Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer.

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.

Long term improved quality of life by a 2-week group physical and educational intervention shortly after breast cancer chemotherapy completion. Results of the 'Programme of Accompanying women after breast Cancer treatment completion in Thermal resorts' (PACThe) randomised clinical trial of 251 patients.

BACKGROUND: Quality of life (QoL) after breast cancer is nowadays a major challenge. Complementary interventions are necessary because of frequent depression symptoms after treatment and also to favour return to activity. Besides, radio-chemotherapy has side-effects like weight gain and fatigue. Several strategies including group behavioural-educational interventions, physical training and/or dietary education, have been tested to answer these difficulties with moderate success in the long run. METHODS: Two hundred and fifty-one non-metastatic patients were accrued after chemotherapy in a prospective randomised multicenter trial between 2008 and 2010, testing a 2-week intervention in SPA centres. Intervention comprised group physical training, dietary education and physiotherapy. Selected patients were in complete remission. QoL was evaluated with SF36 questionnaire, anxiety and depression with the hospital anxiety and depression (HAD) one. Anthropometric measures and QoL evaluations were obtained before randomisation and every 6 months during 3 years. RESULTS: Two hundred and twenty patients were evaluable at 1 year. Intervention increased SF36 score by 9.5 points (p=0.000006), 4.6 (p=0.032) and 6.2 (p=0.028) respectively at 6, 12 and 24 months. Effect size (ES) was 0.63 [0.37; 0.90], 0.29 [0.03; 0.55] and 0.41 [0.04; 0.78]. Anxiety score was shortly minored by intervention (6-month ES=-0.24 [-0.42; -0.05]) and depression score more durably: ES=-0.45 [-0.72; -0.18], -0.34 [-061; -0.08], and -0.26 [-0.63; 0.11] at 6, 12 and 24 months. CONCLUSION: This 2-week group intervention seemed to durably influence QoL of breast cancer patients treated by chemotherapy. Differences, smaller at 12 months than at six, suggest that a second but shorter intervention could help maintain the 6-month benefits.

[Analysis of gene expression data regulated by clock-genes: methodological approach and optimization]. / Analyse de données d'expression transcriptomiques rythmées par des gènes-horloge: approche méthodologique et optimisation.

BACKGROUND: In microarray data, wide-scale correlations are numerous and increase the number of genes correlated to a test condition (phenotype, mutation status, etc.) either positively or negatively. Several methods have been developed to limit the effect of such correlations on the false discovery rate, but these may reject too many genes that have a mild or indirect impact on the studied condition. We propose here a simple methodology to correct this spurious effect without eliminating weak but true correlations. RESULTS: This methodology was applied to a microarray dataset designed to distinguish heterozygous BRCA1 mutation carriers from non-carriers. As our samples were collected at different times in the morning, we evaluated the effect of correlations due to circadian rhythm. The circadian system is a well-known correlation network, regulated by a small number of period genes whose expression varies throughout the day in predictable ways. The downstream effects of this variation on the expression of other genes, however, are incompletely characterized. We used two different strategies to correct this correlation bias, by either dividing or multiplying the expression of correlated genes by the expression of the considered period gene according to the sign of the correlation between the period gene and correlated gene (respectively positive or negative). CONCLUSIONS: We observed a linear relationship between the number of false-positive/negative genes and the strength of the correlation of the candidate gene to the test condition. BRCA1 was highly correlated to the period gene Per1; our correction methodology enabled us to recover genes coding for BRCA1-interacting proteins which were not selected in the initial direct analysis. This methodology may be valuable for other studies and can be applied very easily in case of well-known correlation networks.

Rare germline large rearrangements in the BRCA1/2 genes and eight candidate genes in 472 patients with breast cancer predisposition.

Hereditary breast cancers account for up to 5-10 % of breast cancers and a majority are related to the BRCA1 and BRCA2 genes. However, many families with breast cancer predisposition do not carry any known mutations for BRCA1 and BRCA2 genes. We explored the incidence of rare large rearrangements in the coding, noncoding and flanking regions of BRCA1/2 and in eight other candidate genes--CHEK2, BARD1, ATM, RAD50, RAD51, BRIP1, RAP80 and PALB2. A dedicated zoom-in CGH-array was applied to screen for rearrangements in 472 unrelated French individuals from breast-ovarian cancer families that were being followed in eight French oncogenetic laboratories. No new rearrangement was found neither in the genomic regions of BRCA1/2 nor in candidate genes, except for the CHEK2 and BARD1 genes. Three heterozygous deletions were detected in the 5' and 3' flanking regions of BRCA1. One large deletion introducing a frameshift was identified in the CHEK2 gene in two families and one heterozygous deletion was detected within an intron of BARD1. The study demonstrates the usefulness of CGH-array in routine genetic analysis and, aside from the CHEK2 rearrangements, indicates there is a very low incidence of large rearrangements in BRCA1/2 and in the other eight candidate genes in families already explored for BRCA1/2 mutations. Finally, next-generation sequencing should bring new information about point mutations in intronic and flanking regions and also medium size rearrangements.

[Don't forget fallopian tubes! A morphologic and immunohistochemical study about Fallopian tubes with genetic risk (BRCA mutation)]. / N'oubliez pas les trompes ! Étude morphologique et immunohistochimique des trompes à risque génétique (mutation BRCA).

OBJECTIVES: The objective of this study was to describe morphologic and immunohistochemical features of precursor tubal lesions in prophylactically removed Fallopian tubes. PATIENTS AND METHODS: Hundred and forty-seven bilateral salpingectomies (genetic predisposition or group A: n=57; and control group or group B: n=90) were reviewed by two pathologists blinded to clinical data. Seven epithelial cytological and architectural features were studied to compare the degree of tubal epithelial abnormalities between the two groups. Immunohistochemical expression patterns of Ki67 and p53 were also evaluated. RESULTS: Serous tubal intraepithelial lesions (STIL) have been identified in group A with stronger expression for Ki67 and p53 (especially in BRCA 1 group) than in group B. DISCUSSION AND CONCLUSION: The current results show the importance of salpingo-oophrectomy in BRCA mutation carriers and the complete histopathological sampling of the Fallopian tubes.

[Ovarian carcinogenesis: recent and past hypotheses]. / La cancérogenèse ovarienne : théories actuelles et passées.

Ovarian carcinogenesis and the early stages of malignant transformation are limited because of the lack of a candidate precursor. There have been several proposed hypotheses: first, ovary and the ovarian surface epithelium and more recently observations have increasingly focused attention of the Fallopian tube. Moreover, molecular genetic analysis has designed two main pathways of tumorogenesis. In this review, we discuss the different and perhaps complementary hypotheses about ovarian carcinogenesis.

Comparison of dysplasia profiles in stimulated ovaries and in those with a genetic risk for ovarian cancer.

AIM: Ovarian epithelial dysplasia (OED) was first described after prophylactic oophorectomy for genetic risk of ovarian cancer. In light of Fathalla's incessant ovulation theory, this study was set up to describe the presence of ovarian abnormalities (dysplasia) after ovulation induction and to compare dysplasia profiles in stimulated and genetic risk ovaries. METHODS: One-hundred and twenty-four patients who had undergone salpingo-oophorectomies or ovarian cystectomies between 1990 and 2005 were reviewed. They were divided into three groups: (1) previous in vitro fertilisation (n=35); (2) prophylactic oophorectomies for genetic risk (n=27) and (3) fertile non-cancerous controls (n=62). Eleven cytological and architectural epithelial features were defined and a dysplasia score was calculated to quantify ovarian epithelial abnormalities. RESULTS: Mean dysplasia score was significantly higher in the genetic risk and stimulated ovary groups than in controls (9.55 versus 3.62, p<0.0001; 7.51 versus 3.62, p<0.0002, respectively). Cytological and architectural abnormalities were more frequent in the genetic risk group, while the profile of abnormalities was different in the genetic risk and stimulated groups. CONCLUSIONS: These findings support a possible relationship between OED and the use of ovulation-stimulating drugs. The increased dysplasia score in stimulated and genetic risk ovaries might be consistent with progression towards neoplastic transformation, and may justify the use of the term dysplasia or intraepithelial ovarian neoplasia. The observation of dysplasia in the stimulated group may differentiate women at risk. Conversely, the fact that the dysplasia profile after stimulation differs from that in genetic risk ovaries suggests that ovarian stimulation may predispose to a different evolution.

Report of a family segregating mutations in both the APC and MSH2 genes: juvenile onset of colorectal cancer in a double heterozygote.

