Breast Neoplasms: Vogel VG

Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, Morrow M, Runowicz C, Pritchard KI, Hagerty K, Arun B, Garber J, Vogel VG, Wade JL, Brown P, Cuzick J, Kramer BS, Lippman SM, Anonymous00092. · Cancer Policy and Clinical Affairs, 2318 Mill Rd, Suite 800, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #19470930 No free full text.

Abstract: PURPOSE To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) -positive invasive tumors. Women < or = 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, Halberg F, Somerfield MR, Davidson NE, Anonymous00080. · Virginia Commonwealth University/Massey Cancer Center, Richmond, VA, USA. · J Clin Oncol. · Pubmed #17033037 No free full text.

Abstract: PURPOSE: To update the 1999 American Society of Clinical Oncology (ASCO) guideline on breast cancer follow-up and management in the adjuvant setting. METHODS: An ASCO Expert Panel reviewed pertinent information from the literature through March 2006. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. RESULTS: The evidence supports regular history, physical examination, and mammography as the cornerstone of appropriate breast cancer follow-up. All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination. Examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose-positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination. CONCLUSION: Careful history taking, physical examination, and regular mammography are recommended for appropriate detection of breast cancer recurrence.

Smith TJ, Davidson NE, Schapira DV, Grunfeld E, Muss HB, Vogel VG, Somerfield MR. · American Society of Clinical Oncology, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #10071303 No free full text.

Abstract: OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors.

Vogel VG, Taioli E. · No affiliation provided · J Clin Oncol. · Pubmed #16567765 No free full text.

This publication has no abstract.

Vogel VG. · No affiliation provided · J Clin Oncol. · Pubmed #16260689 No free full text.

This publication has no abstract.

Vogel VG, Lo S. · No affiliation provided · J Natl Cancer Inst. · Pubmed #12529335 links to  free full text

This publication has no abstract.

Vogel VG. · No affiliation provided · J Clin Oncol. · Pubmed #11821438 No free full text.

This publication has no abstract.

Wickerham DL, Costantino JP, Vogel VG, Cronin WM, Cecchini RS, Ford LG, Wolmark N. · Operations Center, National Surgical Adjuvant Breast and Bowel Project, Allegheny Center, Pittsburgh, PA 15212, USA. · Recent Results Cancer Res. · Pubmed #19213563 No free full text.

Abstract: The NSABP Study of Tamoxifen and Raloxifene (STAR), launched in 1999, compared tamoxifen with raloxifene in a population of healthy postmenopausal women at increased risk for breast cancer to determine the relative effects on the risk of invasive breast cancer. To be eligible for participation, a woman had to be healthy with at least a 5-year predicted breast cancer risk of 1.66% based on the Gail model or a history of lobular carcinoma in situ (LCIS) treated by local excision alone. All participants were at least 35 years of age and postmenopausal. Between July 1999 and November 2004, 19,747 participants were randomized to receive either tamoxifen (20 mg, plus placebo) or raloxifene (60 mg, plus placebo) daily for a 5-year period. The mean age of the participants was 58.5 years; 93% were white and 51.6% had a hysterectomy prior to entering the study. Of the women, 71% had one or more first degree female relatives (mother, sister, daughter) with a history of breast cancer and 9.2% of the women had a personal history of LCIS. A history of atypical hyperplasia of the breast was noted in 22.7% of the participants. The mean predicted 5-year risk of developing breast cancer among the study population was 4.03% (SD, 2.17%) with a lifetime predicted risk of 16%. The mean time of follow-up is 3.9 years (SD, 1.6 years). There was no difference between the effect oftamoxifen and the effect of raloxifene on the incidence of invasive breast cancer; there were 163 cases of invasive breast cancer in the tamoxifen-treated group and 168 cases in those women assigned to raloxifene (incidence 4.30 per 1,000 vs 4.41 per 1,000; RR 1.02; 95% CI, 082-1.28). There were fewer cases of noninvasive breast cancer (LCIS and ductal carcinoma in situ [DCIS]) in the tamoxifen group (57 cases) than in the raloxifene group (80 cases), although the difference is not yet statistically significant (incidence 1.51 vs 2.11 per 1,000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 cases with raloxifene (RR, 0.63; 95% CI, 0.35-1.08).

