BREAST CANCER RISK REDUCTION
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1 BREAST CANCER RISK REDUCTION Clinical Practice Guideline Update
2 Introduction ASCO published its first breast cancer risk reduction (BCRR) guideline in 1999 ASCO Guidelines are updated at intervals by an Update Committee of the original Expert Panel BCRR updates published in 2002 and 2009
3 Guideline Methodology: Systematic Review Literature review focused on available systematic reviews and meta-analyses of published phase III randomized controlled trials (RCTs) on breast cancer risk reduction from June 2007 through June 2012 MEDLINE Cochrane Collaboration Library
4 Clinical Questions Which pharmacologic interventions reduce the risk of developing breast cancer in women not previously diagnosed with breast cancer?
5 Recommendations: Tamoxifen Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen (ER)-positive breast cancer, in premenopausal women who are 35 years of age with a 5-year projected absolute BC risk 1.66%, or with LCIS. Risk reduction benefit continues for at least 10 years. Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen (ER)-positive breast cancer, in postmenopausal women who are 35 years of age with a 5- year projected absolute BC risk 1.66%, or with LCIS. Risk reduction benefit continues for at least 10 years.
6 Recommendations: Tamoxifen Is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization. Is not recommended in combination with hormone therapy. Is not recommended for women who are pregnant, women who may become pregnant, or nursing mothers. Follow-up should include a timely work-up of abnormal vaginal bleeding. Discussions with patients and health care providers should include both the risks and benefits of tamoxifen in the preventive setting. DOSAGE: 20 mg/d orally for 5 years.
7 Results from SERM Trials: Tamoxifen vs. placebo NSABP-P1 IBIS-I ITALIAN ROYAL MARSDEN Follow-up (years) 7 (mean 6.2) 10 (median 8.0) 13 (median, 11.2) 20 (median, 13.2) BREAST CANCER INCIDENCE Sample size* TAM PLA All breast cancers TAM PLA RR, 0.73 (0.58 to 0.91) RR, 0.84 (0.60 to 1.17) HR, 0.84 (0.64 to 1.10) Invasive All TAM PLA RR, 0.57 (0.46 to 0.70) RR, 0.74 (0.58 to 0.94) RR, 0.80 (0.56 to 1.15) HR, 0.78 (0.58 to 1.04) ER+ TAM PLA RR, 0.38 (0.28 to 0.50) RR, 0.66 (0.50 to 0.87) RR, 0.77 (0.51 to 1.16) HR, 0.61 (0.43 to 0.86) ER- TAM PLA RR, 1.31 (0.86 to 2.01) RR, 1.00 (0.61 to 1.65) RR, 1.10 (0.59 to 2.05) HR, 1.4 (0.7 to 2.6) Noninvasive All TAM 60 9 PLA 93 6 RR, 0.63 (0.45 to 0.89) RR, 1.50 (0.53 to 4.20) LCIS TAM PLA DCIS TAM PLA 27 9 RR, 0.63 (0.32 to 1.20)
8 Adverse Events/ Side Effects: Tamoxifen vs. placebo NSABP-P1 IBIS-I ITALIAN ROYAL MARSDEN Follow-up (years) 7 (mean 6.2) 10 (median 8.0) 13 (median, 11.2) 20 (median, 13.2) Death TAM PLA RR, 1.10 (0.85 to 1.43) RR, 1.18 (0.81 to 1.73) HR, 0.96 (0.61 to 1.52) HR, 0.99 (0.68 to 1.44) VTE All TAM c PLA c RR, 1.72 (1.27 to 2.36) RR, 1.63 (1.02 to 2.62) DVT TAM PLA RR, 1.44 (0.91 to 2.30) RR, 1.84 (1.21 to 2.82) b PE TAM 28 (see DVT) PLA 13 RR, 2.15 (1.08 to 4.51) Cardiovascular TAM c PLA c RR, 1.03 (0.79 to 1.36) Stroke TAM c PLA c RR, 1.42 (0.97 to 2.08) RR, 1.25 (0.55 to 2.93) RR, 3.11 (0.63 to 15.4) TIA TAM PLA RR, 0.91 (0.54 to 1.52) RR, 0.77 (0.39 to 1.52) RR, 1.24 (0.38 to 4.08)
9 Adverse Events/Side Effects: Tamoxifen vs. placebo NSABP-P1 IBIS-I ITALIAN ROYAL MARSDEN Follow-up (years) 7 (mean 6.2) 10 (median 8.0) 13 (median, 11.2) 20 (median, 13.2) Endometrial TAM c Cancer PLA c RR, 3.28 (1.87 to 6.03) RR, 1.55 (0.68 to 3.65) Fracture TAM c PLA c RR, 0.68 (0.51 to 0.92) RR, 1.02 (0.86 to 1.21) Cataract TAM 67 PLA 54 RR, 1.21 (1.10 to 1.34) RR, 1.24 (0.87 to 1.77) *Sample size included in analyses; a Shen et al, JNCI, 2008; b DVT and PE combined Abbreviations: NSABP-P1, National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial P1; IBIS-I, International Breast Intervention Study; Italian, Italian Randomized Tamoxifen Prevention Trial; Royal Marsden, Royal Marsden Tamoxifen Trial; TAM, tamoxifen; PLA, placebo;, not reported in published literature; NA, not applicable; LCIS, lobular carcinoma in situ; AH, atypical hyperplasia; DCIS, ductal carcinoma in situ; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA, transient ischemic attack; (xx to xx), 95% confidence interval.
