was evaluated in pretreatment core biopsies (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL). TIL changes (ΔStrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL.Results: When analyzing the pre-StrTIL and post-StrTIL among the three treatment groups, we detected significant StrTIL increase independently of the treatment applied. Based on distant metastases-free survival analysis, both post-StrTIL and ΔStrTIL was found to be independent prognostic factor in HR negative cases. Conclusions: Significant increase of StrTIL in the residual disease was observed in patients treated with the highly (platinum), moderately (cyclophosphamide) and marginally mutagenic chemotherapeutic agents (taxane, anthracycline). Increase in StrTIL in residual cancer compared to pretreatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.

Defining the design space for freeze-dried orodispersible tablets with meloxicam.

OBJECTIVE: This work focused on simultaneously investigating formulation variables and freeze-drying parameters when preparing orodispersible tablets with meloxicam (Mel), by a Quality by Design (QbD) approach. MATERIALS AND METHODS: Methylcellulose (MC) was selected as a matrix forming agent and mannitol (Man) as cryoprotectant, both at two concentration levels. The freezing regime was also varied between fast and shelf-ramped, to find out how it affects the final products. The tablet formulations were characterized for their disintegration time, wetting properties, mechanical properties, morphology and in vitro dissolution. Response Surface Modeling completed the statistical analysis that assessed the effects of independent variables on the responses. RESULTS: All the responses showed good fitting to the chosen model. The increase in MC content determined a positive effect on disintegration time, wetting time, mechanical strength and a negative effect on Mel dissolution. High levels of Man-determined brittle products with low-absorption capacity and fast Mel dissolution. The freezing rate had an important effect on the structure of tablets: fast freezing determined slightly thicker pore walls with smooth surfaces, while shelf-ramped freezing led to a multiple-layer structure with increased hardness. Still, shelf-ramped freezing yielded higher Mel release, due to physical changes of the active substance during the freeze-drying process. CONCLUSION: From the generated design space, an optimal formulation was obtained and the results validated the experimental design. The QbD approach was an efficient manner of understanding formulation and process parameters at the freeze-dried orodispersible tablets preparation.

Morphological and pathological response in primary systemic therapy of patients with breast cancer and the prediction of disease free survival: a single center observational study.

AIM: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST. METHODS: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US. Prior to PST, tumors were subclassified according to core biopsy (NCB) and/or fine-needle aspiration-based immunohistochemical profiles of NCB. Pathological response rates were assessed following the surgeries by using Chevallier classification. Tumor measurements by PE and US were obtained before and after PST. Different clinical measurements were compared with histological findings. Disease-free survival (DFS) was assessed. RESULTS: Pathological complete remission (pCR=Chevallier I/II) was observed in 25 patients (21.5%), 44% of whom had triple negative histology, 28% Her2 positive and 76% had high-grade tumor. Of 116 patients, 24 received taxane-based PST, 48 combined taxane + anthracycline treatment, 8 trastuzumab combinations, 21 anthracycline-based treatments, and 15 other treatments. In the taxane treated group, the pCR rate was 30%, in the taxane + anthracycline group 25%, in the anthracycline group 9.5%, and in trastuzumab group 37.5%. After PST, PE and US were both significantly associated with pathology (P<0.001 and P=0.004, respectively). Concerning OS, significant difference was observed between the Chevallier III and IV group (P=0.031) in favor of Chevallier III group. In the pCR group, fewer events were observed during the follow-up period. CONCLUSIONS: Our results show that even limited, routinely used immunohistochemical profiling of tumors can predict the likelihood of pCR to PST: patients with triple negative and Her2-positive cancers are more likely to achieve pCR to PST. Also, PE is better correlated with pathological findings than US.

Response evaluation after primary systemic therapy of Her2 positive breast cancer ­ an observational cross-sectional study.

AIM: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. METHODS: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). CONCLUSION: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

[Monoclonal antibody therapy in breast cancer]. / Monoklonális antitest-terápia emlõrákban.

A new trend has been taking place in the daily oncology practice in the past twenty years: we are progressively moving toward individualized and personalized treatments. The treatment of breast cancer is one of the best examples to underline the outstanding effectiveness of the individualized approach. The modern molecular pathology features are capable of predicting the biological behavior of the tumors which gives a new basis for our therapeutic choices, both for neoadjuvant and adjuvant settings, as well as for metastatic disease. In our paper we review the currently used monoclonal antibodies in the treatment of breast cancer and provide an overview of the new research and future directions in this field.

