Breast Neoplasms: Chlebowski RT

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.

Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, Cauley JA, Blumenstein BA, Albain KS, Lipton A, Brown S, Anonymous00022. · No affiliation provided · J Clin Oncol. · Pubmed #12963702 No free full text.

Abstract: PURPOSE: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women. RESULTS: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates. In patients with a serum creatinine less than 3.0 mg/dL (265 mumol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. Creatinine should be monitored before each dose of either agent in accordance with US Food and Drug Administration (FDA) labeling. Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of the osteoporosis risk in women with breast cancer. The panel recommends an algorithm for patient management to maintain bone health. CONCLUSION: Bisphosphonates provide a supportive, albeit expensive and non-life-prolonging, benefit to many patients with bone metastases. Current research is focusing on bisphosphonates as adjuvant therapy. Although new data addressing when to stop therapy, alternative doses or schedules for administration, and how to best coordinate bisphosphonates with other palliative therapies are needed, they are not currently being investigated.

Hillner BE, Ingle JN, Berenson JR, Janjan NA, Albain KS, Lipton A, Yee G, Biermann JS, Chlebowski RT, Pfister DG. · American Society of Clinical Oncology, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #10715310 No free full text.

Abstract: PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. METHODS: An expert multidisciplinary panel reviewed pertinent information from the published literature and meeting abstracts through May 1999. Additional data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed, and investigators were contacted for more recent information. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus was used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implications. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Research Committee, and the ASCO Board of Directors. RESULTS: Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercalcemia. Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. For women with only an abnormal bone scan but without bony destruction by imaging studies or localized pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsistent results. Starting bisphosphonates in patients at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in premenopausal patients with treatment-induced menopause. The panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The panel stresses that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femur require careful evaluation for spinal cord compression and pathologic fracture before bisphosphonate use and if symptoms recur, persist, or worsen during therapy. The panel recommends that current standards of care for cancer pain, analgesics and local radiation therapy, not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, since it was associated with a modest pain control benefit in controlled trials. CONCLUSION: Bisphosphonates provide a meaningful supportive but not life-prolonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metastases, to identify their role in the adjuvant setting in preventing bone metastases, and to better determine their cost-benefit consequences.

Chlebowski RT. · No affiliation provided · Womens Health (Lond Engl). · Pubmed #19072509 No free full text.

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Chlebowski RT, Prentice RL. · No affiliation provided · J Natl Cancer Inst. · Pubmed #18812547 No free full text.

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Chlebowski RT, Anderson GL. · No affiliation provided · J Natl Cancer Inst. · Pubmed #15812065 links to  free full text

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Chlebowski RT. · No affiliation provided · J Clin Oncol. · Pubmed #15684314 No free full text.

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Chlebowski RT, McTiernan A. · No affiliation provided · J Natl Cancer Inst. · Pubmed #12509389 links to  free full text

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Col NF, Chlebowski RT. · Center for Outcomes Research and Evaluation, Maine Medical Center, Portland, ME 04101, USA. · Menopause. · Pubmed #18596602 No free full text.

Abstract: Decision making about menopausal therapies is complex because of the number of clinical factors that must be considered. Menopausal hormone therapy can relieve the vasomotor symptoms of menopause, but the most common preparation, combination estrogen and progesterone, increases the risk of breast cancer. Both tamoxifen and raloxifene can reduce the risk of developing invasive breast cancer, but the adverse effects of these drugs differ substantially. Risk models have been built to identify women at high risk for developing breast cancer, but their application in clinical practice has been develop disappointingly low. We propose an approach for identifying and managing menopausal women at high risk for breast cancer that can be readily implemented in clinical practice. The first step is to identify women at sufficiently high risk for breast cancer to merit treatment. For women aged 45 or older, the presence of one or more first-degree relatives with breast cancer and one or more previous breast biopsies will identify those whose 5-year risk is 2% or higher. For women 55 years or older, the presence of either one of these risk factors is sufficient. Any woman with a family history of breast cancer should be assessed as to whether she is likely to carry a BRCA mutation and referred for genetic counseling and possible genetic testing. Decisions about treatment options should be based on the presence or absence of bothersome vasomotor symptoms, an intact uterus, and risk factors for cardiovascular disease. A simple algorithm is presented to streamline identification and management of menopausal women at high risk for breast cancer.

