Breast Neoplasms: Winer EP

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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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.

Lyman GH, Giuliano AE, Somerfield MR, Benson AB, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP, Anonymous00154. · University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. · J Clin Oncol. · Pubmed #16157938 No free full text.

Abstract: PURPOSE: To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer. METHODS: An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors. RESULTS: The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes. CONCLUSION: SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown.

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.

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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.

Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, Gradishar WJ, Green DM, Langdon RJ, Mitchell RB, Negrin R, Szatrowski TP, Thigpen JT, Von Hoff D, Wasserman TH, Winer EP, Pfister DG. · American Society of Clinical Oncology, Health Services Research Department, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #10506637 No free full text.

Abstract: PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Freedman RA, Winer EP. · No affiliation provided · J Natl Cancer Inst. · Pubmed #19033563 No free full text.

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Lin NU, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #18332468 No free full text.

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Burstein HJ, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #17761968 No free full text.

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Lin NU, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #17563391 No free full text.

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Lin NU, Gelman R, Winer EP. · No affiliation provided · J Natl Cancer Inst. · Pubmed #16333021 links to  free full text

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Krop IE, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #16087947 No free full text.

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Partridge AH, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #15824413 No free full text.

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Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #15755964 No free full text.

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Burstein HJ, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #15738533 No free full text.

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Bunnell CA, Winer EP. · No affiliation provided · J Clin Oncol. · Pubmed #12202656 No free full text.

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Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA. · Indiana University, Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, USA. · Clin Cancer Res. · Pubmed #19088017 No free full text.

Abstract: Triple-negative breast cancer has recently been recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach when compared with other subgroups of breast cancer. Triple-negative breast cancer comprises primarily, but not exclusively, a molecularly distinct subtype of breast cancer, the basal-like subtype. We do not yet have an assay to identify basal-like breast cancer in clinical samples, so triple-negative breast cancer has become a commonly used proxy for this subtype. The molecular biology and pathophysiology of triple-negative breast cancer are not completely understood, but understanding is improving rapidly with the advent of sophisticated molecular biology platforms. Moreover, the established risk factors of breast cancer as a whole may not apply to this unique subgroup of patients. Finally, because triple-negative breast cancer is defined by the absence of a target, there are currently limitations to using a tailored therapeutic approach, leaving conventional cytotoxic therapies as the mainstay. Active preclinical and clinical research programs focus on defining the clinical behavior, delineating the risk factors, and more completely understanding the molecular biology of triple-negative breast cancer to improve prevention, optimize conventional agents, and unveil novel therapeutic targets. This CCR focus article will review the current state of the art on triple-negative breast cancer.

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.

Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, Buzdar AU, Smith IE, Symmans WF, Singh B, Winer EP. · Seattle Cancer Care Alliance, Department of Medicine, 825 Eastlake Ave, EMS G3-200, Seattle, WA 98109-1023, USA. · J Clin Oncol. · Pubmed #18258991 No free full text.

Abstract: PURPOSE: To review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer. METHODS: This article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data. RESULTS: Preoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies. CONCLUSION: In operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology.

Lin NU, Winer EP. · Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Mayer 232, Boston, MA 02115, USA. · J Clin Oncol. · Pubmed #18258989 No free full text.

Abstract: Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

Tolaney SM, Winer EP. · Dana Farber Cancer Institute, 44 Binney Street, Mayer 2, Boston, MA 02115, USA. · Breast. · Pubmed #17697780 No free full text.

Abstract: In the US, over 200,000 new cases of invasive breast cancer are diagnosed each year, with an additional 60,000 cases of ductal carcinoma in situ. The majority of these women will never experience a recurrence of their disease, and most will survive more than 5 years. Follow-up care for these women is focused on addressing long-term complications of therapy, and early detection of new primary cancers and locoregional recurrences. There is no evidence that early detection of distant metastases will lead to an increase in survival, and currently routine imaging studies are not recommended. With the growing number of breast cancer survivors, further studies should be undertaken to study the cost-effectiveness of surveillance strategies.

Punglia RS, Morrow M, Winer EP, Harris JR. · Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. · N Engl J Med. · Pubmed #17554121 No free full text.

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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.

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Lin NU, Winer EP. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. · Clin Cancer Res. · Pubmed #17363517 links to  free full text

Abstract: Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which approximately 20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored.