The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer.

Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. MATERIALS AND METHODS: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. RESULTS: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. CONCLUSION: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.

Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.

PURPOSE: Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated. METHODS: In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed. RESULTS: Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage. CONCLUSIONS: Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.

Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial.

BACKGROUND: The management of hormonal deficiency symptoms in breast cancer survivors is an unsolved problem. While hormone replacement therapy (HRT) may increase the risk of breast cancer in healthy women, its effects on recurrence is unclear. Observational studies have suggested decreased recurrence rates from HRT. The few clinical trials in this field have all been closed preterm. METHODS: The Stockholm trial was started in 1997 and designed to minimise the dose of progestogen in the HRT arm. Disease-free women with a history of breast cancer were randomised to HRT (n=188) or no HRT (n=190). The trial was stopped in 2003 when another Swedish study (HABITS, the Hormonal Replacement After Breast Cancer - Is it Safe?) reported increased recurrence. However the Stockholm material showed no excess risk after 4 years of follow-up. A long term follow-up has now been performed. FINDINGS: After 10.8 years of follow-up, there was no difference in new breast cancer events: 60 in the HRT group versus 48 among controls (hazard ratio (HR)=1.3; 95% confidence interval (CI)=0.9-1.9). Among women on HRT, 11 had local recurrence and 12 distant metastases versus 15 and 12 for the controls. There were 14 contra-lateral breast cancers in the HRT group and four in the control group (HR=3.6; 95% CI=1.2-10.9; p=0.013). No differences in mortality or new primary malignancies were found. INTERPRETATION: The number of new events did not differ significantly between groups, in contrast to previous reports. The increased recurrence in HABITS has been attributed to higher progestogen exposure. As both trials were prematurely closed, data do not allow firm conclusions. Both studies found no increased mortality from breast cancer or other causes from HRT. Current guidelines typically consider HRT contraindicated in breast cancer survivors. Findings suggest that, in some women symptom relief may outweigh the potential risks of HRT.

The in vitro toxicology of Swedish snus.

Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes.

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer.

Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 × 2 factorial study design to goserelin, tamoxifen, the combination of goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the end point first event. In this Stockholm sub-study, at a median follow-up of 12.3 years, goserelin reduced the risk of first event by 32% (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27% (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (P = 0.021) compared with no endocrine treatment. In highly ER-positive tumours, there were 29% fewer events among goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER-positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.

Work status and life changes in the first year after breast cancer diagnosis.

OBJECTIVE: The aims of this study were to generate new knowledge about factors predicting return to work (RTW) among women treated for early-stage breast cancer, and about changes in life satisfaction, and coping, and to examine the association between these concepts and RTW. METHODS AND PARTICIPANTS: A cohort of 102 women aged 18-64 were assessed six weeks, six months, and ten months after surgery using data from questionnaires and medical files. RESULTS: Factors independently predicting no RTW at six months were: chemotherapy, > 30 days of sick leave during the previous 12 months, low satisfaction with activities of daily living, and not having been born in Sweden. No RTW at ten months was predicted by irradiation to breast/chest wall and regional nodes, and low satisfaction with vocational situation. Global life satisfaction was higher among the working women, both six months after surgery and ten months after surgery. The working women used more positive coping resources as compared to the sick-listed women, particularly sick-listed women treated with chemotherapy. CONCLUSION: Factors associated with RTW appear to include not only treatment-related factors such as chemotherapy and irradiation, but also psychosocial factors such as life satisfaction and coping resources. With increased understanding of the complex factors related to RTW after a breast cancer diagnosis, it will be possible to identify and support survivors who are at risk of being marginalized from the labor market.

The impact of RNA standardization and heterogeneous gene expression on the results of cDNA array of human breast carcinoma.

cDNA microarray is an established technique. However, difficulties such as handling tissue samples under RNase-free conditions, the heterogeneous tumor composition, i.e. non-malignant versus malignant cells and different pathologic types of malignant cells, and lack of appropriate reference may limit the potentially benefit of this method in clinical use. In this study, we examined how standardization of gene expression to total mg RNA or mg tissue and tumor heterogeneity affect the final results. We found that the gene expression of human breast tumors was approximately 9 times higher in malignant tissue as compared to the non-malignant tissue when expressed per total mg RNA, but approximately 40 times higher when expressed per mg tissue. Genes that were expected to act as housekeeping genes (PUC18, RPL and beta-actin) varied between different parts of the tumor and also between non-malignant and malignant tissues, excluding them as reference genes. We also found that the gene expression differed in various parts of the breast tumor, probably due to a mixture of different types of cells, i.e. non-malignant and malignant cells. To find out if the variations in the gene expression were due to cell heterogeneity we used microdissection to collect malignant cells separately. We found that the gene expression was markedly different in the isolated malignant cells as compared to the gene expression of the bulk tumor tissue. Thus, to be able to evaluate results from cDNA array gene expression experiments it is, to our opinion, necessary to work with pure tumor cell populations, until solid information is available on the impact of stromal component. Housekeeping genes should be handling with care and mg tissue may be preferred instead of microg RNA for standardization.