Miaskowski C, Shockney L, Chlebowski RT. · Department of Physiological Nursing, University of California, San Francisco, CA, USA. · Clin J Oncol Nurs. · Pubmed #18390458 links to  free full text

Abstract: Many factors contribute to the success or failure of adjuvant therapy, but perhaps one of the most critical is treatment adherence. Patients do not adhere to prescribed therapy for a variety of reasons, and each one should be uncovered and addressed or managed accordingly to maintain therapeutic levels and give patients the best chance for positive outcomes. Nurses are well positioned to play a central role in promoting adherence by ensuring that patients understand the need for treatment and by identifying any underlying causes of nonadherence to therapy. When the issues are identified and addressed effectively, patients' chances for successful clinical outcomes are greatly improved. This article summarizes the issues surrounding adherence, paying specific attention to adjuvant endocrine therapy for breast cancer, and outlines strategies to reduce nonadherence that nurses can incorporate into clinical practice.

Chlebowski RT. · Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Building J-3, Torrance, CA 90502, USA. · Breast. · Pubmed #18367397 No free full text.

Abstract: Tamoxifen has been the standard first-line adjuvant treatment for postmenopausal women with early breast cancer for over 3 decades. Its use, however, is associated with a number of potentially life-threatening adverse events. As a result, the aromatase inhibitors (AIs), which are generally better tolerated and more efficacious, are now beginning to supersede tamoxifen as the treatment of choice in this setting. Nevertheless, some patients in clinical practice still start or remain on tamoxifen therapy instead of an AI. This review investigates our current understanding of AIs and tamoxifen in the adjuvant hormonal therapy of postmenopausal breast cancer in relation to efficacy, safety and patient benefits. Overall, it is concluded that the AIs show a significant advantage over tamoxifen, with the greatest difference observed at 1-2 years after initiation of treatment. Therefore, using an AI at the earliest opportunity provides patients with the best option to prevent the recurrence and excess adverse events associated with tamoxifen.

Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J, Anonymous00119. · Department of Internal Medicine/Endocrinology, University of Virginia Health System, Box 801416, Charlottesville, Virginia 22908, USA. · Endocr Relat Cancer. · Pubmed #17639036 links to  free full text

Abstract: The majority of candidates for breast cancer prevention have not accepted tamoxifen because of the perception of an unfavorable risk/benefit ratio and the acceptance of raloxifene remains to be determined. One means of improving this ratio is to identify women at very high risk of breast cancer. Family history, age, atypia in a benign biopsy, and reproductive factors are the main parameters currently used to determine risk. The most powerful risk factor, mammographic density, is not presently employed routinely. Other potentially important factors are plasma estrogen and androgen levels, bone density, weight gain, age of menopause, and fracture history, which are also not currently used in a comprehensive risk prediction model because of lack of prospective validation. The Breast Cancer Prevention Collaborative Group (BCPCG) met to critically examine and prioritize risk factors that might be selected for further testing by multivariate analysis using existing clinical material. The BCPCG reached a consensus that quantitative breast density, state of the art plasma estrogen and androgen measurements, history of fracture and height loss, BMI, and waist-hip ratio had sufficient priority for further testing. As a practical approach, these parameters could be added to the existing Tyrer-Cuzick model which encompasses factors included in both the Claus and Gail models. The BCPCG analyzed potentially available clinical material from previous prospective studies and determined that a large case/control study to evaluate these new factors might be feasible at this time.

Chlebowski RT, Geller ML. · Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502-2064, USA. · Oncology. · Pubmed #17344666 No free full text.

Abstract: PURPOSE: Despite the demonstrated efficacy of long-duration adjuvant tamoxifen and aromatase inhibitor use in breast cancer management, information on adherence to such therapy is limited. Therefore, we reviewed the published literature regarding hormonal therapy adherence in clinical trial and practice settings. METHODS: A systematic search of the PubMed database, augmented by a review of manuscript references and conference proceedings, commonly identified adherence reports in clinical trials but identified only 9 adherence reports in clinical practice settings. RESULTS: In adjuvant breast cancer clinical trials with longer (> or =4 years) follow-up, hormonal therapy (tamoxifen or aromatase inhibitors) was prematurely discontinued by about 23-28% of the study participants. Adherence to aromatase inhibitors did not differ from adherence to tamoxifen in this setting. In breast cancer prevention trials, tamoxifen was prematurely discontinued by 20-46% of the participants. In clinical practice settings, only 2 reports addressed longer-duration (>4 years) adherence to adjuvant tamoxifen use. In these, tamoxifen was prematurely discontinued by 30-50% of the patients. CONCLUSION: Adherence to prescribed breast cancer hormone therapy has not received concerted attention. Current, albeit limited, evidence suggests long-term hormone therapy adherence may represent an area limiting optimal breast cancer patient treatment.

