Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007124 (ductal carcinoma in situ)
 3,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen was the first in a class of drugs now commonly referred to as selective estrogen receptor modulators or SERMs. SERMs exhibit tissue-specific estrogenic agonist/antagonist activity through their ability to bind to the estrogen receptor alpha (ER) protein and interact with coregulatory proteins, thereby modulating transcription of estrogen target genes. Since its first approval by the United States Food and Drug Administration (FDA) in 1977, tamoxifen has been found to (a) lower the risk of recurrence and death for women with early-stage hormone receptor-positive breast cancer, irrespective of menopausal and node status or use of adjuvant chemotherapy; (b) reduce the risk of invasive breast cancer following breast conservation in women with ductal carcinoma in situ (DCIS); and (c) reduce the risk of breast cancer in high-risk women. Toremifene is the only other SERM approved by the FDA for breast cancer treatment. However, it offers no clear clinical advantage over tamoxifen in the adjuvant or metastatic settings. Several other SERMs are in various phases of clinical development. In addition, strategies to combine SERMs with other endocrine therapy like ovarian suppression or aromatase inhibitors are active areas of investigations. At present, SERMs are recognized as the first targeted and relatively nontoxic medical therapy for women with high-risk or steroid hormone receptor-positive breast cancer.
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PMID:Use of SERMs for the adjuvant therapy of early-stage breast cancer. 1179 84

Chemoprevention for breast cancer is both old and new. It has long been appreciated that early ovarian ablation dramatically reduces the incidence of breast cancer in premenopausal women. It was subsequently demonstrated, in the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview, that tamoxifen results in a 40% or greater reduction in the incidence of contralateral breast cancer. Now, the National Surgical Adjuvant Breast and Bowel Project (NSABP) has shown a similar reduction in a randomized trial [Breast Cancer Prevention Trial (BCPT)] comparing tamoxifen and placebo in women aged 35 years or over at increased risk of developing breast cancer because of age, family history, or other factors. In this trial, the incidences of both ductal carcinoma in situ (DCIS) and invasive cancer were reduced. Reduction in incidence was similar over all years of the study and in all subgroups of high-risk women. However, all of the reduction was confined to estrogen receptor (ER)-positive tumors. Raloxifene, a newer selective estrogen receptor modulator (SERM) originally developed for osteoporosis, also appears to have a major preventive effect on breast cancer incidence. Limitations in the design and patient population of raloxifene trials, however, have made it difficult to as yet recommend raloxifene for risk reduction of breast cancer. The randomized Study of Tamoxifen and Raloxifene (STAR) study, which will compare raloxifene to tamoxifen in over 20,000 postmenopausal women at increased risk of breast cancer, as well as ongoing and proposed placebo-controlled studies of tamoxifen, the aromatase inhibitor anastrazole, and other antiestrogens in high- or average-risk postmenopausal women, will provide further results on optimal prevention strategies.
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PMID:Breast cancer prevention with selective estrogen receptor modulators: a perspective. 1179 85

Although estrogens whose production is catalyzed by aromatase are considered to play a role in human breast carcinogenesis, it remains unclear whether aromatase expression occurs in ductal carcinoma in situ (DCIS) of the breast. Aromatase expression in 61 cases of pure DCIS and 101 cases of invasive ductal carcinoma (IDC) was investigated by immunohistochemical analysis using a polyclonal anti-aromatase antibody. The level of aromatase expression was semiquantified by the H-score which was estimated by the percentage of positive-staining cells and the intensity of staining. The levels of aromatase expression were compared between the DCIS and IDC samples, and were also compared among the tumor cells and stromal cells in the DCIS and IDC samples. Positive cytoplasmic staining for aromatase expression was found not only in stromal cells but also in tumor cells. The levels of aromatase expression in the tumor cells and stromal cells from the DCIS samples were significantly higher than those in the respective cells from the IDC samples. Among the DCIS samples, those specimens from patients of ages 50 years or over showed higher levels of aromatase expression in stromal cells, than those from patients below 50 years. The finding that significantly higher aromatase expression levels were found in DCIS than in IDC indicates that it may be possible to treat DCIS patients with aromatase inhibitors, especially as an adjuvant hormonal therapy for postmenopausal patients.
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PMID:Semi-quantitative immunohistochemical analysis of aromatase expression in ductal carcinoma in situ of the breast. 1215 Apr 52

Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti-estrogenic properties. Currently it is the most widely used agent for first line treatment against hormone sensitive metastatic breast cancer and the only approved hormonal agent for adjuvant treatment of organ confined breast cancer. Furthermore, its uses have been extended for the treatment of intraductal breast carcinoma patients. In such settings the most worrisome side effect of tamoxifen is its ability to increase the rates of uterine cancers. It has been claimed that most of these cancers are found at an early stage because of vaginal bleeding. Moreover, it has been shown that for most women transvaginal ultrasound is an ineffective screening method for the early detection of uterine carcinomas. It is important, however, to notice that long term tamoxifen treatment can cause metastatic uterine cancer--not only carcinomas but also sarcomas (mainly malignant mixed mesodermal tumors. It should be noted that, at least for the special population of BRCA mutation carriers, transvaginal ultrasound can increase our ability for the earlier discovery of ovarian cancer. Thus, we believe that there is still a place for the use of transvaginal ultrasound in special populations. This is specifically for long term tamoxifen users (more than the usually recommended five years), women with a higher chance of having uterine carcinomas (namely very high body weight, strong family history) and women with a high index of suspicion as carriers of a BRCA mutation. Until new second generation SERMs and aromatase inhibitors are shown to possess better anti-cancer abilities than tamoxifen, this drug will remain in wide use, however, we must not overlook its possible rare side effects.
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PMID:[Tamoxifen and breast cancer]. 1222 37

Tamoxifen has been used in the management of breast cancer for over 30 years. Since its introduction for the treatment of advanced breast cancer, its indications have increased to include the treatment of early breast cancer, ductal carcinoma in situ, and more recently for breast cancer chemoprevention. Tamoxifen has a good tolerability profile and moreover, unlike many other endocrine therapies, it is efficacious in both pre- and postmenopausal women. It is the combination of efficacy and tolerability that allows tamoxifen to maintain its position as the hormonal treatment of choice for most patients with oestrogen-receptor positive breast cancer. Ongoing studies will provide further information about the optimal duration of tamoxifen therapy and how it compares with the newer aromatase inhibitors.
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PMID:Tamoxifen ("Nolvadex"): a review. 1236 57

Anti-aromatase agents inhibit the cytochrome p-450 component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in peripheral tissues. These drugs can be classified into first-generation (e.g., aminoglutethimide), second-generation (e.g., formestane and fadrazole), and third-generation (e.g., anastrozole, letrozole, and exemestane) agents. Anti-aromatase agents can also be divided into type I and type II inhibitors. Type I inhibitors have a steroidal structure similar to androgens and inactivate the enzyme irreversibly by blocking the substrate-binding site, and are therefore known as aromatase inactivators. Type II inhibitors are nonsteroidal and their action is reversible. This article reviews the recent evidence regarding the role of third-generation aromatase inhibitors in the management of breast cancer. Relevant PubMed listed articles and presentations at recent international symposia were reviewed. There is a growing body of evidence supporting the role of third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) as first-line and second-line therapy for estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive advanced breast cancer in postmenopausal women, and as a neoadjuvant therapy in postmenopausal women with hormone receptor-positive invasive breast cancer unsuitable for breast-conserving surgery. Furthermore, the preliminary results of the ATAC (Arimidex, Tamoxifen, Alone and in Combination) study have shown that adjuvant anastrozole is superior to tamoxifen in terms of disease-free survival (DFS), adverse effects, and prevention of contralateral breast cancer in postmenopausal women with early, ER-positive breast cancer. However, longer follow-up is required to assess the long-term effects of these agents on bone mineral density, cognitive function, and overall survival prior to considering their routine use in the adjuvant setting instead of tamoxifen. The potential role of these drugs in the management of ductal carcinoma in situ (DCIS), premenopausal breast cancer, and breast cancer prevention is worth investigating.
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PMID:The evolving role of aromatase inhibitors in breast cancer. 1240 60

