Breast Neoplasms: Carlson RW

Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smith ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC, Anonymous00042. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #19200416 No free full text.

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El Saghir NS, Eniu A, Carlson RW, Aziz Z, Vorobiof D, Hortobagyi GN, Anonymous00023. · Division of Hematology-Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. nagi.saghir@ aub.edu.lb · Cancer. · Pubmed #18837023 No free full text.

Abstract: The management of locally advanced breast cancer (LABC) is guided by scientific advances but is limited by local resources and expertise. LABC remains very common in low-resource countries. The Systemic Therapy Focus Group met as part of the Breast Health Global Initiative (BHGI) Summit in Budapest, Hungary, in October 2007 to discuss management and implementation of primary systemic therapy (PST) for LABC. PST is standard treatment for large operable breast cancer in enhanced-resource settings and, in all resource settings, should be standard treatment for inoperable breast cancer and for LABC. Standard PST includes anthracycline-based chemotherapy. The addition of sequential taxanes after anthracycline improves pathologic responses and breast-conservation rates and is appropriate at enhanced-resource levels; however, costs and lack of clear survival benefit do not justify their use at limited-resource levels. It remains to define better the role of endocrine therapy as PST, but it is acceptable in elderly women. Aromatase inhibitors have produced better results than tamoxifen in postmenopausal patients and are used in enhanced-resource settings. The less expensive tamoxifen remains useful in low-resource countries. Trastuzumab combined with chemotherapy yields high pathologic response rates in patients with HER2/neu-overexpressing tumors; its use in low-resource countries is limited by high costs. Most studies on PST of LABC were conducted in countries with enhanced resources. BHGI encourages conducting clinical trials in countries with limited resources.

Eniu A, Carlson RW, El Saghir NS, Bines J, Bese NS, Vorobiof D, Masetti R, Anderson BO, Anonymous00019. · Department of Breast Tumors, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania. · Cancer. · Pubmed #18837019 No free full text.

Abstract: A key determinant of breast cancer outcome is the degree to which newly diagnosed cancers are treated correctly in a timely fashion. Available resources must be applied in a rational manner to optimize population-based outcomes. A multidisciplinary international panel of experts addressed the implementation of treatment guidelines and developed process checklists for breast surgery, radiation treatment, and systemic therapy. The needed resources for stage I, stage II, locally advanced, and metastatic breast cancer were outlined, and process metrics were developed. The ability to perform modified radical mastectomy is the mainstay of locoregional treatment at the basic level of breast healthcare. Radiation therapy allows for consideration of breast-conserving therapy, postmastectomy chest wall irradiation, and palliation of painful or symptomatic metastases. Systemic therapy with cytotoxic chemotherapy is effective in the treatment of all biologic subtypes of breast cancer, but its provision is resource intensive. Although endocrine therapy requires few specialized resources, it requires knowledge of hormone receptor status. Targeted therapy against human epidermal growth factor receptor 2 (anti-HER-2) is very effective in tumors that overexpress HER-2/neu receptors, but cost largely prevents its use in resource-limited environments. Incremental allocation of resources can help address economic disparities and ensure equity in access to care. Checklists and allocation tables can support the objective of offering optimal care for all patients. The use of process metrics can facilitate the development of multidisciplinary, integrated, fiscally responsible, continuously improving, and flexible approaches to the global enhancement of breast cancer treatment.

Bevers TB, Armstrong DK, Arun B, Carlson RW, Cowan KH, Daly MB, Fleming I, Garber JE, Gemignani M, Gradishar WJ, Krontiras H, Kulkarni S, Laronga C, Lawton T, Loftus L, Macdonald DJ, Mahoney MC, Merajver SD, Seewaldt V, Sellin RV, Shapiro CL, Singletary E, Ward JH, Anonymous00155. · National Comprehensive Cancer Network · J Natl Compr Canc Netw. · Pubmed #17927926 No free full text.