Chlebowski RT, Anderson GL, Geller M, Col N. · Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA 90502-2004, USA. · Clin Breast Cancer. · Pubmed #16595028 No free full text.

Abstract: Results from the Women's Health Initiative randomized clinical trials of hormone therapy provide the clinical context for interpreting tamoxifen and aromatase inhibitor (AI) findings regarding coronary heart disease (CHD) and stroke. Of note is the potential link between increased stroke risk and increased dementia risk seen with the use of estrogen alone and the combination of estrogen/progestin. Like hormone therapy, tamoxifen has been found to generally lower low-density lipoprotein and total cholesterol but increase triglyceride levels. The preponderance of clinical evidence suggests that tamoxifen increases stroke risk and has no effect or modestly reduces CHD risk. Aromatase inhibitors generally do not influence low-density lipoprotein cholesterol and could modestly increase high-density lipoprotein cholesterol and reduce triglyceride levels. Current but limited evidence suggests that AIs have a modest increase or no effect on CHD as a class or as individual agents compared with tamoxifen. The influence of AIs on stroke is unsettled, and within-class differences might exist. In the adjuvant breast cancer setting, based on available evidence, the influence of AIs on CHD or stroke will infrequently influence overall patient outcome. If remaining issues are to be addressed, more rigorous CHD and stroke assessment procedures are needed in future trials evaluating AIs.

Chlebowski RT. · Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, 1124 W Carson St, Building J-3, Torrance, CA 90502, USA. · Clin Breast Cancer. · Pubmed #15807922 No free full text.

Abstract: Bone health is an increasingly important concern in breast cancer survivors because in postmenopausal women, bone-sparing tamoxifen is being replaced by aromatase inhibitors, whereas in premenopausal women, ovarian suppression is playing an increasing role in adjuvant management. Estrogen reduction resulting from aromatase inhibition and ovarian suppression are associated with loss in bone mineral density (BMD) and an increase in fracture risk. These side effects must be placed in context of the overall risks and benefits seen with these interventions. The American Society of Clinical Oncology has outlined a management strategy for bone health maintenance in breast cancer survivors with early-stage disease that incorporates baseline and ongoing screening for BMD and treatment based on BMD results. Limited but consistent data suggest bisphosphonate therapy represents a treatment option for this condition. A variety of interventions to maintain bone health in breast cancer survivors are undergoing clinical evaluation and include the oral bisphosphonates risedronate and clodronate, the intravenous bisphosphonate zoledronic acid, the receptor activator of nuclear factor-kB ligand inhibitor AMG-162, and the hormonal agent tibolone. Current information suggests bone loss associated with estrogen reduction in breast cancer survivors may represent a preventable and treatable condition. Ongoing clinical trials will definitively evaluate this hypothesis.

Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR. · Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115, USA. · J Clin Oncol. · Pubmed #15545664 No free full text.

Abstract: PURPOSE: To update the 2003 American Society of Clinical Oncology technology assessment on adjuvant use of aromatase inhibitors. RECOMMENDATIONS: Based on results from multiple large randomized trials, adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence. Neither the optimal timing nor duration of aromatase inhibitor therapy is established. Aromatase inhibitors are appropriate as initial treatment for women with contraindications to tamoxifen. For all other postmenopausal women, treatment options include 5 years of aromatase inhibitors treatment or sequential therapy consisting of tamoxifen (for either 2 to 3 years or 5 years) followed by aromatase inhibitors for 2 to 3, or 5 years. Patients intolerant of aromatase inhibitors should receive tamoxifen. There are no data on the use of tamoxifen after an aromatase inhibitor in the adjuvant setting. Women with hormone receptor-negative tumors should not receive adjuvant endocrine therapy. The role of other biomarkers such as progesterone receptor and HER2 status in selecting optimal endocrine therapy remains controversial. Aromatase inhibitors are contraindicated in premenopausal women; there are limited data concerning their role in women with treatment-related amenorrhea. The side effect profiles of tamoxifen and aromatase inhibitors differ. The late consequences of aromatase inhibitor therapy, including osteoporosis, are not well characterized. CONCLUSION: The Panel believes that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen. Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options.

Chlebowski RT, Kim JA, Col NF. · Harbor-UCLA Research and Education Institute, Torrance 90502, USA. · Semin Oncol. · Pubmed #14663778 No free full text.

Abstract: Vasomotor symptoms associated with menopause or cancer therapies represent an increasingly common problem for breast cancer survivors given the increasing use of ovarian suppression in premenopausal women and aromatase inhibitors in postmenopausal women. Although estrogen and/or progestin effectively reduce vasomotor symptoms, a recent Women's Health Initiative (WHI) randomized trial identified an unfavorable risk/benefit balance on life-threatening diseases, including increased breast cancer, for combined estrogen plus progestin use in otherwise healthy postmenopausal women. As a result, use of menopausal hormone therapy (MHT) for chronic disease risk reduction in any population cannot be supported. In addition, the safety of estrogen and/or progestin regarding risk of recurrence or new cancer development in breast cancer survivors has not been demonstrated. For vasomotor symptoms in this population, neuroendocrine agents, including selective seratonin reuptake inhibitors (SSRIs) or gabapentin, are reasonable choices with substantial impact on hot flashes and moderate toxicity profiles. When rigorously evaluated, most other nonhormonal pharmacologic and herbal interventions have been found to have either modest or no efficacy and/or limiting toxicity. In breast cancer survivors even local vulvar/vaginal symptoms are best treated by nonhormone products since drug absorption with systemic estrogen-like effects has been reported. Estrogen/progestin use in breast cancer survivors should be considered only for women with severe vasomotor symptoms refractory to other approaches after extensive informed decision-making including review of current Food and Drug Administration labeling concerns with use limited to the lowest dose and shortest duration possible.

Geller ML, Chlebowski RT. · Harbor-UCLA Research and Education Institute, Torrance, CA 90502, USA. · Fertil Steril. · Pubmed #14568281 No free full text.

Abstract: Two large recent studies indicate an increased risk of breast cancer with use of menopausal hormone therapy (HT), particularly combinations of estrogen and progestogen. These studies also go against previous theories of the types of breast cancer that would be associated with HT use. Emerging information regarding the influence of estrogen plus progestin on breast cancer risk adds further weight to the recommendation against use for chronic disease risk reduction and raises additional questions regarding risks of even short-term use for vasomotor symptoms associated with menopause.

Chlebowski RT, Col N, Winer EP, Collyar DE, Cummings SR, Vogel VG, Burstein HJ, Eisen A, Lipkus I, Pfister DG, Anonymous00100. · Health Services Research Department, American Society of Clinical Oncology, 1900 Duke Street, Suite 200, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #12149307 No free full text.

Abstract: OBJECTIVE: To update an evidence-based technology assessment of chemoprevention strategies for breast cancer risk reduction. POTENTIAL INTERVENTIONS: Tamoxifen, raloxifene, aromatase inhibition, and fenretinide. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO) prescribed technology assessment procedure was followed. VALUES: More weight was given to published randomized trials. BENEFITS/HARMS: A woman's decision regarding breast cancer risk reduction strategies is complex and will depend on the importance and weight attributed to information regarding both cancer- and noncancer-related risks and benefits. CONCLUSIONS: For women with a defined 5-year projected breast cancer risk of > or= 1.66%, tamoxifen (at 20 mg/d for 5 years) may be offered to reduce their risk. Risk/benefit models suggest that greatest clinical benefit with least side effects is derived from use of tamoxifen in younger (premenopausal) women (who are less likely to have thromboembolic sequelae and uterine cancer), women without a uterus, and women at higher breast cancer risk. Data do not as yet suggest that tamoxifen provides an overall health benefit or increases survival. In all circumstances, tamoxifen use should be discussed as part of an informed decision-making process with careful consideration of individually calculated risks and benefits. Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting. This technology assessment represents an ongoing process and recommendations will be updated in a timely matter. VALIDATION: The conclusions were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Winer EP, Hudis C, Burstein HJ, Chlebowski RT, Ingle JN, Edge SB, Mamounas EP, Gralow J, Goldstein LJ, Pritchard KI, Braun S, Cobleigh MA, Langer AS, Perotti J, Powles TJ, Whelan TJ, Browman GP. · Health Services Research Department, American Society of Clinical Oncology, 1900 Duke Street, Suite 200, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #12149306 No free full text.