Vogel VG. · University of Pittsburgh Cancer Institute, Magee-Womens Hospital, Pittsburgh, PA 15213-3180, USA. · Expert Rev Anticancer Ther. · Pubmed #19105706 No free full text.

Abstract: In the Study of Tamoxifen and Raloxifene (STAR) trial, postmenopausal women at increased risk of breast cancer received either oral tamoxifen (20 mg/day) or raloxifene (60 mg/day) over 5 years. There were an equal number of cases of invasive breast cancer in women assigned to tamoxifen and raloxifene. There were fewer cases of noninvasive breast cancer in the tamoxifen group than in the raloxifene group (risk ratio [RR]: 1.40; 95% confidence interval [CI]: 0.98-2.02). There were more cases of uterine cancer with tamoxifen than with raloxifene (RR: 0.62; 95% CI: 0.35-1.08). Thromboembolic events occurred less often in the raloxifene group (RR: 0.70; 95% CI: 0.54-0.91) and there were fewer cataracts and cataract surgeries in the women taking raloxifene (RR: 0.79; 95% CI: 0.68-0.92). The STAR trial has shown that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of adverse events but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease and stroke is similar for both drugs.

Vogel VG. · Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Menopause. · Pubmed #18596599 No free full text.

Abstract: Breast cancer risk factors have been studied for the past three decades, and the single most important risk factor is age. Hormonally linked adult reproductive and anthropometric risk factors contribute to the etiology of postmenopausal breast cancer. The risk of breast cancer increases among women older than 50 years of age who have benign breast disease, especially those with atypical ductal or lobular hyperplasia. Lobular carcinoma in situ increases risk significantly, as do a family history of breast cancer in first-degree relatives and the presence of BRCA1 or BRCA2 mutations. Diet, exercise, and environmental factors play a very small role in overall risk. Mammographic breast density increases relative risk fivefold among women with the highest density, and breast cancer risk is two to three times greater in women with elevated serum levels of estradiol or testosterone. Multivariate risk models allow determination of composite relative risks and cumulative lifetime risk, although improved models for African American women are required. For postmenopausal women, newer risk models are being developed and validated that include age, breast density, race, ethnicity, family history of breast cancer, a previous breast biopsy, body mass index, age at onset of natural menopause, hormone therapy, and previous false-positive mammography. A simpler model that includes only age, breast cancer in first-degree relatives, and previous breast biopsy performs well for estrogen receptor-positive breast cancer in postmenopausal women. As many as 10 million women in the United States are at increased risk, and clinicians are obligated to identify these women and manage their risk appropriately.

Vogel VG. · Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pennsylvania, USA. · Oncology (Williston Park). · Pubmed #18561555 No free full text.

Abstract: Several large, prospective trials have evaluated tamoxifen compared with placebo for breast cancer risk reduction in women at increased risk for breast cancer. Analysis of the large, prospective breast cancer risk-reduction trials that used tamoxifen estimated that tamoxifen decreased breast cancer incidence by 38% on average and estrogen receptor-positive tumors by 48%. Tamoxifen is known to have several serious side effects, including uterine malignancy, thromboembolic events, cataracts, and menopausal symptoms, that have limited its usefulness in the risk-reduction setting. Raloxifene (Evista) is a benzothiophene selective estrogen-receptor modulator that has antiestrogenic effects on breast and endometrial tissue as well as estrogenic effects that are similar to but distinct from tamoxifen. Among postmenopausal women who are at increased risk for breast cancer, raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer but appears to be less effective than tamoxifen in reducing the risk of in situ breast cancer. Raloxifene causes less benign and malignant uterine changes and fewer thromboembolic events than tamoxifen. Symptomatic side effects are comparable for the two drugs. Raloxifene is more appropriate than tamoxifen for reduction of breast cancer risk among postmenopausal women at increased risk for breast cancer.

Reeder JG, Vogel VG. · Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. · Cancer Treat Res. · Pubmed #18274088 No free full text.