BACKGROUND AND AIMS: Mutations in DNA mismatch repair genes are associated with high risk of digestive malignancies [hereditary non-polyposis colorectal cancer (HNPCC); Lynch syndrome]; mutations of APC and MYH are associated with classic and attenuated familial adenomatous polyposis (FAP). Although the early onset of tumors in both syndromes is characteristic of their genetic origin, pediatric malignancies remain rare. Certain reports have found familial colorectal cancer (CRC) occurring in very young patients associated with mutations in more than one gene. MATERIALS AND METHOD: A family corresponding to the Amsterdam criteria for HNPCC, including two cases of colorectal cancer before the age of 25 years, was analyzed for mutations in the MSH2 genes by sequencing. Because polyposis was observed in a patient who developed CRC at age 16, the APC gene was also sequenced. RESULTS: A truncating mutation in the MSH2 gene, c.258_259delTG, was carried by patients developing cancer of the colon (two patients), uterus, kidney, bladder, and/or small intestine at ages 16, 24, 43, 44, 45, and 57, respectively. A patient with CRC at age 16 was found to carry the APC c.3183_3187del5 mutation as well as the MSH2 mutation, and it is inferred that her father, deceased of CRC at age 24, was also a double heterozygote. INTERPRETATION: These results confirm that vigilance is required when interpreting molecular results for families with very young patients, as more than one gene may contribute to the genetic risk. Cancer screening measures must also be adapted to the earlier and more penetrant risk to double heterozygotes.

Complete mutation screening and haplotype characterization of BRCA1 gene in Tunisian patients with familial breast cancer.

Breast cancer, the most commonly diagnosed cancer in women, is the second leading cause of cancer death in women worldwide. To investigate the contribution of BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of all BRCA1 exons. We identified four different BRCA1 frameshift mutations: c.4041delAG, c.2551delG and c.5266dupC already been described and one novel mutation, c.211dupA, observed in two unrelated families. C.5266dupC has previously been found among Jewish Ashkenazi and Eastern European populations. Our study describes it in Arabic/Berber population. Five out of thirty two familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study is the first molecular investigation on the role of BRCA1 in hereditary breast cancer in North Tunisia.

Comparative clinical and transcriptomal profiles of breast cancer between French and South Mediterranean patients show minor but significative biological differences.

BACKGROUND: In Western countries, breast cancer incidence and mortality are higher than in Mediterranean countries. These differences have been ascribed to environmental factors but also to late-stage diagnostic and biological specific characteristics. PATIENTS AND METHODS: Between September 2002 and September 2005, we collected clinical data by phone counselling 180 French and Mediterranean breast cancer patients and performed microarray experiments. RESULTS: Characteristics of breast cancer in patients from Lebanon, Tunisia and Morocco were more aggressive (more SBR grade III and positive node invasion) and patients were 10 years younger at diagnosis. Sixteen differentially expressed genes such as MMP9, VEGF, PHB1, BRCA1, TFAP2C, GJA1 and TFF1 were also found. Additionally, an up-regulation of cytokeratins KRT8 and KRT18 may indicate a luminal B subtype in "South" (Lebanon, Tunisia and Morocco) tumors while "North" (France) tumors may more frequently be luminal A type. CONCLUSION: This study allowed the identification of specific clinical and transcriptomic parameters in patients from South Mediterranean countries.

Immunolocalization of BRCA1 protein in tumor breast tissue: prescreening of BRCA1 mutation in Tunisian patients with hereditary breast cancer?

BRCA1 is a tumor suppressor gene which is inactivated by mutation in familial breast and ovarian cancers. Over 300 different disease causing germ-line mutations have been described; 60% are unique to an individual family. This diversity and the large size of the gene lead us to search for a prescreening method for BRCA1 mutations. Since BRCA1 is a nuclear protein in normal cells, but reported by some authors to be cytoplasmic in breast tumor cells of patients with BRCA1 mutation, we evaluated immunohistochemistry as a prescreening technique to identify BRCA1 mutations in patients with familial presentation of breast cancer. Using a monoclonal antibody against the carboxy-terminal region of BRCA1, we performed immunohistochemistry on 18 tumor samples from patients with hereditary breast cancer. Cytoplasmic staining of BRCA1 was observed in 10 cases. Of the 18 tumors, 12 (66%) showed either BRCA mutation or BRCA1 accumulation or both, indicating that BRCA1 function might be lost in breast tumor cells not only through mutation, but also via abnormal cytoplasmic location. The immunohistochemical test used in this study would not be efficient as a pre-screening method of deleterious mutations, but it appeared useful to investigate tumor physiology.

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia.

Hereditary breast cancer accounts for 3-8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations--c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.

[To test the impact of hypnotherapy upon immunity and circadian rhythms among palliative cancer patients: a promising goal?]. / Tester l'impact de l'hypnothérapie sur l'immunité et les rythmes biologiques chez des patients cancéreux traités en palliatif: une cible prometteuse?

Epidemiological and clinical researches in the borderline domain between psychology and cancer have produced consequent results, despite the large variety of employed approaches and aimed goals: these results permit to define domains where new investigations still appear promising. If randomized prospective controlled trials that test the impact of psychosocial interventions, constitute to our mind a strategy that must not be bypassed, a special attention should be focussed on the following topics: 1) it seems necessary to add to standard goals (survival and quality of life) the evaluation of the impact on immunity and main biological rhythms (circadian and ultradian). Specific questionnaires should be included (pain, sleep, mood, self-esteem, life events...) and others may need to be developed or adapted (sexuality, spirituality, coping with death); 2) among types of psychosocial management, hypnosis and/or learning of self-hypnosis appears to be a modality of choice since some results have already been obtained on immune pathologies and also on cancer. Mixed to an approach of clinical psychology, such a management could arouse behavior changes toward pathology but also promote an improvement of biological rhythms (action on sleep...) and perhaps, by the way, an immune rebound; 3) on a methodological point of view, trials cannot be double-blind. The effort must then concern sample sizes, that were often insufficient in many trials, but also targeted populations: palliative cancer patients with a good performance status seem more relevant for this type of investigation, since psychosocial interventions usually improve quality of life.

Quantitative analysis of BRCA1, BRCA2 and Hmsh2 mRNA expression in colorectal Lieberkühnien adenocarcinomas and matched normal mucosa: relationship with cellular proliferation.

The human DNA mismatch repair gene hMSH2 is involved in the development of sporadic and hereditary nonpolyposis colorectal cancer. An increased risk of colorectal cancer has also been suggested in BRCA1 and BRCA2 mutation carriers. To address the relationship between the expression level of these genes and colorectal tumorigenesis, we studied BRCA1, BRCA2 and hMSH2 mRNA expression by real-time quantitative RT-PCR in 72 colorectal Lieberkühnien adenocarcinomas and matched normal mucosa. We investigated the relationship between mRNA levels and various clinicopathological parameters. The mean expression of BRCA1 3' and BRCA2 3' (mRNA pool), BRCA1 ex11 (with exon 11), BRCA2 ex12 (with exon 12) and hMSH2 mRNAs were increased in tumor samples. BRCA1 and BRCA2 mRNAs expressions were altered according to colon tumor site: BRCA1 3' and BRCA2 3' mRNAs levels were highest, respectively, in the right colon and left colon. No difference in hMSH2 mRNA levels was detected in relation to clinicopathological parameters. The mean SPF value was significantly higher in tumor than in non-tumor colonic tissue, and a high SPF value was correlated with high BRCA2 mRNA levels. BRCA2 3' mRNA levels tended to decrease as the Dukes' stage increased. In conclusion, the mechanisms of colorectal carcinogenesis seem to differ according to the right or left position of the tumor.

Quantification by affinity perfusion chromatography of phosphorylated BRCAl and BRCA2 proteins from tumor cells after lycopene treatment.

A new procedure for the quantification of phosphorylated BRCA1 (P-BRCA1) and BRCA2 (P-BRCA2) proteins in breast cell lines after different treatments was carried out. Cells were cultivated with [35S]-methionine and extracts subjected to three perfusion chromatographies. First heparin affinity chromatography purified cellular DNA-binding proteins. Subsequent specific immunoprecipitation of BRCA1 and BRCA2 proteins was performed with antibodies raised against BRCA1 or BRCA2. The immune complexes were isolated by protein A affinity chromatography. Phosphorylated BRCA1 or BRCA2 proteins were then purified with a Poros 20 AL column where anti-phosphothreonine and anti-phosphoserine antibodies were previously bound. The percentage of phosphorylated BRCA1 or BRCA2 proteins was calculated as follows: 100 x dpm of P-BRCA1 or P-BRCA2 eluted from the POROS 20AL column/total dpm eluted from POROS 20AL column. Treatment with 10 microM lycopene increased P-BRCA1 and P-BRCA2 in the breast tumor cell line MCF7 but not in MDA-MB-231 or MCF-10a, breast tumor or fibrocystic cell lines, respectively.

