The influence of PTEN protein expression on disease outcome in premenopausal hormone receptor-positive early breast cancer patients treated with adjuvant ovarian ablation: a long-term follow-up.

PURPOSE: All breast cancer (BC) patients with detectable hormone receptors (HR) expression should be offered endocrine therapy (ET). In premenopausal patients, tamoxifen and/or ovarian suppression (OvS)/ablation (OA) may improve disease outcome. Alteration of phosphatase and tensin homolog (PTEN) signaling pathways could be one of the possible mechanisms of resistance to antiestrogen therapy. The purpose of this study was to investigate the association of PTEN protein expression with prognostic factors such as tumor histology and grade, estrogen receptor (ER) and progesterone receptor (PgR) status, human epidermal growth factor receptor 2 (HER2) and disease outcome in premenopausal patients with HR-positive early BCs treated with adjuvant OA. METHODS: We analyzed a group of premenopausal early stages I/II HR-positive BC patients who had undergone radical mastectomy followed only with adjuvant OA by irradiation. ER and PgR contents were determined by classical biochemical dextran-coated charcoal (DCC) method, HER2 status by chromogen in situ hybridization (CISH) analysis and PTEN status by immunohistochemistry (IHC). RESULTS: Sixty-six premenopausal patients included into this analysis were followed for a median of 17 years (range 17-29). Compared to PTEN-positive BCs, PTEN-negative BCs were significantly more frequently associated with lobular tumor histology (p<0.05), higher ER content (p<0.05), and had significantly decreased disease-free survival (DFS) and overall survival (OS) (p<0.01 for both) compared to patients with PTEN-positive BCs. CONCLUSIONS: It seems that PTEN status determined by protein expression may discriminate between subgroups with poor and good prognosis in premenopausal HR-positive BC patients receiving adjuvant OA.

Curative intent for unresectable advanced squamous cell esophageal cancer: Overall survival after chemoradiation.

PURPOSE: To analyse the overall survival (OS) of patients with locally advanced, unresectable esophageal cancer treated with chemoradiation (CRT) with or without surgery. METHODS: CRT was administered to 63 patients with locally advanced (T3-4, N0-1), initially unresectable squamous cell esophageal cancer. After the assessment of tumor response to treatment, medically fit patients converted to operable stage were subjected to surgery. Regular follow-up was performed every 3 months during first 2 years, and then every 6 months. RESULTS: All 63 patients completed the whole radiotherapy course. Forty patients (63%) received complete 4 cycles of chemotherapy. In the remaining 23 patients (37%) chemotherapy was interrupted due to toxicity. Clinical response to CRT was: complete response (CR) in 4 patients (6%), partial response (PR in 27 (43%), stable disease (SD) in 22 (35%) patients, and 10 patients (16%) had disease progression (PD). After reevaluation, 23 patients (15 PR and 8 SD after CRT) underwent surgery (37%), all with R0 resection. OS in the whole group was 53% at one year, and 36% at two years. OS was significantly better in the operated group of patients than in the non-operated group. No statistically significant difference in OS was observed comparing operated to CR patients with no surgery (70 vs 50%). In the non-operated group of patients there was no difference in OS between CR, PR, and SD patients. CONCLUSIONS: With appropriate selection, patients with advanced squamous cell esophageal cancer should be considered for potentially effective treatment.

Tumor response and patient outcome after preoperative radiotherapy in locally advanced non-inflammatory breast cancer patients.

PURPOSE: The purpose of this analysis was to assess the tumor response and long-term outcome in patients treated with preoperative radiotherapy (PRT) without systemic therapy. METHODS: Between 1997 and 2000, 134 patients with non-inflammatory locally advanced breast cancer (LABC) were treated with PRT. The tumor dose was 45 Gy in 15 fractions to the breast and to regional lymph nodes over 6 weeks. Radical mastectomy was performed 6 weeks after PRT to all patients and adjuvant systemic therapy was administered as per protocol. The measures of disease outcome were overall survival (OS) and disease-free survival (DFS) which estimated using the Kaplan-Meier method. RESULTS: Median follow-up was 74 months (range 4-216). Objective clinical tumor response after PRT was observed in 77.6% of the patients. Clinical complete tumor response (cCR) was achieved in 21.6% of the patients. Pathological CR in the breast was achieved in 15% of the patients. The 5- and 10-year OS were 55.1 and 37.8%, respectively. The 5- and 10-year DFS were 39.2 and 27%, respectively. Patients who achieved cCR had significantly longer OS in comparison with patients achieving clinical partial response (cPR) and clinical stable disease (cSD). Similarly, DFS of patients in the cCR group was longer compared with patients with cPR and cSD, yet without statistical significance. CONCLUSIONS: Our results showed that local control in LABC patients achieved by primary PRT, followed by radical mastectomy was comparable with the results reported in the literature. Complete pathologic response to PRT identified a subgroup of patients with a trend toward better DFS and OS.