This publication has no abstract.

Reeder JG, Vogel VG. · Division of Hematology/Oncology, University of Pittsburgh Medical Center Cancer Pavilion, PA 15232, USA. · Clin Breast Cancer. · Pubmed #18269772 No free full text.

Abstract: Breast cancer is a devastating illness that affects tens of thousands of American women each year. Although no one can predict who will actually develop breast cancer, a number of risk factors have been found that allow clinicians to identify the women at highest risk. Recent research has focused on exploring options, such as chemoprevention, to prevent high-risk women from developing breast cancer. The selective estrogen receptor (ER) modulators (SERMs) were a logical choice for chemoprevention because of their well-known estrogen antagonist effects in the breast. Tamoxifen is the best studied of these agents and has been shown to reduce the incidence of all breast cancers by 38% and ER-positive tumors by 48%.(1) However, despite this large potential risk reduction, risk management with chemopreventive agents is still not routine. The primary deterrents are believed to be the significant adverse events associated with tamoxifen as well as a perceived decline in quality of life (QOL).(2-4) These concerns led researchers to consider other possible agents that would still be effective but would have fewer or more acceptable side effects than tamoxifen. Raloxifene was proposed as an alternative to tamoxifen based on its estrogen antagonist effects in the breast and its relative safety as an osteoporosis agent. In this article, we will review the trials that led to the emergence of both tamoxifen and raloxifene as chemopreventive agents and will then offer a management strategy for breast cancer prevention in the primary care setting.

Vogel VG. · Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213-3180, USA. · Curr Treat Options Oncol. · Pubmed #17634835 No free full text.

Abstract: OPINION STATEMENT: Several large, prospective trials have evaluated tamoxifen compared with placebo for breast cancer risk reduction in women at increased risk for breast cancer. The risk of developing breast cancer is the primary determinant of net benefit, with greater net benefits accruing to women with the highest risk of breast cancer. Both age and the presence of factors that increase the risk of toxicity have the greatest effect on the net benefit associated with tamoxifen. The greatest clinical benefit with least side effects is derived from the use of tamoxifen in younger, premenopausal women who are less likely to have thromboembolic complications and uterine cancer, in women without a uterus, and in women at higher breast cancer risk such as those with atypical hyperplasia or lobular carcinoma in situ. Tamoxifen may offer benefit to women who are carriers of BRCA2 mutations, although no prospective trials have been conducted. Compared to placebo in postmenopausal women at average risk of breast cancer in published trials of osteoporosis, raloxifene reduces the risk of invasive breast cancer. Among younger postmenopausal women who are at increased risk of breast cancer, raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. Raloxifene appears to be less effective than tamoxifen in reducing the risk of in situ breast cancer. In high-risk, younger, postmenopausal women, raloxifene appears to offer net benefit when comparing reduction of the risk of breast cancer and the prevention of fractures with the risk of stroke, venous thromboembolic events, uterine events, as well as symptomatic side effects.

Newman LA, Vogel VG. · Breast Care Center, 1500 East Medical Center Drive, 3308 CGC, University of Michigan, Ann Arbor, MI 48109, USA. · Surg Clin North Am. · Pubmed #17498528 No free full text.

Abstract: Until recently, the primary message of breast health awareness programs was that early detection is a woman's best protection against breast cancer, because there was no way to prevent it. Currently, however, tamoxifen is approved for chemoprevention of breast cancer in high-risk women, and studies are underway evaluating other medications that may decrease breast cancer risk. Data have also become available regarding the efficacy of surgical strategies to reduce breast cancer risk. Any prevention method, however, will have associated risk of complications or adverse effects, and determining the net risk/benefit ratio depends on the ability to accurately quantify a woman's baseline likelihood of developing breast cancer. This article reviews available methods for assessing and reducing breast cancer risk.