The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptor-positive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.
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PMID:The role of aromatase inhibitors in early breast cancer. 1259 39

Ductal carcinoma in situ (DCIS) accounts for approximately 20% of all screen-detected breast cancers. Total mastectomy can achieve a 98% cure rate in patients with DCIS, but its impact on quality of life should be weighed against the risk of local recurrence. Skin-sparing mastectomy with immediate reconstruction using autologous tissue can achieve excellent cosmesis and therefore should be considered when mastectomy is indicated. Nevertheless, mastectomy is considered an over-treatment for localized DCIS, and breast conservation is the goal of modern treatment. Three recent randomized controlled trials have demonstrated that adjuvant radiotherapy (RT) after adequate local excision of localized DCIS significantly reduces the incidence of local recurrence. Non-randomized studies suggest that patients with adequately excised small (<15 mm), non-high-grade DCIS not associated with necrosis can be safely spared adjuvant RT. However, this issue requires further evaluation in randomized controlled trials. The role of adjuvant tamoxifen is not well established, especially in relation to the hormone receptor status. Formal axillary dissection is not appropriate for DCIS; however, the potential role of the sentinel node biopsy (SNB) in selected high-risk cases requires further evaluation. The potential role of new selective estrogen receptor (ER) modulators and third-generation aromatase inhibitors in postmenopausal women with ER-positive DCIS, gene and protein expression profiling, and mammary ductoscopy will be the focus of future research.
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PMID:Current management of ductal carcinoma in situ of the breast. 1260 37

Ductal carcinoma in situ (DCIS) represents a spectrum of heterogenous disease that accounts for approximately one fifth of all screen-detected breast cancers and is considered as a precursor of invasive breast cancer if left untreated (35-50% risk). DCIS can be treated by total mastectomy with or without immediate breast reconstruction, local excision (LE) plus adjuvant radiotherapy (RT) or LE alone. Total mastectomy is associated with low rates of local recurrence (1.4%) and breast cancer-specific mortality (0.59%). Three recent randomized controlled trials (RCTs) have demonstrated that adjuvant RT after LE of localized DCIS significantly reduces the incidence of local recurrence. However these trials did not identify any subgroups of patients where RT could be safely omitted. Retrospective studies suggest that RT can be safely omitted after adequate LE (margin width > or =1 cm) of small (< 15 mm), non-high grade DCIS not associated with necrosis. Further RCTs are required to validate these retrospective findings, with an emphasis on standardized and meticulous tissue processing and pathological evaluation. The role of adjuvant tamoxifen in the management of DCIS continues to evolve. Formal axillary dissection is not appropriate for DCIS, however, the potential role of the sentinel node biopsy (SNB) in selected high risk cases requires further evaluation. The International Breast Cancer Intervention Study (IBIS-II) trial aims to evaluate the potential role of third generation aromatase inhibitors in postmenopausal women with hormone-sensitive DCIS.Future research will focus on the relevance of gene expression profiling, proteomics, Laser therapy and mammary ductoscopy to the management of DCIS.
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PMID:Towards optimal management of ductal carcinoma in situ of the breast. 1263 65

Current prevention trials have shown that tamoxifen can reduce the incidence of breast cancer by about 30%-40% in high-risk women, but that the risk of thromboembolic disease and endometrial cancer are increased about twofold. An alternative approach for postmenopausal women is to use an aromatase inhibitor to reduce oestrogen to very low levels. Data from the ATAC adjuvant trial indicate that the aromatase inhibitor anastrozole is more effective than tamoxifen in reducing recurrence and preventing new contralateral tumours, and also has a more favourable side-effect profile. This has led us to launch a new prevention trial--IBIS-II--in 6,000 high-risk postmenopausal women comparing anastrozole against placebo. A parallel trial will compare anastrozole against tamoxifen in 4,000 women with locally excised DCIS.
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PMID:Aromatase inhibitors in prevention--data from the ATAC (arimidex, tamoxifen alone or in combination) trial and the design of IBIS-II (the second International Breast Cancer Intervention Study). 1290 46


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