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Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ, Hudis CA, Jahanzeb M, Stark A, Wolff AC, Press MF, Winer EP, Paik S, Ljung BM, Anonymous00047. · Stanford Hospital and Clinics. · J Natl Compr Canc Netw. · Pubmed #16813731 No free full text.

Abstract: The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

Carlson RW, Brown E, Burstein HJ, Gradishar WJ, Hudis CA, Loprinzi C, Mamounas EP, Perez EA, Pritchard K, Ravdin P, Recht A, Somlo G, Theriault RL, Winer EP, Wolff AC, Anonymous00401. · Stanford Hospital and Clinics, Stanford University, Stanford, CA, USA. · J Natl Compr Canc Netw. · Pubmed #16507275 No free full text.

Abstract: The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

Eniu A, Carlson RW, Aziz Z, Bines J, Hortobágyi GN, Bese NS, Love RR, Vikram B, Kurkure A, Anderson BO, Anonymous00017. · Department of Breast Tumors, Oncology, Cancer Institute I. Chiricuta, Cluj-Napoca, Romania. · Breast J. · Pubmed #16430398 No free full text.

Abstract: Treating breast cancer under the constraints of significantly limited health care resources poses unique challenges that are not well addressed by existing guidelines. We present evidence-based guidelines for systematically prioritizing cancer therapies across the entire spectrum of resource levels. After consideration of factors affecting the value of a given breast cancer therapy (contribution to overall survival, disease-free survival, quality of life, and cost), we assigned each therapy to one of four incremental levels--basic, limited, enhanced, or maximal--that together map out a sequential and flexible approach for planning, establishing, and expanding breast cancer treatment services. For stage I disease, basic-level therapies are modified radical mastectomy and endocrine therapy with ovarian ablation or tamoxifen; therapies added at the limited level are breast-conserving therapy, radiation therapy, and standard-efficacy chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF], or doxorubicin and cyclophosphamide [AC], epirubicin and cyclophosphamide [EC], or 5-fluorouracil, doxorubicin, and cyclophosphamide [FAC]); at the enhanced level, taxane chemotherapy and endocrine therapy with aromatase inhibitors or luteinizing hormone-releasing hormone (LH-RH) agonists; and at the maximal level, reconstructive surgery, dose-dense chemotherapy, and growth factors. For stage II disease, the therapy allocation is the same, with the exception that standard-efficacy chemotherapy is a basic-level therapy. For locally advanced breast cancer, basic-level therapies are modified radical mastectomy, neoadjuvant chemotherapy (CMF, AC, or FAC), and endocrine therapy with ovarian ablation or tamoxifen; the therapy added at the limited level is postmastectomy radiation therapy; at the enhanced level, breast-conserving therapy, breast-conserving whole-breast radiation therapy, taxane chemotherapy, and endocrine therapy with aromatase inhibitors or LH-RH agonists; and at the maximal level, reconstructive surgery and dose-dense chemotherapy and growth factors. For metastatic or recurrent disease, basic-level therapies are total mastectomy for ipsilateral in-breast recurrence, endocrine therapy with ovarian ablation or tamoxifen, and analgesics; therapies added at the limited level are radiation therapy and CMF or anthracycline chemotherapy; at the enhanced level, chemotherapy with taxanes, capecitabine, or trastuzumab, endocrine therapy with aromatase inhibitors, and bisphosphonates; and at the maximal level, chemotherapy with vinorelbine, gemcitabine, or carboplatin, growth factors, and endocrine therapy with fulvestrant. Compared with the treatment of early breast cancer, the treatment of advanced breast cancer is more resource intensive and generally has poorer outcomes, highlighting the potential benefit of earlier detection and diagnosis, both in terms of conserving scarce resources and in terms of reducing morbidity and mortality. Use of the scheme outlined here should help ministers of health, policymakers, administrators, and institutions in limited-resource settings plan, establish, and gradually expand breast cancer treatment services for their populations.