Vogel VG. · Magee-Womens Hospital, 300 Halket Street, Pittsburgh, PA 15213-3180, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #17057026 links to  free full text

Abstract: BACKGROUND: The average age of the U.S. population is increasing, and cancer incidence increases with age. Both improved early detection of first malignancies and effective primary oncologic therapy have led to prolonged survival, and the risk of secondary malignancies has consequently increased. A few anatomic sites are at increased risk for second malignancies within the same organ: breast, colon and rectum, lung, head and neck (or upper aerodigestive malignancies), prostate, and the uterine cervix. Some of the cancers also incur a risk for a second malignancy at another anatomic site. In addition, there are well-described clinical genetic syndromes that, as unique clinical entities, predispose to second malignant tumors. METHODS/RESULTS: In this review, we focus on issues related to the risk of second malignancies among patients with primary breast, colon, lung and head and neck, prostate, and cervical cancers that comprise the most common sites of primary malignancy among patients in the United States. We review recent data related to both established and new screening strategies at these sites. CONCLUSIONS: There is some evidence that screening will improve outcomes among patients who may develop second malignancies, although the data are limited. The optimal screening modalities and strategies to reduce mortality from second malignancies remain to be defined for most tumor sites.

Geller BA, Vogel VG. · Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. · Breast Dis. · Pubmed #16917141 No free full text.

Abstract: In the United States, an estimated 211,240 new cases of breast cancer were diagnosed in 2005 and approximately 40,410 deaths occurred. In recent years, a number of randomized prospective trials have investigated the use of antiestrogens as a means to reduce the incidence of breast cancer. We aim to describe the results of these trials as they pertain to postmenopausal women. In the Breast Cancer Prevention Trial and the International Breast Cancer Intervention Study-I, tamoxifen reduced the risk of invasive breast cancer by 55% and 30%, respectively, among older participants. However, tamoxifen is associated with adverse events including thromboembolic disease and endometrial cancer. The Multiple Outcomes of Raloxifene Evaluation, aimed primarily at evaluating the use of raloxifene for the prevention of osteoporosis, demonstrated a 72% decreased breast cancer risk. Side effects of raloxifene include thromboembolic events, but not endometrial cancer. Results from the Study of Tamoxifen and Raloxifene trial comparing these two agents are expected in mid-2006. Ongoing chemoprevention trials are evaluating the use of the aromatase inhibitors. At present, tamoxifen is the only FDA-approved agent for breast cancer risk reduction. Decisions regarding its use must remain highly individualized, involving careful consideration of its risks versus benefits.

Kapoor A, Vogel VG. · University of Pittsburgh School of Medicine, Department of Medicine, Magee-Womens Hospital, 300 Halket Street, Room 3524, Pittsburgh, PA 15213-3180, USA. · Expert Rev Anticancer Ther. · Pubmed #15877524 No free full text.

Abstract: Breast cancer is the second leading cause of cancer deaths in US women today. This year, approximately 216,000 US women will be diagnosed with invasive breast cancer and another 60,000 with in situ disease. Numerous factors can quantify individual risks for breast cancer, guide therapy and predict outcome. This review focuses on the clinical, pathologic, molecular and genetic prognostic tools available for use in patients with breast cancer, and their impact on clinical decisions and treatment selection.

Hollingsworth AB, Singletary SE, Morrow M, Francescatti DS, O'Shaughnessy JA, Hartman AR, Haddad B, Schnabel FR, Vogel VG. · Department of Surgery, Mercy Health Center, Mercy Women's Center, 4300 McAuley Blvd., Oklahoma City, OK 73120, USA. · Am J Surg. · Pubmed #15006563 No free full text.

Abstract: The potential for reducing the risk of breast cancer through selective estrogen receptor modulators, aromatase inhibitors, and surgery has generated interest in the use of quantitative models of risk assessment. With the addition of ductal lavage cytology to traditional epidemiologic risk factors, a discovery of cellular atypia can result in refinement of assigned risk values, while simultaneously optimizing patient selection for selective estrogen receptor modulators utilization. In view of increasing complexity in this arena, a Risk Assessment Working Group was formed to outline management strategies for the patient at an elevated risk for the development of breast cancer. No longer a statistical exercise, quantitative risk assessment is part of basic breast care and comprehensive management includes a discussion of the following: ductal lavage for improved risk stratification, multiple options for risk reduction, and high risk surveillance strategies that might incorporate investigational imaging protocols.

Vogel VG. · University of Pittsburgh, Cancer Institute/Magee-Womens Hospital, Pittsburgh, Pennsylvania 15213-3180, USA. · Diagn Cytopathol. · Pubmed #14986294 No free full text.

Abstract: Proliferative disease accounts for as much as one-third of all biopsies for benign disease and 5-10% of proliferative lesions show atypia ductal or lobular hyperplasia. Nearly 40% of women with a family history of breast cancer and atypical hyperplasia subsequently develop breast cancer. A quantitative model developed by Gail and colleagues estimates the probability of developing breast cancer over time. Risk factors in the model include current age, ages at menarche and first live birth, number of previous biopsies, the presence of cellular atypia, and the number of first-degree relatives with breast cancer. Atypical hyperplasia approximately doubles the risk of developing invasive breast cancer within any quantitative risk profile. Ductal lavage provides a minimally invasive method of collecting breast epithelial cells. The procedure opens the possibility of repeatable tracking of breast cytology over time, but its role as a risk assessment tool remains to be fully defined.

Thull DL, Vogel VG. · Magee/UPCI Breast Cancer Genetics Program, Magee-Women's Hospital, Pittsburgh, Pennsylvania 15213, USA. · Oncologist. · Pubmed #14755011 links to  free full text

Abstract: Clinicians should recognize the genetic syndromes that predispose to the development of breast cancer so that patients may be afforded the opportunity to have genetic testing to assist them and their family members in making medical management decisions. Approximately 80%-90% of hereditary breast cancer cases are caused by mutations in the BRCA1 and BRCA2 genes. Other important clinical genetic predispositions include Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, and ataxia-telangiectasia. The key to identifying women who are at risk for a hereditary breast cancer lies in obtaining an adequate, three-generation family history, including ethnic background. For unaffected women, breast cancer risks can be estimated using the quantitative models of Gail and Claus, but there are limitations to these models. Other quantitative models predict the likelihood that a patient is carrying a mutated gene. Genetic testing is available at selected laboratories for each of the hereditary syndromes described, and there are three possible outcomes to testing. These outcomes and their management implications are described in detail. Clinical management options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic surgery. Application of these principles can reduce morbidity in women with genetic predispositions to breast cancer.

Lo SS, Vogel VG. · Section of Hematology/Oncology, Department of Medicine, Magee/University of Pittsburgh Cancer Institute Breast Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Best Pract Res Clin Endocrinol Metab. · Pubmed #14687600 No free full text.

Abstract: Breast cancer remains the most common malignancy in women worldwide. Oestrogen levels appear to be associated with an increased risk for the development of breast cancer. The Early Breast Cancer Trialists' Cooperative Group reported in a 1998 meta-analysis of 37000 breast cancer patients in 55 randomized adjuvant trials that tamoxifen, a selective oestrogen receptor modulator, reduced the incidence of contralateral breast cancers by 47% at 5 years. Tamoxifen has been shown in numerous prevention studies to decrease the incidence of breast cancer in high-risk women. Overall, the tamoxifen prevention trials showed a 38% reduction in the incidence of breast cancer (95% CI 28-46; P<0.0001). In the largest risk-reduction trial, the Breast Cancer Prevention Trial conducted by the National Surgical Adjuvant Breast and Bowel Project, tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<0.00001), and non-invasive breast cancer by 50% (P<0.002). The occurrence of oestrogen receptor-(OR)-positive tumours decreased by 69%. Tamoxifen reduces the risk of developing oestrogen receptor-positive tumours, but OR-negative tumours are not affected. Rare but life-threatening side-effects of tamoxifen include endometrial carcinoma, thromboembolic events and cerebrovascular events. Less serious side-effects include cataracts, vasomotor instability, nausea and vaginal discharge. Raloxifene, a second-generation selective oestrogen receptor modulator, is approved for treatment of osteoporosis in post-menopausal women in the USA but it is not currently approved for breast cancer prevention outside of a clinical trial. Prevention studies involving raloxifene and aromatase inhibitors are currently being conducted.