Vaginal packing volume impact on dose parameters during radiography and computed tomography based postoperative brachytherapy of cervical carcinoma.

PURPOSE: To investigate the influence of the vaginal packing volume on the registered dose parameters evaluated by radiography (2D) and computed tomography (CT) (3D) based brachytherapy planning in cervical cancer patients treated with postoperative radiotherapy. METHODS: The postoperative radiotherapy was performed in 40 cervical cancer patients with increased risk for disease relapse. Both, radiography and CT based brachytherapy planning were done in all patients. Vaginal packing volume was evaluated by clinical target volume (CTV)uk, assessed on CT scans and analyzed according to the registered dose parameters: doses delivered to the organs at risk (OAR) and the defined CTV, using both planning methods. RESULTS: CTVuk volume had statistically significant influence on CTV coverage with the prescribed brachytherapy doses D90 (p<0.01) and D100 (p<0.01), revealing a CTVuk cut-off value of 25.6 cm3. Dividing the patients into two groups according to the cutoff value, we found a statistical significance in the registered doses to the rectal wall and no significance in the bladder wall doses between the groups. Also, a statistically significant, negative correlation was found between CTVuk and following doses: Rmax (rho= -0.34, p<0.05), D0.1cc (rho= -0.76, p<0.01), D1cc (rho= -0.74, p<0.01) and D2cc (rho= -0.72, p<0.01), D90 (rho= -0.80, p<0.01), D100 (rho= -0.7, p<0.01). CONCLUSION: If the brachytherapy vaginal packing is of a large volume (more than 25.6 cm3), an asymmetric deformation of the proximal part of the vaginal cavity might appear, leading to inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a vaginal packing volume larger than 25.6 cm3 made no further reduction in the bladder dose, but it made a statistically significant further reduction in the rectal doses.

p21 does, but p53 does not predict pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) is the standard treatment option in locally advanced rectal cancer. The tumor response is assessed through tumor and nodal downstaging and the tumor regression grade. Currently, there is no method to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53 expressions could be a reliable predictors of pathological response to CRT. METHODS: Fifty patients with locally advanced rectal cancer were treated with preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53 immumohistochemical staining was performed on pretreatment biopsies and the results were compared with tumor regression according to grading systems by Dworak (TRG grades) and by Wheeler (RCRG grades). RESULTS: Testing RCRG grades in relation to p21 expression showed statistically significant difference (p=0.021). RCRG 3 (poor response) was more frequent in the group of patients with low p21. According to Dworak, grade 4 (complete regression) was more frequent in the group of patients with positive p21 expression (p=0.032). Significant difference in p21 expression in grade 4 group compared with all other grade groups was also found (p=0.007). Patients with immune expression of p21 had significantly higher percentage of complete regression in comparison to the patients with low expression of p21. We haven't found any correlation between p53 expression and histopathological (HP) as well as regression grades. CONCLUSION: According to both grading systems, our results suggest that p53 expression does not, but p21 expression does predict pathological response to preoperative CRT.

Does the computed tomography perfusion imaging improve the diagnostic accuracy in the response evaluation of esophageal carcinoma to the neoadjuvant chemoradiotherapy? Preliminary study.