The effects of lycopene on the proliferation of human breast cells and BRCA1 and BRCA2 gene expression.

The purpose of this study was to demonstrate the effects of lycopene, the major tomato carotenoid, on the expression of the BRCA1 and BRCA2 genes in three breast tumour cell lines, MCF-7, HBL-100, MDA-MB-231 and the fibrocystic breast cell line MCF-10a. Flow cytometry analysis showed a G(1)/S phase cell cycle-arrest after treatment of the cells with 10 microM lycopene for 48 h. mRNA expression was studied by quantitative reverse transcription-polymerase chain reaction using the Taqman method. We observed an increase of BRCA1 and BRCA2 mRNA in the oestrogen receptor (ER)-positive cell lines (MCF-7 and HBL-100), and a decrease (MDA-MB-231) or no change (MCF-10a) in the ER-negative cell lines. BRCA1 and BRCA2 proteins were quantified by perfusion affinity chromatography. No variation in their expression was observed. These preliminary results on the effects of lycopene on the expression of BRCA1 and BRCA2 oncosuppressor genes in breast cancer may reflect cross-talk between the oestrogen and retinoic acid receptor (RAR) pathways.

In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases.

There is a growing body of evidence to support the efficacy of topical imiquimod in the treatment of primary skin carcinomas. Conflicting data exist concerning the use of imiquimod for the treatment of skin melanoma metastases. To date, only the impact of imiquimod on cytokines involved in immunological processes has been studied extensively. We report a woman successfully treated with imiquimod (once daily for 8 weeks) for skin melanoma metastases in whom we investigated the expression of molecules involved in metastasis and angiogenesis. Before and after treatment, a skin lesion was biopsied and the expression of the following molecules was investigated using real-time reverse transcription-polymerase chain reaction: matrix metalloproteinase (MMP)-1, 2 and 9 and their inhibitors KiSS-1 and tissue inhibitor of metalloproteinase (TIMP)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor-2, and angiogenesis inhibitors (thrombospondin-1 and 2). Interferon (IFN)-alpha was also investigated as an in vivo marker of imiquimod activity. IFN-alpha was upregulated by the treatment. Under imiquimod, the following molecules were upregulated: TIMP-1, KiSS-1 and MMP-1. MMP-2 expression was not modified. MMP-9 expression was dramatically decreased. The expression of angiogenesis inhibitors was slightly increased but VEGF expression remained at a basal level. These results suggest that imiquimod could downregulate metastasis invasion and angiogenesis. However, these data were obtained at a transcriptional level and from a single case, and further investigations should include migration assays and additional cases in order to confirm that imiquimod may be safely used for treatment of melanoma metastases.

Interaction between GSTM1-null and CYP2D6-deficient alleles in the pathogenesis of Parkinson's disease.

The present study was conducted to examine the interaction between cytochrome p450 2D6: CYP2D6 (phase I) poor metabolizer (PM) and glutathione S-transferase M1: GSTM1 (phase II) null genotypes, among 103 unrelated French Parkinson's disease (PD) patients. Both genes are involved in the biotransformation process, and the main objective of that work is to assess synergic effect between CYP2D6 PM and GSTM1 null genotypes in PD patients. Patients with both GSTM1 null genotype and poor metabolizer CYP2D6 have shown a strong dependency of multiplicative interaction (9.50; P = 0.016); this have also been observed when combining GSTM1 null with CYP2D6*4 deficient alleles, but were at the limit of significance (2.18; P = 0.076). Such a combination of polymorphic peculiarities in studied metabolic genes might represent additional risk factor for development of sporadic PD.

Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines.

The phytochemical resveratrol, found in grapes, berries and peanuts, has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumour initiation, promotion and progression. Resveratrol is also a phyto-oestrogen, binds to and activates oestrogen receptors that regulate the transcription of oestrogen-responsive target genes such as the breast cancer susceptibility genes BRCA1 and BRCA2. We investigated the effects of resveratrol on BRCA1 and BRCA2 expression in human breast cancer cell lines (MCF7, HBL 100 and MDA-MB 231) using quantitative real-time RT-PCR, and by perfusion chromatography of the proteins. All cell lines were treated with 30 microM resveratrol. The expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found. These data indicate that resveratrol at 30 micro M can increase expression of genes involved in the aggressiveness of human breast tumour cell lines.