Vogel VG. · University of Pittsburgh, Department of Medicine, 3550 Terrace Street, Scaife 1218, Pittsburgh PA 15261, USA. · Surg Clin North Am. · Pubmed #12875593 No free full text.

Abstract: Comprehensive breast cancer risk management is a practical tool that can now be regarded as a necessary clinical component of women's health. Risk assessment is the starting point for counseling women about risk, and it facilitates rational decision-making about prophylactic surgery, initiation of screening at an early age, and initiating preventive interventions. The availability of risk assessment models permit rapid risk calculation during routine clinical encounters, and risk profiles can be easily updated at subsequent clinical visits. Clinicians can now incorporate risk assessment and management into their routine screening and health maintenance appointments. Additional prospective clinical trials should be conducted to define the optimal use of existing management strategies, develop refined risk assessment instruments that incorporate additional risk-factor information, and evaluate populations for whom validated risk-assessment approaches do not yet exist.

Rastogi P, Vogel VG. · Breast Cancer Prevention Program, Magee-Women's Hospital/University of Pittsburgh, Department of Medicine, Section of Hematology/Oncology, School of Medicine, Pittsburgh, Pennsylvania, USA. · Oncology (Williston Park). · Pubmed #12846124 No free full text.

Abstract: Four randomized prospective trials have evaluated tamoxifen for chemoprevention of breast cancer. The National Surgical Adjuvant Breast and Bowel Project P-1 trial reported that tamoxifen reduced the risk of invasive breast cancer by 49%. Two smaller European trials, the Royal Marsden Hospital Chemoprevention Trial and the Italian Tamoxifen Prevention Study, demonstrated no decrease in the incidence of breast cancer among women using tamoxifen. The International Breast Cancer Intervention Study confirmed that tamoxifen can reduce the risk of breast cancer in healthy women. The Multiple Outcomes of Raloxifene Evaluation trial, which evaluated the use of raloxifene (Evista) to prevent osteoporosis, found that the risk of invasive breast cancer decreased by 76%. A uniform theme in these trials is that tamoxifen reduces the risk of breast cancer among women at high risk for the disease. Tamoxifen is currently approved for breast cancer risk reduction. However, because of the side effects associated with its use (i.e., endometrial cancer and thromboembolism), other agents are being investigated. The Study of Tamoxifen and Raloxifene is designed to compare the efficacy of tamoxifen and raloxifene in reducing breast cancer risk. Aromatase inhibitors will also be studied in the setting of chemoprevention for breast cancer.

Vogel VG, Costantino JP, Wickerham DL, Cronin WM. · University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-3180, USA. · Clin Cancer Res. · Pubmed #12538506 links to  free full text

Abstract: Following up on the results of recent completed trials, several major breast cancer prevention trials are either underway or impending. In the Study of Tamoxifen and Raloxifene trial, eligible women are at least 35 years of age and postmenopausal, with either lobular carcinoma in situ or a 5-year risk of invasive breast cancer of at least 1.67%. The study will compare the ability of 5 years of tamoxifen or raloxifene to reduce the incidence of breast cancer. Subjects are randomly assigned to receive either 20 mg of tamoxifen or 60 mg of raloxifene daily. After 3 years of recruitment, 13647 women have been randomized (20.7% of those eligible). The median age of randomized women is 58 years (mean age, 58 years), and their median 5-year risk of breast cancer is 3.3% (mean 5-year risk of breast cancer, 4.0%). Hysterectomy was reported by 52.5% of the randomized women; lobular carcinoma in situ was reported by 8.4% of subjects before randomization. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial, 1804 women with ductal carcinoma in situ were randomly assigned tamoxifen after lumpectomy and radiation therapy. Women in the tamoxifen group had fewer breast cancer events at 5 years than did those on placebo (8.2% versus 13.4%, P = 0.0009). The proposed NSABP B-35 trial will have the same design as NSABP B-24 but will compare tamoxifen with anastrozole in postmenopausal women. Outcomes will include both ipsilateral and contralateral new breast cancer and recurrences, as well as the occurrence of regional and distant disease. Enrollment will begin in early 2003.