Cancer patients without a known primary: incidence and survival trends in Sweden 1960-2007.

BACKGROUND: Metastatic cancer from an unknown primary tumour (CUP) is a common and heterogeneous clinical entity. In Sweden like in many other countries, the continuum of care for such patients remains to be established. MATERIAL AND METHODS: Data on CUP cases reported to the Swedish Cancer Registry during 1960 through 2007 was used to assess time trends for incidence, survival, and histological tumour type. RESULTS: There was an upward trend for the age-adjusted incidence until the late 1990s. This roughly paralleled the increase for all reported cancers during the same period. The increase of CUP mainly concerned patients aged above 50 years, and tumours classified as adenocarcinomas. The relative survival at 12 months after a diagnosis of CUP was estimated at 20%. However, after 12 months the relative survival levelled of and the 5-year estimate was 10-15% which suggests that a small proportion of CUP cases may be cured. Relative survival was highly dependent on age with substantially better outcome for young patients, particularly those aged below 30 years. We observed no time trend for survival. DISCUSSION: Cases diagnosed as CUP includes patients with metastatic spread from a wide variety of tumours although certain tumour types probably are overrepresented, for example, cancers in sites that are difficult to examine clinically. Incidence trends probably represent the sum of trends for these cancers as well as diagnostic trends. The decreased incidence observed during the last decade might thus be explained in terms of a combination of improved diagnostic methods to detect primary tumours and decreasing incidence for e.g. pancreatic cancer and lung cancer among males. There is a need of evidence-based programs that define the continuum of care for CUP patients. Such a program is currently being developed through collaboration between all health care regions in Sweden.

Predictors of return to work ten months after primary breast cancer surgery.

BACKGROUND: The most common female cancer in Western countries is breast cancer and women diagnosed with this disease are often under 65 years old. With increasing prevalence of survivors it is important to shed light on problems facing these women after diagnosis and treatment. The aim of this study was to assess factors predicting return to work (RTW) in women with early-stage breast cancer. MATERIAL AND METHODS: A cohort of 102 women aged 18-64 with early-stage breast cancer who had undergone curative primary surgery with or without systemic adjuvant therapy were followed for 10 months using data from questionnaires and medical files. RESULTS: Ten months after primary surgery, 59% of the women had returned to work while 41% were sick-listed part-time or full-time. After adjusting for age, health status, life satisfaction, vocational situation, and irradiation to the breast/chest wall and regional nodes, a multivariate logistic regression revealed the following factors as being negatively associated with RTW: a high-demand job (OR=0.1, 95% CI 0.0-0.8), axillary node dissection (OR=0.1, 95% CI 0.0-0.6), and treatment with chemotherapy (OR=0.1, 95% CI 0.0-0.7). DISCUSSION: Treatment factors and high demands at work play an important role in RTW for women with early-stage breast cancer.

Predicting distant dissemination in patients with early breast cancer.

BACKGROUND: Prediction of distant metastases is of paramount importance in the knowledge and management of breast cancer patients. The objective of this study was to assess conventional prognostic factors in a large database of patients with early breast cancer, including those with small tumors diagnosed through regional screening, to determine the risk of distant dissemination. METHODS: The study included 4,797 patients of the Stockholm database who did not receive systemic adjuvant treatments. The main endpoint was metastasis free-interval. Individual risks of distant metastasis were estimated using the regression coefficients of the significant prognostic factors in Cox multivariate analyses. For each level of metastatic risk the pattern of failure was analyzed by a model assuming competing risks. RESULTS: The three independent significant prognostic factors were histologic tumor size, number of involved axillary lymph nodes and progesterone receptor level. However, the latter factor added limited additional information of borderline clinical significance. Thus, subsequent estimations were done with a prognostic score taking into account only the former two most performant factors in the whole population. The risk of distant metastasis of observed values of tumor size categories fitted with published results of a series containing significantly larger tumors. A large variation of tumor size predicts 10-year distant metastasis risk ranging from below 10% up to 90%. Tumors of 10 mm or less had a 10-year metastatic risk of less than 10%. CONCLUSIONS: The results of this study are consistent with a linear effect of tumor size, within the range of data, on 10-year distant dissemination probabilities. Further refinement on prognostic value is needed for tumors of 15 mm or less.