PURPOSE: To estimate whether the computed tomography (CT) perfusion imaging could be useful to predict the pathological complete response (pCR) of esophageal cancer to the neoadjuvant chemoradiotherapy (NACRT). METHODS: Twenty-seven patients with the advanced squamous cell esophageal carcinoma, who were treated with concomitant CRT (CIS/5-FU/LV and 45-50 Gy total radiation dose), were re-evaluated using CT examination, which included the low-dose CT perfusion study. CT perfusion series were analysed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE), and color parametric maps of the blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) were displayed. All patients were operated and histopathological analysis of the resected esophagus considered the gold standard for pathologic complete response (pCR). RESULTS: BFpost-NACRT, BVpost-NACRT, and PSpost-NACRT were significantly lower, and MTTpost-NACRT significantly higher in the pCR group. Mean (±SD), or median perfusion parameter values in the pCRs (11 patients) vs non-pCRs (16 patients) were: BFpost-NACRT- 21.4±5.0 vs 86.0±29 ml/min/100 g (p<0.001), BVpost-NACRT- 1.3 vs 3.9 ml/100 g (p<0.001), MTTpost-NACRT- 5.5 vs 3.7 s (p=0.018), and PSpost-NACRT- 5.9 vs 9.8 ml/min/100 g (p=0.006). ROC analysis revealed that BFpost- NACRT (AUC=1.000), BVpost-NACRT (AUC=0.932), MTTpost-NACRT (AUC=0.801), and PSpost-NACRT (AUC=0.844) could predict the pCR (p<0.01), while maximal esophageal wall thickness could not (AUC=0.676, p=0.126). If we set a cut-off value of BFpost-NACRT<30.0 ml/min/100 g, pCR was predicted with sensitivity and specificity of 100%. CONCLUSION: CT perfusion imaging enables accurate prediction of pCR of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients.

PURPOSE: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. METHODS: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. RESULTS: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. CONCLUSION: Taken together, our results, showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression, detected by Western blotting, could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients.

3D MRI-based evaluation of the 2D brachytherapy planning in patients with advanced cervical cancer: An analysis of the delivered dose.

PURPOSE: To analyze the dose distribution achieved during 2D radiography-based brachytherapy (BRT) planning, by using a 3D MRI-based BRT replanning evaluation, in patients with advanced cervical carcinoma, treated with definitive concomitant chemoradiation (CCRT). METHODS: The curative CCRT was applied to 30 patients with advanced cervical carcinoma. For each patient, 2D radiography-based planning and a 3D MRI-based BRT replanning were performed. Applying the same source positions and dwell times in both planning methods, it was possible to use the MRI replanning to evaluate the dose distribution, maximum organs at risk (OAR) doses and target volume coverage, that was obtained during 2D BRT planning. RESULTS: A statistically significant difference for bladder and rectum maximum doses, between 2D planning (Bmax, Rmax) and 3D replanning (D0.1ccm, D1ccm, D2ccm) was found, except between Bmax and bladder D2ccm dose (p=0.07), and Rmax and rectal D2ccm dose in the group of patients with symmetrical rectum position regarding the applicator system (p=0.47). MRI evaluation of the HR-CTV volume, according to the 2D planning achieved dose distribution, revealed total EQD2 HR-CTV doses: D90 (107.15±22.06 Gy) and D100 (80.66±14.58 Gy). CONCLUSION: 2D radiography-based BRT planning can provide a good estimation for the bladder and rectum 3D D2ccm dose with a significant statistical difference for the doses in the smaller OAR volumes (D0.1ccm, D1ccm). Inability to visualize tumor tissue during 2D BRT planning provides no option in tailoring the dose distribution to the tumor volume and patient anatomy, leading to potential under/over-treatment in some patients.

Implementation of intensity-modulated radiotherapy and comparison with three-dimensional conformal radiotherapy in the postoperative treatment of cervical cancer.

PURPOSE: Within implementation of intensity-modulated radiotherapy (IMRT) in the postoperative irradiation of cervical cancer we evaluated and compared IMRT and three-dimensional conformal radiotherapy (3DCRT) dosimetric parameters for target volumes and organs at risk (OAR). METHODS: We randomized 95 patients with cervical cancer, UICC stage I-III, in groups depending of the type of external beam postoperative radiotherapy. Forty-five patients were treated with IMRT and 50 with 3DCRT. All patients underwent brachytherapy, and according to risk factors some of the patients had concomitant cisplatin chemotherapy. The study was done in a period of three years from December 2015. Analysis of dosimetric parameters for target volume coverage and OARs was performed. RESULTS: IMRT plans showed better conformity compared to 3DCRT plans, represented with homogenity index and conformity index, with higher maximum dose (PTV105 and D2). Both plans achieved adequate planning target volume coverage described with PTV95. Statistically significant difference between groups was found for bladder, rectum and bowel high dose regions: bladder V45 (p=0.000), rectum V40 (p=0.043) and V45 (p=0.000), bowel V45 (p=0.000), and bone marrow dosimetric parameters V20-V45; all were better in IMRT plans. Significant difference was found for volume of patient body normal tissue receiving dose of 20Gy, which was higher in IMRT. CONCLUSION: IMRT is a highly conformal technique. Satisfactory target volume coverage was achieved with both techniques, with better sparing of OARs in the IMRT group. With this technique improvement, we expect better quality of life in cervical cancer patients with good prognosis.