Carlson RW, Anderson BO, Burstein HJ, Cox CE, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis C, Jahanzeb M, Ljung BM, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC, Anonymous00249. · Stanford Hospital & Clinics, USA. · J Natl Compr Canc Netw. · Pubmed #16002000 No free full text.

This publication has no abstract.

Carlson RW, Edge SB, Theriault RL, Anonymous00376. · Stanford University Medical Center, USA. · Cancer Control. · Pubmed #11760559 No free full text.

Abstract: The 2001 NCCN Breast Cancer Guidelines reflect the results of 5 generations of NCCN Breast Cancer Guidelines. Evidence-based guidelines, such as the NNCN Breast Cancer Guidelines, are possible only because of the availability of high-level evidence at multiple decision points in treatment. The continued performance of high quality clinical trials is central to our ability to further improve the treatment of breast cancer. The panel believes that participation in high quality clinical trials is the preferred treatment at all points in breast cancer therapy.

Carlson RW, Anderson BO, Bensinger W, Cox CE, Davidson NE, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Lichter AS, McCormick B, Nabell LM, Reed EC, Silver SM, Smith ML, Somlo G, Theriault R, Ward JH, Winer EP, Wolff A, Anonymous00205. · Stanford Hospital and Clinics, Palo Alto, CA, USA. · Oncology (Williston Park). · Pubmed #11195418 No free full text.

Abstract: The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients.

Carlson RW, Moench S, Hurria A, Balducci L, Burstein HJ, Goldstein LJ, Gradishar WJ, Hughes KS, Jahanzeb M, Lichtman SM, Marks LB, McClure JS, McCormick B, Nabell LM, Pierce LJ, Smith ML, Topham NS, Traina TA, Ward JH, Winer EP. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #18597715 No free full text.

Abstract: Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.

Telli ML, Hunt SA, Carlson RW, Guardino AE. · Department of Medicine, Division of Medical Oncology, Stanford University, Stanford, CA, USA. · J Clin Oncol. · Pubmed #17687157 No free full text.

Abstract: PURPOSE: To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials. DESIGN: The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context. RESULTS: Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%. CONCLUSION: Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2-positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

Anderson BO, Carlson RW. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA 98195, USA. · J Natl Compr Canc Netw. · Pubmed #17439764 No free full text.

Abstract: Breast cancer is an increasingly urgent problem in low- and mid-level resource regions of the world. Despite knowing the optimal management strategy based on guidelines developed in wealthy countries, clinicians are forced to provide less-than-optimal care when diagnostic or treatment resources are lacking. For this reason, it is important to identify which resources most effectively fill health care needs in limited-resource regions, where patients commonly present with more advanced disease at diagnosis, and to provide guidance on how new resource allocations should be made to maximize improvement in outcome. Established in 2002, the Breast Health Global Initiative (BHGI) created an international health alliance to develop evidence-based guidelines for countries with limited resources to improve breast health outcomes. The BHGI serves as a program for international guideline development and as a hub for linkage among clinicians, governmental health agencies, and advocacy groups to translate guidelines into policy and practice. The BHGI collaborated with 12 national and international health organizations, cancer societies, and nongovernmental organizations to host 2 BHGI international summits. The evidence-based BHGI guidelines, developed at the 2002 Global Summit, were published in 2003 as a theoretical treatise on international breast health care. These guidelines were then updated and expanded at the 2005 Global Summit into a fully comprehensive and flexible framework to permit incremental improvements in health care delivery, based on outcomes, cost, cost-effectiveness, and use of health care services.

Telli ML, Horst KC, Guardino AE, Dirbas FM, Carlson RW. · Department of Medicine, Stanford University, Stanford, CA, USA. · J Natl Compr Canc Netw. · Pubmed #17439760 No free full text.

Abstract: Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a wide range of clinical behavior. These tumors are categorized as benign, borderline, or malignant based on a combination of histologic features. The prognosis of phyllodes tumors is favorable, with local recurrence occurring in approximately 15% of patients overall and distant recurrence in approximately 5% to 10% overall. Wide excision with a greater than 1 cm margin is definitive primary therapy. Adjuvant systemic therapy is of no proven value. Patients with locally recurrent disease should undergo wide excision of the recurrence with or without subsequent radiotherapy.

Carlson RW, Anderson BO, Burstein HJ, Carter WB, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Ljung BM, Kiel K, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC. · National Comprehensive Cancer Network · J Natl Compr Canc Netw. · Pubmed #17439758 No free full text.

This publication has no abstract.

Carlson RW, Hudis CA, Pritchard KI, Anonymous00094, Anonymous00095, Anonymous00096. · Department of Medicine, Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305-5826, USA. · J Natl Compr Canc Netw. · Pubmed #17112447 No free full text.

Abstract: Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.

Horst KC, Smitt MC, Goffinet DR, Carlson RW. · Department of Radiation Oncology, Stanford University, CA 94305, USA. · Clin Breast Cancer. · Pubmed #15748463 No free full text.

Abstract: Breast-conserving therapy (BCT) is a proven local treatment option for select patients with early-stage breast cancer. This paper reviews pathologic, clinical, and treatment-related features that have been identified as known or potential predictors for ipsilateral breast tumor recurrence in patients treated with BCT. Pathologic risk factors such as the final pathologic margin status of the excised specimen after BCT, the extent of margin involvement, the interaction of margin status with other adverse features, the role of biomarkers, and the presence of an extensive intraductal component or lobular carcinoma in situ all impact the likelihood of ipsilateral breast tumor recurrence. Predictors of positive repeat excision findings after conservative surgery include young age, presence of an extensive intraductal component, and close or positive margins in prior excision. Finally, treatment-related factors predicting ipsilateral breast tumor recurrence include extent of breast radiation therapy, use of a boost to the lumpectomy cavity, use of tamoxifen or chemotherapeutic agents, and timing of systemic therapy with irradiation. The ability to predict for an increased risk of ipsilateral breast tumor recurrence enhances the ability to select optimal local treatment strategies for women considering BCT.

Mollick JA, Carlson RW. · Department of Medicine, Division of Medical Oncology, Stanford University, Stanford, CA 94305, USA. · Breast Dis. · Pubmed #15687722 No free full text.

Abstract: The majority of women with early stage breast cancers are successfully treated with surgery, radiation therapy and adjuvant systemic therapy. However, 30% of all Stage I and Stage II patients can be expected to experience a relapse. The belief that early detection of recurrences can lead to an increase in survival has been used to justify intensive follow-up regimens following primary treatment of patients with early stage disease. However, the vast majority of data support a program of scheduled surveillance visits and demonstrate that a comprehensive history and physical examination is as efficacious as programs utilizing intensive testing and imaging procedures in the asymptomatic patient. Screening mammography to detect ipsilateral in-breast recurrence or a new primary cancer in the contralateral breast is the only imaging study that is recommended for routine surveillance. Knowledge of the natural history of breast cancer, risk factors for relapse, and the symptoms and physical findings commonly associated with recurrence are central to efficiently and effectively monitoring this cohort of women in clinical practice.

Chung CT, Carlson RW. · Division of Oncology, Stanford University, CA 94305, USA. · Clin Breast Cancer. · Pubmed #15347435 No free full text.

Abstract: Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.

Chung CT, Carlson RW. · Division of Oncology, Stanford University, Stanford, California, USA. · Oncologist. · Pubmed #14657529 links to  free full text

Abstract: Patients with metastatic breast cancer consist of a heterogeneous group of patients whose prognoses and clinical courses can vary depending on host factors, such as comorbidity and age, and on tumor factors, such as hormone-receptor status, grade, and anatomical site of disease. Although the median survival time for patients with metastatic breast cancer is 2-4 years, subsets of patients with either indolent or limited metastatic disease may have prolonged survival times. Further, expectations of treatment, both in terms of efficacy and of toxicity, vary greatly based upon the specific treatment, patient characteristics, and tumor characteristics. Thus, the goals of treatment for patients with metastatic breast cancer are influenced by estimates of prognoses as well as a balance between physician and patient preferences regarding efficacy and toxicity considerations. Traditionally, objective measures of response and survival have been the targeted end points in clinical trial design and in physician selection of therapy for metastatic breast cancer. More recently, issues of quality of life have surfaced as important end points, especially from the perspective of the patient. The decision-making process in selecting the optimal treatment for patients with metastatic breast cancer is, therefore, a multidimensional process involving subjective as well as objective goals of treatment. Ultimately, the benefits of treatment must justify the risks and toxicities of the treatment, and the impact of treatment should be measured in relation to specified goals. Both physician and patient perspectives are important in establishing the objectives of treatment, and this process is optimally an interactive and ongoing process throughout the course of disease.

Carlson RW, Henderson IC. · Department of Medicine, Stanford University, Palo Alto, CA 94304, USA. · Breast Cancer Res Treat. · Pubmed #14535531 No free full text.

Abstract: The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.

Allred DC, Baum M, Buzdar AU, Carlson RW, Dowsett M, Elledge RM, Gradishar WJ, Grana G, Howell A, Mamounas EP. · Baylor College of Medicine, Houston, Texas, USA. · Breast J. · Pubmed #12752630 No free full text.

Abstract: This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second-line therapy in postmenopausal women with hormone-responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first-line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease.

Anderson BO, Braun S, Carlson RW, Gralow JR, Lagios MD, Lehman C, Schwartsmann G, Vargas HI. · Department of Surgery, University of Washington, Seattle, Washington 98195, USA. · Breast J. · Pubmed #12713496 No free full text.

Abstract: Among women around the globe, breast cancer is both the most common cancer and the leading cause of cancer-related death. Women in economically disadvantaged countries have a lower incidence of breast cancer, but poorer survival rates for the disease relative to women in affluent countries. Evidence suggests that breast cancer mortality can be reduced if resources are applied to the problem in a systematic way. The purpose of the Global Summit Consensus Conference was to begin a process to develop guidelines for improving breast health care in countries with limited resources-those with either low- or medium-level resources based on World Health Organization (WHO) criteria. Breast cancer experts and patient advocates representing 17 countries and 9 world regions participated in the conference. They reviewed the existing breast health guidelines, which generally assume unlimited resources. Individual panels then discussed and debated how limited resources can best be applied to improve three areas of breast health care--early detection, diagnosis, and treatment--and how to integrate these areas in building a breast health care program. The panelists unanimously agreed on the guiding principle that all women have the right to access to health care. They also agreed that collecting data on breast cancer is imperative for deciding how best to apply resources and for measuring progress. The panelists acknowledged the considerable challenges in implementing breast health care programs when resources are limited, as well as the need to build a program that is specific to each country's unique situation. The panelists noted that the development of centralized, specialized cancer centers may be a cost-effective way to deliver breast cancer care to some women when it is not possible to deliver such care to women nationwide. In countries with limited resources, at least half of the women have advanced or metastatic breast cancer at the time of diagnosis. Because advanced breast cancer has the poorest survival rate and is the most resource intensive to treat, measures to reduce the stage at diagnosis are likely to have the greatest overall benefit in terms of both survival and costs. Women should have access to diagnosis and treatment if efforts are undertaken to improve early detection of breast cancer. The panels' findings outline specific steps for prioritizing the use of limited resources to decrease the impact of breast cancer around the globe.

Chung CT, Carlson RW. · Division of Oncology, Stanford University, 300 Pasteur Drive, H0274, Stanford, CA 94305, USA. · Curr Treat Options Oncol. · Pubmed #12594939 No free full text.

Abstract: 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.

Carlson RW. · Department of Medicine, Stanford University, Palo Alto, CA 94304, USA. · Breast Cancer Res Treat. · Pubmed #12353821 No free full text.

Abstract: A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.