[The role of FDG-PET-CT in the evaluation of primary systemic therapy in breast cancer: links between metabolic and pathological remission]. / Az FDG-PET-CT szerepe az emlorák primer szisztémás kezelése során: a metabolikus változások és a patológiai remisszió összefüggései.

INTRODUCTION: FDG-PET-CT is highly sensitive in detection of viable tumour tissue, giving an importance for that in oncological diagnostics. AIM: The authors analysed retrospectively the relationship between metabolic response and changes in Ki-67, a proliferation marker. METHODS: Staging FDG-PET-CT scans (before and after therapy) SUVs (Standardized Uptake Value), and morphological changes in the primary tumour and axillary lymph node region were evaluated in 30 patients with breast cancer. Calculated ΔSUV were compared with Ki-67 proliferation marker (measured in biopsies and surgical specimens). RESULTS: The decrease of SUV and size were significant in the primary tumour and the axillary lymph node region. Decrease of Ki-67 was significant. Significant correlation was found between Ki-67 and SUV before therapy, initial Ki-67 and ΔSUV, and ΔKi-67 and ΔSUV. CONCLUSIONS: The metabolic changes were more sensitive in the measurement of the therapeutic response than morphological remission, and they correlated well with the pathological response, in not standardized clinical conditions even.

Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes.

We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4+/CD8+ positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4+/CD8+ ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression.

Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations.

Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients' informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively. To delineate primary tumors we applied a frame-by-frame semi-automatic software-based correction of motion artefacts. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). We found that k3, Ki and MRFDG were significantly higher in higher grade (p = 0.0246, 0.0089 and 0.0076, respectively), progesterone-receptor negative (p = 0.0344, 0.0217 and 0.0132) and highly-proliferating (p = 0.0414, 0.0193 and 0.0271) tumors as well as in triple-negative and hormone-receptor negative/HER2-positive subtypes (p = 0.0310, 0.0280 and 0.0186). Ki and MRFDG were significantly higher in estrogen-receptor negative tumors (p = 0.0300 and 0.0247, respectively). Ki was significantly higher in node-positive than in node-negative disease (p = 0.0315). None of the assessed FDG-kinetic parameters showed significant correlation with stromal TIL. In conclusion, we confirmed a significant relationship between kinetic parameters measured by dynamic PET and the routinely assessed clinicopathological factors of breast cancer: high-grade, hormone-receptor negative tumors with high proliferation rate are characterized by higher cellular FDG-uptake and FDG-phosphorylation rate. Furthermore, we found that kinetic parameters based on the dynamic examinations are probably not influenced by stromal TIL infiltration.

Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer.

We aimed to analyze the expression of cell-cycle regulation markers - minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) - in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (p < 0.01 and p < 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (p = 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.

Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

OBJECTIVES: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. METHODS: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. RESULTS: A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p < 0.001) and tumor size (p < 0.001) regarding the primary breast lesions. To predict pCR, Method 2 had higher sensitivity (72.4 % vs. 44.8 %) and negative predictive value (57.9 % vs. 45.8 %) with lower false negativity rate (16 vs. 32) than Method 1. pCR rate was higher in Her2-positive and triple negative tumors. Despite the significant differences detected between the biological subtypes regarding changes in primary tumor SUVmax (p = 0.007) and size (p = 0.015), the subtypes only had significant impact on response evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. CONCLUSIONS: Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.

Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain. METHODS: One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier curve estimation, log-rank test and cox regression analysis were carried out to reveal the association between Ki-67 categories and survival (DMFS = Distant metastases-free survival, OS = Overall survival). RESULTS: Twenty three out of 120 patients (19.2%) achieved pathologic complete remission (pCR), whereas partial remission (pPR) and no response (pNR) to neoadjuvant chemotherapy (NAC) was detected in 60.8% and 20.0%, respectively. The distribution of subtypes showed a significant difference in pathological response groups (p < 0.001). Most of the TNBC cases were represented in pCR group. The most relevant cut-off value for the Ki-67 distinguishing pCR from pNR cases was 20% (p = 0.002). No significant threshold for Ki-67 was found regarding DMFS (p = 0.208). Considering OS, the optimal cut-off point occurred at 15% Ki-67 (p = 0.006). The pPR group represented a significant Ki-67 threshold at 30% regarding OS (p = 0.001). Ki-67 and pPR subgroups were not significantly associated (p = 0.653). For prognosis prediction, Ki-67 at 30% cut-off value (p = 0.040) furthermore subtype (p = 0.037) as well as pathological response (p = 0.044) were suitable to separate patients into good and unfavorable prognosis cohorts regarding OS. However, in multivariate analyses, only Ki-67 at 30% threshold (p = 0.029), and subtype (p = 0.008) were independently linked to OS. CONCLUSIONS: NAC is more efficient in tumors with at least 20% Ki-67 LI. Both Ki-67 LI and subtype showed a significant association with pathological response. Ki-67 LI represented independent prognostic potential to OS in our neoadjuvant patient cohort, while pathological response did not. Additionally, our data also suggest that if a tumor is non-responder to NAC, increased Ki-67 is a poor prognostic marker.

Expression of cell cycle markers is predictive of the response to primary systemic therapy of locally advanced breast cancer.

We aimed to analyze to what extent expression of four cell cycle regulation markers-minichromosome maintenance protein (MCM2), Ki-67, cyclin A, and phosphohistone-H3 (PHH3)-predict response to primary systemic therapy in terms of pathological complete remission (pCR). In search of an accurate and reproducible scoring method, we compared computer-assisted (CA) and routine visual assessment (VA) of immunoreactivity. We included 57 patients with breast cancer in the study. The cell cycle markers were detected using immunohistochemistry on pre-therapy core biopsy samples. Parallel CA (validated by manual labeling) and standard VA were performed and compared for diagnostic agreement and predictive value for pCR. CA and VA results were dichotomized based on receiver operating characteristic analysis defined optimal cut-off values. "High" was defined by staining scores above the optimal cut-off, while "low" had staining scores below the optimal cut-off. The CA method resulted in significantly lower values for Ki-67 and MCM2 compared to VA (mean difference, -3.939 and -4.323). Diagnostic agreement was highest for cyclin A and PHH3 (-0.586 and -0.666, respectively). Regardless of the method (CA/VA) used, all tested markers were predictive of pCR. Optimal cut-off-based dichotomization improved diagnostic agreement between the CA and VA methods for every marker, in particular for MCM2 (κ = 1, p < 0.000). Cyclin A displayed excellent agreement (κ = 0.925; p < 0.000), while Ki-67 and PHH3 showed good agreement (κ = 0.789, p < 0.000 and κ = 0.794, p < 0.000, respectively). We found all cell cycle markers (Ki-67, MCM2, cyclin A, and PHH3) predictive of pCR. Diagnostic agreement between CA and VA was better at lower staining scores but improved after optimal cut-off-based dichotomization.

AXL-associated tumor inflammation as a poor prognostic signature in chemotherapy-treated triple-negative breast cancer patients.

A subgroup of triple-negative breast cancer (TNBC) shows epithelial-to-mesenchymal transition (EMT) features, which are sustained by the interaction between cancer cells and tumor-associated macrophages (TAMs). In this study, the clinical relevance of 30 EMT-related kinases and the potential cross-talk with TAMs were investigated in a cohort of 203 TNBC patients treated with adjuvant chemotherapy. The prognostic value of the evaluated markers was validated in two independent cohorts of TNBC patients treated with adjuvant chemotherapy (N=95; N=137). In vitro, we investigated the potential synergism between cancer cells and TAMs. We found that the EMT-related kinase AXL showed the highest correlation with the frequency of CD163-positive macrophages (rS=0.503; P<0.0001). Relapsing TNBC patients presented high expression of AXL (P<0.0001) and CD163 (P<0.018), but only AXL retained independent prognostic significance in multivariate analysis (relapse-free survival, P=0.002; overall survival P=0.001). In vitro analysis demonstrated that AXL-expressing TNBC cells were able to polarize human macrophages towards an M2-like phenotype, and modulate a specific pattern of pro-tumor cytokines and chemokines. Selective AXL inhibition impaired the activity of M2-like macrophages, reducing cancer cell invasiveness, and restoring the sensitivity of breast cancer cells to chemotherapeutic drugs. These data suggest that the EMT-related kinase AXL overexpressed in cancer cells has prognostic significance, and contributes to the functional skewing of macrophage functions in TNBC. AXL inhibition may represent a novel strategy to target cancer cells, as well as tumor-promoting TAMs in TNBC.

Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer.

OBJECTIVE: The aim of this study was to observe the relationships between different metabolic parameters and clinicopathological features (CPFs) or immunohistochemically defined biological subtypes (IHC-BS) in breast cancer. MATERIALS AND METHODS: Eighty-two women (83 lesions, tumour size>15 mm) underwent PET/computed tomography imaging after a core biopsy. Maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in the primary tumour were calculated and compared with CPFs and IHC-BS. Tumours with oestrogen receptor (ER) positivity were separately investigated in relation to their progesterone receptor (PR) status. RESULTS: Significant correlation was found between all metabolic parameters and high nuclear grade or ER status or IHC-BS. All parameters were higher in PR(-) and triple-negative cases than in PR(+) and non-triple-negative tumours, and the correlation was significant for most of the metabolic parameters (except for SUVavg in the case of PR status and MTV in the case of triple negativity). Significant correlation was found only for SUVmax regarding the human epidermal growth factor receptor 2 (HER2) status. There was moderate correlation between the Ki67 expression and the SUVmax or SUVavg. All metabolic parameters were higher in ER(+)/PR(-)/HER2(-) lesions compared with ER(+)/PR(+)/HER2(-) cancers. However, ER(+)/PR(-)/HER2(+) tumours had lower SUVmax and SUVavg compared with ER(+)/PR(+)/HER2(+) lesions. CONCLUSION: Our study confirms that the fluorine-18 fluorodeoxyglucose uptake in primary tumour is associated with distinct CPFs or IHC-BS in breast cancer. SUVmax may reflect tumour metabolism more reliably compared with SUVavg, MTV or total lesion glycolysis. Our preliminary results suggest different biological properties in ER(+) tumours with different PR statuses.

Complexity of Response Evaluation During Primary Systemic Therapy of Breast Cancer: Scoring Systems and Beyond-Preliminary Results.

BACKGROUND: Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST). PATIENTS AND METHODS: Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI). In parallel response assessment was performed by European Organization for Research and Treatment of Cancer (EORTC); PET Response Criteria in Solid Tumors (PERCIST); World Health Organization (WHO); Response Evaluation Criteria in Solid Tumors (RECIST); Chevallier and Sataloff classifications, and by a novel Ki-67 score. Accuracy of different scoring systems was evaluated. RESULTS: In the 42 enrolled patients, SUVmax, size, and Ki-67 LI decreased significantly on PST. Significant differences between patients with versus those without pathological complete response were observed for pre-treatment Ki-67 LI and SUVmax and for post-treatment Ki-67 LI, SUVmax and size. Change in Ki-67 LI was the best predictor of pathological complete response. Correlation patterns of the directly measured metabolic, morphological, and proliferation responses differed from those determined by scoring methods. CONCLUSION: During PST, FDG-PET/CT enables for robust assessment of treatment efficacy, but more reliable scoring systems are still needed for more precise response evaluation.

Primary systemic therapy for breast cancer: Does the patient's involvement in decision-making create a new future?

OBJECTIVE: Primary systemic therapy (PST) followed by surgery is the standard initial treatment for locally advanced breast cancer (LABC). However, some patients are averse to mastectomy or breast-conserving surgery and do not consent to these procedures. The reasons for this controversial decision, the factors influencing the decision-making and optimal solutions for decision aiding need to be investigated. METHODS: We addressed these questions by a review of literature on the possibilities associated with different patient choices and subsequent treatment options in relation to LABC. RESULTS: A total of 5 reviews and 22 clinical studies were summarized in relation to decision making and the most successful decision aids. A discussion is given of the issues of those few patients who cannot be convinced to undergo surgery. CONCLUSION: Currently there is no guideline for the treatment of patients who reject the surgical procedures after PST. Medical oncologists should be able to apply decision aid modalities in a personalized manner to give all needed information to their patients thereby ensuring a deliberate decision-making process, facilitating acceptance of a need for surgery, and thus improving the chances of prolonged survival. PRACTICE IMPLICATIONS: Currently multidisciplinary tumor boards are the most suitable decision aids in oncological practice.