Acute toxicity of postoperative intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cervical cancer: The role of concomitant chemotherapy.

PURPOSE: The toxicity of postoperative radiotherapy for cervical cancer affects patients' quality of life. We evaluated acute toxicity in postoperative intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) as well as the influence of dosimetric parameters and concomitant chemotherapy. METHODS: A total of 45 patients with early operable cervical cancer underwent postoperative IMRT with 40-45 Gy. The control group of 50 patients was treated with 3DCRT. Brachytherapy and concomitant cisplatin chemotherapy were performed in all patients according to pathologic and histologic findings. The patients were monitored for acute gastrointestinal, urological and hematological toxicity classified according to the RTOG acute radiation morbidity scoring criteria. We also analyzed the influence of dosimetric parameters on acute toxicity. RESULTS: Significant differences were found in overall acute toxicity (p=0.018), acute genitourinary toxicity (p=0.029), anemia (p=0.043) and neutropenia (p=0.027) but not in acute gastrointestinal toxicity between the IMRT and 3DCRT groups. In all patients, regarding chemotherapy administration, differences were found between the chemoradiotherapy and radiotherapy group as far as overall acute toxicity (CHRT vs RT; p=0.011) and hematological toxicity were concerned (p=0.001). Patients with ≥3 cycles of chemotherapy showed increased hematologic toxicity. In the IMRT group according to the administration of chemotherapy (chemoradiotherapy vs radiotherapy), statistically significant difference for leukopenia (p=0.009) was found and in the 3DCRT group for anemia (p=0.021) and neutropenia (p=0.029). According to chemotherapy administration (chemoradiotherapy vs radiotherapy), a statistically significant difference in leukopenia (p=0.009) was found in the IMRT group while in the 3DCRT group the differences were in anemia (p=0.021) and neutropenia (p=0.029). CONCLUSION: IMRT is associated with lower acute toxicity and better dosimetric parameters in organs at risk (OAR) compared to 3DCRT. Higher hematological toxicity occurred when concomitant chemotherapy was performed, regardless of RT technique. Further reduction of toxicity is expected with protocol and technical improvement and research of gene-related toxicity.

pSTAT3 expression associated with survival and mammographic density of breast cancer patients.

BACKGROUND: Constitutive activation of STAT3 have been shown in several tumor types including breast cancer. We investigate STAT3 expresion as possible molecular marker for breast cancer early detection, as well as prognostic factor for determination of tumor agressiveness. METHODS: In this study we measure p(Y705)STAT3 expression in tumor and adjacent tissue of breast cancer patients by Western blot. For relapse-free survival (RFS) and overall survival (OS) we used Log-Rank test. RESULTS: We show that average expression of p (Y705) STAT3 in tumor tissue is higher compared to adjacent tissue. Moreover, we found that patients with HER2 positive receptors had significantly higher pSTAT3 expression compared to HER2 negative patients. We showed that patients with high mammographic density had significantly higher tumor expression of pSTAT3 compared to patients with low mammographic density. Also, we show that pSTAT3 expression correlates with longer RFS in the entire group of patients, as well as in the group of ER positive, in lymph node positive and in older group of breast cancer patients (with age over 50). Furthermore, in the entire group of patients, in ER positive, in lymph node positive and in older group of patient, high expression of pSTAT3 showed a better survival than low expression of pSTAT3. CONCLUSION: Considering that the expression of pSTAT3 is associated with longer RFS and survival, it can be used as prognostic tools for determination of group of breast cancer patients with low-risk.

Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer.

BACKGROUND: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity. METHODS: The study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%). RESULTS: We identified 192 significantly differentially expressed genes (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to regulation of cellular development, growth and proliferation, cell cycle control of chromosomal replication, glucose metabolism and NAD biosynthesis II route. APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between pRT responders and non-responders in preoperative setting, while MAP3K4 was further validated as RT-specific predictive biomarker of distant metastasis free survival (HR = 2.54, [95%CI:1.42-4.55], p = 0.002) in the postoperative setting. CONCLUSIONS: This study pinpoints MAP3K4 as a putative biomarker of response to RT in both preoperative and postoperative settings and a potential target for radiosensitising combination therapy, warranting further pre-clinical studies and prospective clinical validation.