Abstract: OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)-prescribed technology assessment procedure was followed. BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician's decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non-cancer-related risks and benefits. CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A 5-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor-positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.) VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Vargas HI, Romero L, Chlebowski RT. · Department of Surgery, Division of Surgical Oncology, Harbor-UCLA Medical Center, 1000 W. Carson Street, Box 25, Torrance, CA 90502, USA. · Curr Treat Options Oncol. · Pubmed #12057078 No free full text.

Abstract: Bloody nipple discharge causes a high degree of anxiety in women because of fear of breast cancer. Commonly, the absence of palpable or mammographic abnormalities gives a false sense of security, causing delays in diagnosis. Initial evaluation with physical examination and mammography is useful in detecting high-risk cases. Bloody nipple discharge is most frequently benign. It is caused by intraductal papilloma, duct ectasia, and less frequently by breast cancer. Several diagnostic tests have been proposed to establish the cause of bloody nipple discharge. Galactography, ultrasound, and exfoliative cytology are useful only when positive, but have a high rate of false-negative results and do not preclude histologic diagnosis. More recently, ductal lavages in combination with cytology have provided promising results, but experience and long-term follow-up are limited. Traditional treatment is surgical excision of the involved ductal system from which the discharge emanates. Ductal excision has been the only reliable procedure in establishing a certain diagnosis and in controlling the bloody discharge. The early success reported with image-guided excision of papilloma and duct endoscopy promises a significant improvement in our diagnostic accuracy from minimally invasive emerging technology.

Chlebowski RT, Aiello E, McTiernan A. · Harbor-University of California Los Angeles Research and Education Institute, Torrance, CA 90502, USA. · J Clin Oncol. · Pubmed #11844838 No free full text.

Abstract: PURPOSE: To systematically review and summarize evidence relevant to obesity and breast cancer clinical outcome, potential hormonal mediating mechanisms, and the current status of weight loss interventions for chronic disease management. METHODS: A comprehensive, formal literature review was conducted to identify 5,687 citations with key information from 159 references summarized in text and tables. This process included a search for all breast cancer studies exploring associations among survival or recurrence and obesity at diagnosis or weight gain after diagnosis using prospective criteria. RESULTS: On the basis of observational studies, women with breast cancer who are overweight or gain weight after diagnosis are found to be at greater risk for breast cancer recurrence and death compared with lighter women. Obesity is also associated with hormonal profiles likely to stimulate breast cancer growth. Recently, use of weight loss algorithms proven successful in other clinical settings that incorporate dietary therapy, physical activity, and ongoing behavior therapy have been endorsed by the National Institutes of Health and other health agencies. CONCLUSION: Although definitive weight loss intervention trials in breast cancer patients remain to be conducted, the current evidence relating increased body weight to adverse breast cancer outcome and the documented favorable effects of weight loss on clinical outcome in other comorbid conditions support consideration of programs for weight loss in breast cancer patients. Recommendations for the clinical care of overweight or obese breast cancer patients are offered.

Chlebowski RT. · Harbor-UCLA Research and Education Institute, 1124 W. Carson Street, Torrance, California 90502-2064, USA. · Annu Rev Med. · Pubmed #11818488 No free full text.

Abstract: Breast cancer risk reduction now represents an achievable medical objective. Current interventions include selective estrogen receptor modulators (SERMs), prophylactic surgery, and lifestyle change. For SERMs, current evidence supports tamoxifen use for breast cancer risk reduction whereas raloxifene requires further study. Prophylactic mastectomy and prophylactic oophorectomy, effective in retrospective clinical experiences, should be considered only for women at substantial risk willing to accept the irreversible consequences of these procedures. Although dietary fat intake is under clinical trial evaluation, lifestyle change, including weight loss, dietary change, and increased physical activity, can be recommended based on other health considerations. Use of any intervention requires careful breast cancer risk assessment, risk-benefit calculations, and informed decision making with full patient participation. Future breast cancer risk assessment may incorporate additional biologic measures of estrogen exposure and/or analyses of collected breast cells. Under active evaluation are novel SERMs, aromatase inhibitors/inactivators, gonadotrophin-releasing hormone agonists, retinoids, statins, and tyrosine kinase and cyclooxygenase-2 inhibitors.

Chlebowski RT. · Harbor-UCLA Research and Education Institute, Torrance, CA, USA. · Semin Oncol. · Pubmed #11544575 No free full text.

Abstract: Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.

Chlebowski RT. · Harbor-UCLA Research and Education Institute, Torrance, Calif 90502, USA. · N Engl J Med. · Pubmed #10900280 No free full text.

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