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Lars Erik Rutqvist

Lars Erik Rutqvist
Anatello AB · Scientific Affairs

M.D., Ph. D

About

300
Publications
25,002
Reads
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27,059
Citations
Additional affiliations
September 2013 - present
Vinča Institute of Nuclear Sciences
Position
  • Professor
September 2000 - September 2005
Karolinska University Hospital at Huddinge
Position
  • Head of Department

Publications

Publications (300)
Article
Background and Objective The present study was undertaken to ascertain whether the modulatory effects of blueberries on cell proliferation induced by Swedish snus in the rat forestomach epithelium is mediated via abrogation of the PI3K/Akt/NFκB signalling axis that regulates cell fate decision. Methods The transcript and protein expression of gene...
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Full-text available
Long term exposure to oral smokeless tobacco may induce lesions in the oral cavity characterized by a hyperplastic epithelium. The possible role of nicotine and the physical properties of oral tobacco for developing these lesions, as well as of dysplasia and neoplasia is unclear. Low nitrosamine Swedish snus as well as non-genotoxic butylated hydro...
Article
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 metho...
Article
Background: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if...
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Head and neck (H&N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analy...
Article
Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. Res...
Article
Long-term survival of H&N cancer patients has not improved significantly over the last 30 years. The possibility of using circulating blood cell phenotypes as a prognostic biomarker of H&N cancer patient was investigated in this study. Pre-treatment, circulating T lymphocyte subpopulations as well as the survival time of the patients in question we...
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The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin (‘Zoladex’) and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer.
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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 f...
Article
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Long-term survival of this patient group has been marginally improved during the last 30 years. This is due to the high recurrence rate of local primary or development of second primary tumours in the patients. We found that normal-appearing surgical margin...
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Introduction: The ability of Swedish snus to serve as a smoking cessation aid has been documented in several observational, population surveys from Scandinavia, but randomised clinical trials provide more reliable information on efficacy. Aims: To perform a systematic review and meta-analysis of randomised clinical trials of Swedish snus as an aid...
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Background Most smokers who quit typically do so unassisted although pharmaceutical products are increasingly used by those who want a quitting aid. Previous Scandinavian surveys indicated that many smokers stopped smoking by switching from cigarettes to smokeless tobacco in the form of snus. However, usage of various cessation aids may have change...
Article
Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and S...
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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 concentrat...
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Snus is a low-nitrosamine smokeless product that appears to be safer than other smokeless products. Evidence indicates that snus has been used as an effective smoking cessation aid in Scandinavia. No randomized controlled trial has directly tested the efficacy of snus for smoking cessation. This randomized, double-blind, placebo-controlled multicen...
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ABSTRACT: Epidemiological studies suggest that smokeless tobacco in the form of Swedish snus has been used by many smokers in Scandinavia to quit smoking, but the efficacy of snus has so far not been evaluated in controlled clinical trials. We conducted a randomized, double-blind, placebo-controlled, clinical trial aimed at assessing the efficacy o...
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Background: Ovarian ablation improves survival in premenopausal women with early breast cancer, but the potential added value by luteinizing hormone-releasing hormone agonists (LHRH-a) to tamoxifen, is still not clear. There has been lack of data reported separately for patients who underwent randomization to both LHRH-a and tamoxifen. Patients and...
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Some smokeless tobacco products, such as Swedish snus, are today considered to be associated with substantially fewer health hazards than cigarettes. This risk differential has contributed to the scientific debate about the possibilities of harm reduction within the tobacco area. Although current manufacturing methods for snus build on those that w...
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The adverse health effects of cigarette smoking are well established including the increased risk of various types of cancer. In this study, the direct effects of ethanol, pure nicotine, cigarette smoke extract and Swedish type smokeless tobacco (Snus) extract on normal cells were investigated. Primary normal adult human endothelial cells and fibro...
Article
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. A cohort of 102 women aged 18-64 were assessed six weeks, six months, and ten months...
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Long-term survival of head and neck squamous cell carcinoma (HNSCC) patients has not improved significantly during the last 20 years and recurrent disease is frequently observed. In this study, the potential presence of pre-malignant cells or rare malignant cells at the time of diagnosis in HNSCC was investigated. Fifty-nine biopsies obtained from...
Article
JOHNSSON A., FORNANDER T., RUTQVIST L.E. & OLSSON M. (2010) European Journal of Cancer Care19, 317–323 Factors influencing return to work: a narrative study of women treated for breast cancer The purpose of this qualitative study was to identify factors contributing to a successful return to the labour market after treatment for breast cancer from...
Article