Follow-Up Imaging of Inflammatory Myofibroblastic Tumor of the Uterus and Its Spontaneous Regression.

Inflammatory myofibroblastic tumor (IMT) is an aggressive benign mass that may arise from various tissues and organs with a great variability of histological and clinical appearances. Due to variable and nonspecific imaging findings, diagnosis of IMT is not obtained before surgery. The aim of this paper is to present CT and MRI findings during four-year follow-up of complete, spontaneous regression of IMT of the uterus. The diagnosis was made by histology and immunohistochemistry analysis of the open excisional biopsy specimen. At that time, the organ of origin was not specified. After analysis of the follow-up imaging findings and the mode of tumor regression, the uterus was proclaimed as the probable site of origin. IMT of the uterus is extremely rare and has been reported in ten cases up to now. The gradual, complete regression of uterine IMT documented by CT and MRI may contribute to understanding of its nature.

Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: ductal carcinoma in situ vs. invasive ductal carcinoma.

OBJECTIVES: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. MATERIALS AND METHODS: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n=30) and IDC (n=30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. RESULTS: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p<0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p<0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p<0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p<0.0001). CONCLUSIONS: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.

[The role of breast magnetic resonance imaging in the diagnosis of ductal carcinoma in situ].

Ductal carcinoma in situ (DCIS), the noninvasive breast malignant tumor originates from the terminal ductal-lobular units (TDLU). The typical feature of DCSI is the formation of calcifications. Up to 90% of DCIS are diagnosed on mammographic examinations, as clinically asymptomatic. Between 10% and 20% of DCIS remain mammographically occult due to the lack of calcifications and/ or small tumor dimensions. Contrast-enhanced breast magnetic resonance imaging (MRI) detects mammographically occult breast lesions, thus defining morphologic features of the lesion and the dynamics of signal intensity changes due to contrast enhancement. Distribution of contrast enhancement - signal intensity increase in DCIS most frequently includes segmental, ductal and linear patterns, followed by regional enhancement pattern, while the intralesional contrast uptake most frequently includes the nodular pattern with the areas of confluence. Postcontrast signal intensity increase in DCIS is most frequently fast in the initial phase (wash-in), while the whole dynamic of contrast-enhancement includes either of the three possible time-intensity curve (TIC) types (persistent, plateau or washout), although the plateau TIC is considered to be more frequent. Breast MRI has high sensitivity in the diagnosis of invasive breast cancer, varying from 90% to 100%; the sensitivity in the diagnosis of DCIS is lower (77-96%). For the time being, the primary role of MRI in DCIS is planning of breast-conserving surgery (BCS) for the evaluation of lesion extension. Further development of MRI in the diagnosis of DCIS includes the implementation of the principles of functional and molecular imaging.

MRI in the evaluation of breast cancer patient response to neoadjuvant chemotherapy: predictive factors for breast conservative surgery.

PURPOSE: We aimed to prospectively assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the evaluation of predictive factors for breast conservative surgery during neoadjuvant chemotherapy. MATERIALS AND METHODS: Sixty-six patients were evaluated before the first treatment cycle, after the second cycle, and upon the completion of neoadjuvant chemotherapy according to largest tumor diameter, tumor volume, postcontrast enhancement, and tumor regression pattern. The patients were divided into responders (pathologic complete and near complete response) and nonresponders. Each subgroup was re-evaluated according to morphokinetic criteria for identification of candidates for breast conservative surgery. RESULTS: In responders (n=27), the lesion size upon the completion of neoadjuvant chemotherapy was significantly smaller compared to nonresponders (1.5 ± 0.6 vs. 3.2 ± 0.9 cm; P < 0.001), as was the volume (1.2 vs. 11.0 cm(3); P < 0.001). The measured lesion size did not differ from the histologic size (1.5 ± 0.6 vs. 1.2 ± 0.6 cm; P = 0.09) and had a high correlation (r=0.93). In responders, the following parameters were significantly different before and after neoadjuvant chemotherapy: size (3.6 ± 1.4 to 1.5 ± 0.6 cm; P < 0.001), volume (17.6 to 1.2 cm(3); P < 0.001), predominant concentric regression, plateau and continuous time-intensity curves (P < 0.001). DCE-MRI has the sensitivity of 87% and the accuracy of 77% to identify candidates for breast conservative surgery. CONCLUSION: Selected morphokinetic DCE-MRI parameters may contribute to the multidisciplinary decision when considering the selection of candidates for breast conservative surgery.

The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients.

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.