Long-term pattern of disease recurrence among patients with early-stage breast cancer according to estrogen receptor status and use of adjuvant tamoxifen.

PURPOSE: Recent studies on the pattern of gene expression in estrogen receptor positive and negative tumours have revealed profound differences according to receptor status. However, it remains unclear if these differences reflect phenotypic traits in addition to sensitivity to endocrine therapy. This paper describes the long-term pattern of disease recurrence among ca. 2,600 pre- and post-menopausal patients with primary breast cancer according to estrogen receptor status. MATERIAL AND METHODS: The study was based on patients with an operable, invasive breast cancer entered in one of three controlled clinical trials conducted by the Stockholm Breast Cancer Group. We selected those 2,562 patients who had been randomly allocated between adjuvant tamoxifen and no adjuvant systemic therapy. These patients had a known estrogen receptor status. RESULT: Tamoxifen reduced locoregional (8.8% vs. 12.4%, hazard ratio (HR), 0.66; 95% CI, 0.52-0.83; P = 0.001, distant recurrences (17.2% vs. 20.2%, HR, 0.81; CI, 0.68-0.97; P = 0.018, as well as breast cancer death (18.7% vs. 23.7%, HR, 0.78; CI, 0.67-0.92; P = 0.002). Among patients not allocated to tamoxifen there was no significant differences in term of neither locoregional (12.4% vs. 12.4%, HR, 1; CI, 0.72-1.41; P = 0.98), nor distant metastases (18.5% vs. 20.7%, HR, 1.11;CI, 0.85-1.45; P = 0.46) according to ER status. The pattern of metastases was not different in ER positive comparison with ER negative. CONCLUSION: The results showed that the mentioned substantial differences in terms of gene expression appeared mainly to be related to endocrine sensitivity and not to metastatic potential. However, a slight advantage during the first five years for the ER positive versus ER negative patients in terms of cumulative incidence of events, suggested that ER negativity in some cases is correlated with an increased tumour growth rate.

p53 polymorphic variants at codon 72 and the outcome of therapy in randomized breast cancer patients.

BACKGROUND: Adjuvant therapy of breast cancer patients reduces the risk of recurrence and mortality, although, a substantial proportion of patients acquire resistance and relapse in the disease. Predictors of therapeutic response are therefore important to avoid both therapy resistance and the side effects of inefficient regimes. The p53 protein is a key determinant to induce either growth arrest or apoptosis in response to cytotoxic stress. METHODS: In the search for predictive markers of cancer therapy we investigated a common Arg72/Pro72 polymorphism in the p53 gene, which has been shown to influence the apoptotic potential. Using PCR and RFLP we genotyped 220 breast cancer patients randomized to radiotherapy versus chemotherapy and tamoxifen versus no tamoxifen. RESULTS: Oestrogen-receptor positive patients possessing at least one Pro72 allele had better distant recurrence-free survival when randomized to tamoxifen compared to those who were not (P=0.0033), as also demonstrated by the significantly decreased hazard ratio (HR=0.28, 95% CI 0.12-0.65). Among patients homozygous for the Arg72 genotype the outcome was approximately equal between tamoxifen treated and non-tamoxifen treated patients (P=0.65). When the calculated hazard ratios for the genotypes were compared by an interaction test a significant difference was found (P=0.0088). CONCLUSION: The present report indicates that the codon 72 polymorphism in the p53 gene may be a predictor of tamoxifen response, suggesting that breast cancer patients lacking the Pro72 allele might be candidates for other therapies.

Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer.

BACKGROUND: The prognostic value of the concentration of serum thymidine kinase 1 (S-TK1) with regard to recurrence in low risk breast cancer patients, 3 months after surgery was evaluated. PATIENTS AND METHODS: The concentration of S-TK1 in serum was determined in 120 breast cancer patients at the time of surgery and in 67 patients 3 months after surgery, by anti-TK1 chicken IgY antibody, using a dot-blot immuno-assay. The S-TK1 concentration was compared with the serological activity of thymidine kinase (STK) and of carbohydrate antigen (CA 15-3). RESULTS: A statistically significant trend (unadjusted) was found for recurrence (distant or loco-regional) in patients with a higher S-TK1 concentration, as compared with patients with a lower S-TK1 concentration. A multivariate analysis gave the same results. The hazard rate ratio for developing distant and/or loco-regional recurrence in patients with a higher S-TK1 concentration was about six to seven times higher than in patients with a lower S-TK1 concentration. CONCLUSION: Our results indicate that the S-TK1 concentration is higher in patients developing distant and/or loco-regional recurrence 3 months post-surgery.