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 clinic...
Article
The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1 347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter ≤ 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1136 patients (84%). At a...
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The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1 622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and deat...
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Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282 777 women (156 911 invited and 125 866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relat...
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Flow cytometry was performed on frozen specimens from the primary tumour of 184 women with recurrent breast cancer. No significant association was seen between DNA ploidy and the other prognostic factors investigated. Patients with a high S-phase fraction had more often a negative estrogen receptor (ER) status and a short disease-free interval. A s...
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This synthesis of the literature on radiotherapy for breast cancer is based on 97 scientific articles, including 5 meta-analyses, 38 randomized studies, and 27 retrospective studies. These studies involve 387 634 patients. Radiotherapy is the most effective method for preventing locoregional recurrence following primary surgery for invasive breast...
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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. Data on CUP cases reported to the Swedish Cancer Registry during 1960 through 2007 was used to assess time trends for incidence, survival, an...
Article
Few studies have described how patients receiving chemotherapy experience taste/smell changes (TSCs). Food and meal situations have important meaning beyond nutrition, so these common symptoms may affect daily lives. This study aims to investigate distress and impact on daily life from TSCs in patients receiving cancer chemotherapy, analyze reporte...
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Both adjuvant therapy and mammography screening can decrease breast cancer mortality and there is a need of knowing to what extent those two modalities are used in the population. Screening coverage is well documented but there is a scarcity of population-based data on use of systemic adjuvant treatment. To describe the introduction, and trends in...
Article
Taste and smell changes (TSCs) are known side effects of chemotherapy, but smell changes (SCs) in the absence of taste changes are understudied. This study aims to explore SCs occurring without taste changes during chemotherapy, to better understand the characteristics of such changes, and how these experiences affect patients in their daily lives....
Article
Few studies have described how patients receiving chemotherapy experience taste/smell changes (TSCs). Food and meal situations have important meaning beyond nutrition, so these common symptoms may affect daily lives. This study aims to investigate distress and impact on daily life from TSCs in patients receiving cancer chemotherapy, analyze reporte...
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Full-text available
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 wom...
Article
Many cancer patients continue to smoke past diagnosis and treatment, even though smoking in some cases may cause more side effects and increase the risk of treatment failure. We developed and evaluated a nurse-led smoking cessation programme on 50 patients with head and neck (H&N) cancer undergoing radiotherapy (RT) with 1-year follow-up. To evalua...
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This study explores the prevalence of self-reported taste and smell changes (TSCs) during chemotherapy and relationships between TSCs and demographic and clinical factors. Consecutive patients who had received chemotherapy for > or =6 weeks at 11 outpatient chemotherapy units completed a questionnaire developed for this survey. Seventy-five percent...
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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 di...
Article
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 recurre...
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Few studies explore patients' experiences of smell and taste changes during cytotoxic chemotherapy. Issues, such as how such changes impact daily life, their consequences, and how patients respond to chemotherapy-induced chemosensory changes, have not previously been systematically addressed. The aim of this study was to examine these questions by...
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Full-text available
The phosphatidylinositol 3'-kinase/Akt pathway is frequently altered in breast cancer. PTEN, a phosphatase that opposes the effect of phosphatidylinositol 3'-kinase, can be mutated or lost, whereas the PIK3CA gene is mutated. These have been proposed as alternative mechanisms, and their clinicalpathology significance is under discussion. In this st...
Article
To investigate the expression and predictive role of the Mre11/Rad50/Nbs1 (MRN) complex and the ataxia-telangiectasia mutated protein (ATM) for the outcome of radiotherapy in breast cancer patients. The protein expression of ATM and the DNA repair proteins in the MRN complex were investigated using immunohistochemistry in tumors from 224 women with...
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Relatively few studies have addressed problems regarding return to work after primary treatment for early-stage breast cancer. The purpose of this study was to investigate whether socio-economic and treatment-related factors were associated with problems of returning to work among pre-menopausal women included in a randomized trial of adjuvant endo...
Article
The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. A total of 2,738 postmenopausal women with invasive, early stage disease were randomised between tamoxifen for 2 or 5 years, or no adjuvant endocrine therapy. Among high-risk patients the treatment was given aga...
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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. 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 a...
Article
A program to ensure an equivalent standard of care for all patients with breast cancer was initiated in the Stockholm area in the mid 1970s. As part of an evaluation of this program, social gradients in clinical stage at presentation and survival were analyzed among patients diagnosed during 1977 through 1997. The patients (n = 15,021) were selecte...
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COX-2 is upregulated in many breast tumors, and one of the products of COX-2 is PGE2 that is suggested to upregulate aromatase through cAMP signaling in breast cancer. Although aromatase can increase the estrogen levels in tumors, 17beta-hydroxysteroid dehydrogenase (17HSD) activity is finally needed for the estrone/estradiol regulation. The aim of...
Article
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 deter...
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Full-text available
P21WAF1/Cip1 (p21) translocates to the cytoplasm inducing cell cycle progression and survival upon Akt/PKB activation. We studied whether heregulin beta1 (HRGbeta1), that activates the PI3K/Akt and MAPK pathways, also misallocates p21. We also explored whether HRGbeta1 interferes with the effects of tamoxifen. The clinical material studied helped u...
Article
The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin ('Zoladex') and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was...
Article
Full-text available
For many years, loco-regional radiotherapy was the standard postoperative treatment for node positive breast cancer patients in Sweden. Because of encouraging results from trials of adjuvant chemotherapy in the mid 1970s, the Stockholm Breast Cancer Study Group decided to directly compare postoperative radiation (RT) with adjuvant CMF-type chemothe...
Article
The aim of the present study was to define the proportion of different levels of family history in a cohort of consecutive breast cancer patients from the Stockholm region, and to assess whether familial breast cancer has phenotypic traits different from those of sporadic patients. All incident breast cancer patients in a 19-month period were eligi...
Article
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 (...
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Full-text available
Background in early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods...
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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 patien...
Article
Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy...
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Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomise...
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In 1997 two independent randomized clinical trials, Hormonal Replacement Therapy After Breast Cancer--Is It Safe? (HABITS; 434 patients) and the Stockholm trial (378 patients), were initiated in Sweden to compare menopausal hormone therapy with no menopausal hormone therapy after diagnosis of early-stage breast cancer. Much of the design of both st...
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The cDNA array technique is an efficient approach for studying the expression of a large number of genes in a single experiment. The cDNA array analysis indicates the relative level of corresponding gene expression from a specimen and a reference. Our investigation was performed to address the significance of reference RNA on the outcome of the can...
Article
For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in...
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Full-text available
Several recent epidemiologic studies on occupational magnetic field exposure have suggested an association with female breast cancer. The purpose of this study was to test this hypothesis by using the extensive Swedish population registers in combination with improved exposure assessment. The study base consisted of all women between 1976 and 1999...
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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 genet...
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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 s...
Article
Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatment of rectal cancer that have emerged in the past 20 years. The aim of this study was to evaluate the effects of an initiative to teach the TME technique on outcomes at 5 years after surgery. TME-based surgery was introduced in Stockholm in 1994. The s...
Article
Radiation therapy for head-and-neck cancer requires a reliable immobilization for an accurate and consistent treatment setup. This prospective, randomized study was done to compare two types of Posicast thermoplastic face masks, in terms of reproducibility, patient comfort, tolerability, and skin damage. The patients were randomly assigned to use a...
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Full-text available
To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone (LHRH) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer. We recruited 89 women from two centers in Stockholm participating in a randomized multicenter trial of three different endocrine...
Article
To reduce the risk of seroma after modified radical mastectomy in breast cancer patients, the use of suction axillary drainage is a standard procedure. The optimal time to remove the drain is not established. Whether the removal or preservation of the pectoral fascia influences the risk of seroma formation or loco-regional recurrence rate remains u...
Article
Information on whether surgery has been 'curative' is essential for prediction of prognosis and for selection of patients for adjuvant treatment. The aim of this study was to analyse the prognostic value of surgeons' and pathologists' assessments of tumour clearance in patients with primary rectal cancer who underwent resection. A total of 1550 pat...
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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 the...
Article
Endocrine therapy remains a cornerstone of systemic therapy for breast cancer even though it was first introduced more than a century ago. In the past three decades a large number of randomized trials involving several tens of thousands of patients have been performed to determine the role of endocrine therapy in the adjuvant setting. The results o...
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To compare the effects of tamoxifen and megestrol acetate on liver proteins, androgens, and glucocorticoids during adjuvant treatment for postmenopausal breast cancer. A subgroup of women within a large prospective multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women were randomized to receive either continuous tamoxife...