Time-dependent RNA degradation affecting cDNA array quality in spontaneous canine tumours sampled using standard surgical procedures.

Heterogeneous gene expression in tumours and the degradation of RNA when sampling under non-RNAse-free conditions may limit the potential benefit of cDNA array studies. This study examines changes in the integrity of RNA by means of RNA gel electrophoresis at various post-operative intervals on canine mammary tumours (n=10) and malignant lymphoma (n=1). The tumours were cut into pieces (3-5 mm diameter, approximately 50 mg) and kept in tubes without RNAse-free buffer at room temperature. No special precautions were taken to avoid the influences of Rnase; rather, normal surgical procedures were used. We found that total RNA of the mammary tumours started to degrade within 30 min of the operation, and the rate of degradation increased up to 4 h, which was the last time point included in this study. RNA in the lymphoma tumours degraded more rapidly, and was completely degraded at 30 min post-operation. The degradation of mRNA in the mammary tumours, as studied by human cDNA arrays, was heterogeneous, i.e. some mRNA degraded completely, some only partially. This indicates that the mRNA degradation rate varied depending on the type of mRNA. However, since we found that gene expression differs depending on the part of the mammary tumour examined, one cannot exclude that the variation in the mRNA degradation rate may simply reflect heterogeneous gene expression within the tumour. We conclude that RNA integrity is unaffected immediately after sampling under non-RNAse-free conditions; however, the tumour sample should be preserved under RNAse-free conditions within 15 min to avoid RNA degradation. This is a much shorter time interval than previously reported in other similar studies; however, these studies generally treated normal tissue, under which 3-5 h non-RNAse-free conditions have been found not to affect RNA quality.

Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial.

From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94; P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed.

Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients.

BACKGROUND: Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. METHODS: The patients were genotyped using PCR followed by cleavage with restriction enzymes. RESULTS: Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11-0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21-1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19-0.74, P = 0.0041). CONCLUSION: The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort.

Aromatase inhibitors in the treatment of early and advanced breast cancer.

The third generation aromatase inhibitors anastrozole, exemestane, and letrozole have been compared with tamoxifen and other endocrine therapies in several studies in early and advanced breast cancer. These studies are reviewed in this report. Based on the available evidence, the panel recommends that adjuvant treatment with tamoxifen for 5 years should no longer be considered as the sole standard but that a third-generation aromatase inhibitor should be used either alone or in a sequence with tamoxifen in the adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer. Third generation aromatase inhibitors may be considered as the first line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women, and they may also be used for preoperative therapy of breast cancer.

Genes related to growth regulation, DNA repair and apoptosis in an oestrogen receptor-negative (MDA-231) versus an oestrogen receptor-positive (MCF-7) breast tumour cell line.

The molecular mechanism(s) behind the development of endocrine resistance in breast cancer remains controversial. Here, we compare the capability of oestrogen receptor (ER)-negative cells (MDA-231) versus ER-positive tamoxifen-sensitive cells (MCF-7) to handle DNA repair, transmit signals from damaged DNA, initiate cell death via apoptosis, and then to control transmitted signals from the cell cycle and to synthesize growth factors and receptors. Genes related to these events were studied by cDNA micro-array. Normal human breast cells (H2F) and human lymphoblastoid tumour cells (CEM) were used as controls. Of the 18 genes investigated, 10 genes showed differences in their expression between the cell types. The ER-negative cells showed higher expressions of BRCA1, BRCA2, cdc2, cyclin B1, cyclin D1, cyclin E, IGFBP-3, TGF-alpha, TGF beta 2 and a lower expression of TGF beta R1. No differences in the expressions of bax, bcl-2, p53, p21 and GADD45 were found between the two cell lines. We found that the ER-negative cells were characterized by: (1) a stimulated expression of growth factors and cell cycle regulation compounds, (2) improved DNA repair capacity, but (3) no change in DNA damage signals and apoptotic pathways. Improved DNA repair capacity of ER-negative cells would have a growth advantage over ER-positive tumours when receiving antitumour therapy.