10 Recommendations: Raloxifene Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen (ER)-positive breast cancer, in postmenopausal women who are 35 years of age with a 5- year projected absolute BC risk 1.66%, a or with LCIS. May be used longer than 5 years in women with osteoporosis, in whom BC risk reduction is a secondary benefit. Should not be used for BC risk reduction in premenopausal women.
11 Recommendations: Raloxifene Is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack, or during prolonged immobilization. Discussions with patients and health care providers should include both the risks and benefits of raloxifene in the preventive setting. DOSAGE: 60 mg/d orally for 5 years.
12 Follow-up (years) Results from Other SERM Trials CORE MORE RUTH STAR PEARL GENERATIONS 4 + time in MORE trial (median, 7.9) BREAST CANCER INCIDENCE RAL: 5129 Sample size* PLA: 2576 All breast cancers events Invasive All ER+ ER- RAL: 56 PLA: 65 HR, 0.42 (0.29 to 0.60) RAL: 37 PLA: 55 HR, 0.33 (0.21 to 0.49) RAL: 22 PLA: 44 HR, 0.24 (0.15 to 0.40) RAL: 15 PLA: 7 HR, 1.06 (0.43 to 2.59) 4 (median, 3.4) RAL: 5111 PLA: 2571 RAL: RR, 0.38 (0.24 to 0.58) RAL: RR, 0.28 (0.17 to 0.46) RAL: RR, 0.16 (0.09 to 0.30) RAL: 7 (median, 5.6) RAL: 5044 PLA: 5057 RAL: 52 PLA: 76 HR, 0.67 (0.47 to 0.96) RAL: 40 PLA: 70 HR, 0.56 (0.38 to 0.83) RAL: 25 PLA: 55 HR, 0.45 (0.28 to 0.72) RAL:13 PLA: 9 HR, 1.44 (0.61 to 3.36) 8 (median, 6.75) RAL: 9754 TAM: 9736 RAL: TAM: RAL: 310 TAM: 247 RR, 1.24 (1.05 to 1.47) RAL: 109 TAM: 115 RR, 0.94 (0.72 to 1.24) RAL: 51 TAM: 44 RR, 1.15 (0.75 to 1.77) 5 (median, 4.96) LAS (.25mg): 2729 LAS (.5mg): 2745 PLA: 2740 LAS (.25mg): 20 HR, 0.82 (0.45 to 1.49) LAS (.5mg): 5 HR, 0.21 (0.08 to 0.55) PLA: 24 LAS (.25mg):16 HR, 0.79 (0.41 to 1.52) LAS (.5mg): 3 HR, 0.15 (0.04 to 0.50) PLA: 20 LAS (.25mg): 9 HR, 0.50 (0.22 to 1.11) LAS (.5mg): 3 HR, 0.17 (0.05 to 0.57) PLA: 18 LAS (.25mg): 8 HR, 2.55 (0.67 to 9.65) LAS (.5mg): 1 HR, 0.35 (0.04 to 3.34) PLA: 3 4 (median, ) ARZ: 4676 PLA: 4678 ARZ: ARZ: 1% PLA: 2.3% HR, 0.44 (0.26 to 0.76) ARZ: ARZ:
13 Follow-up (years) Results from Other SERM Trials CORE MORE RUTH STAR PEARL GENERATIONS 4 + time in MORE trial (median, 7.9) BREAST CANCER INCIDENCE Noninvasive RAL: 16 All PLA: 7 HR, 1.12 (0.46 to 2.73) LCIS DCIS RAL: RAL: 4 (median, 3.4) RAL: RAL: RAL: 7 (median, 5.6) RAL: RAL: RAL: 8 (median, 6.75) RAL: 137 TAM: 111 RR, 1.22 (0.95 to 1.59) RAL: 34 TAM: 33 RR, 1.02 (0.61 to 1.70) RAL: 86 TAM: 70 RR, 1.22 (0.88 to 1.69) 5 (median, 4.96) LAS (.25mg): LAS (.5mg): LAS (.25mg): LAS (.5mg): LAS (.25mg): 4 HR, 1.00 (0.25 to 3.99) LAS (.5mg): 2 HR, 0.50 (0.09 to 2.73) PLA: 4 4 (median, ) ARZ: ARZ: ARZ:
14 ADVERSE EVENTS/SIDE EFFECTS Death RAL: 47 PLA: 29 P=.27 VTE Endometrial Cancer All RAL: 47 PLA: 13 P=.094 DVT PE RAL: 31 PLA: 10 P=.32 RAL: 17 PLA: 2 P=.05 RAL: 7 PLA: 4 P=.75 Adverse Events/Side Effects: Other SERM Trials CORE MORE RUTH STAR PEARL GENERATIONS RAL: HR, 0.61 (0.36 to 1.03) RAL: RAL: P=.002 RAL: HR, 3.97 (0.91 to 17.3) RAL: HR, 0.69 (0.22 to 2.18) RAL: 554 PLA: 595 HR, 0.92 (0.82 to 1.03) RAL: 103 PLA: 71 HR, 1.44 (1.06 to 1.95) RAL: 65 PLA: 47 HR, 1.37 (0.94 to 1.99) RAL: 36 PLA: 24 HR, 1.49 (0.89 to 2.49) RAL: 21 PLA: 27 P=.53 RAL: 202 TAM: 236 RR, 0.84 (0.70 to 1.02) RAL: 154 TAM: 202 RR, 0.75 (0.60 to 0.93) RAL: 86 TAM: 118 RR, 0.72 (0.54 to 0.95) RAL: 68 TAM: 84 RR,.080 (0.57 to 1.11) RAL: 37 TAM: 65 RR, 0.55 (0.36 to 0.83) LAS (.25mg): 90 HR, 1.38 (1.00 to 1.89) LAS (.5mg): 73 HR, 1.12 (0.80 to 1.56) PLA: 65 LAS (.25mg): 48 HR, 2.67 (1.55 to 4.58) LAS (.5mg): 37 HR, 2.06 (1.17 to 3.61) PLA: 18 LAS (.25mg): LAS (.5mg): LAS (.25mg): 12 HR, 5.98 (1.34 to 26.7) LAS (.5mg): 9 HR, 4.49; 0.97 to 20.8 PLA: 2 LAS (.25mg): 3 LAS (.5mg): 2 PLA: 3 ARZ: 105 PLA: 98 P=.62 ARZ: 63 PLA: 27 P<.001 ARZ: 26 PLA: 9 P=.004 ARZ: 16 PLA: 7 P=.06 ARZ: 9 PLA: 4 P=.16
15 Adverse Events/Side Effects: Other SERM Trials CORE MORE RUTH STAR PEARL GENERATIONS ADVERSE EVENTS/SIDE EFFECTS Cardiovascular Stroke TIA RAL: RAL: RAL: RAL: RAL: HR, 0.68 (0.43 to 1.07) RAL: RAL: RAL: HR, 1.10 (0.92 to 1.32) RAL: RAL: 126 TAM: 114 RR, 1.10 (0.85 to 1.43) RAL: 51 TAM: 53 RR, 0.96 (0.64 to 1.43) RAL: 50 TAM: 41 RR, 1.21 (0.79 to 1.88) LAS (.25mg): 73 HR, 0.76 (0.56 to 1.03) LAS (.5mg): 65 HR, 0.68 (0.50 to 0.93) PLA: 95 LAS (.25mg): 31 HR, 0.61 (0.39 to 0.96) LAS (.5mg): 32 HR, 0.64 (0.41 to 0.99) PLA: 50 LAS (.25mg): 19 HR, 1.35 (0.68 to 2.69) LAS (.5mg): 14 HR, 1.00 (0.48 to 2.09) PLA:14 ARZ: 116 PLA: 113 P=.88 ARZ: 47 PLA: 42 P=.59 ARZ:
16 ADVERSE EVENTS/SIDE EFFECTS Fracture RAL: Cataract P<.05 RAL: Adverse Events/Side Effects: Other SERM Trials CORE MORE RUTH STAR PEARL GENERATIONS RAL: 64 PLA: 97 RR, 0.66 (0.55 to 0.81) RAL: RAL: V 64; NV 428 PLA: V 97; NV 438 V: HR, 0.65 (0.47 to 0.89); NV: HR, 0.96 (0.84 to 1.10) RAL: 374 PLA: 391 P=.56 RAL: 96 TAM: 104 RR, 0.92 (0.69 to 1.22) RAL: 603 TAM: 739 RR, 0.80 (0.72 to 0.89) LAS (.25mg): V: 189/2734 HR, 0.69 (0.57 to 0.83) NV: 269/2852 HR, 0.90 (0.76 to 1.06) LAS (.5mg): V: 156/2748 HR, 0.58 (0.47 to 0.70) NV: 230/2852 HR, 0.76 (0.64 to 0.91) PLA: V: 262/2744 (HR, ) NV: 296/2852 (HR, ) LAS (.25mg): LAS (.5mg): ARZ: V: 109/4192 NV: 334/4192 PLA: V: 179/4162 NV: 354/4162 V: RR, 0.61 (0.48 to 0.77); NV: RR, 0.94 (0.81 to 1.10) ARZ: Abbreviations: TAM, tamoxifen; RAL, raloxifene; PLA, placebo; LAS, lasofoxifene; ARZ, arzoxifene;, not reported in published literature; V, vertebral fractures; NV, nonvertebral fractures; (xx to xx), 95% confidence interval; CORE, Continuing Outcomes Relevant to Evista; MORE, Multiple Outcomes of Raloxifene Evaluation; RUTH, Raloxifene Use for the Heart; STAR, National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial P2; PEARL, Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene; GENERATIONS, Generations Trial; LCIS, lobular carcinoma in situ; AH, atypical hyperplasia; DCIS, ductal carcinoma in situ; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA, transient ischemic attack.
17 Recommendations: Exemestane Should be discussed as an alternative to tamoxifen and/or raloxifene to reduce the risk of invasive breast cancer, specifically estrogen (ER)-positive breast cancer, in postmenopausal women who are 35 years of age with a 5- year projected absolute BC risk 1.66%, or with LCIS or atypical hyperplasia. Should not be used for BC risk reduction in premenopausal women. Discussions with patients and health care providers should include both the risks and benefits of exemestane in the preventive setting. DOSAGE: 25 mg/d orally for 5 years.
18 Results from Aromatase Inhibitor Trials: Follow-up (years) BREAST CANCER INCIDENCE Sample size* All breast cancers Invasive Noninvasive All MAP.3 3 (median): range 0 to 63.4 months EXE:2285, PLA:2275 EXE: 20 PLA: 44 HR, 0.47 (0.27 to 0.79 ) EXE: 11, PLA: 32 HR, 0.35 (0.18 to 0.70) ER+ EXE: 7 PLA: 27 HR, 0.27 (0.12 to 0.60) ER- EXE: 4 PLA: 5 HR, 0.80 (0.21 to 2.98) All LCIS EXE: 4 PLA: 11 HR, 0.36 (0.11 to 1.12) b DCIS EXE: 9 PLA: 14 HR, 0.65 (0.28 to 1.51)
19 Results from Aromatase Inhibitor Trials: MAP.3 Follow-up (years) 3 (median): range 0 to 63.4 months ADVERSE EVENTS/SIDE EFFECTS Sample Size EXE: 2240 PLA: 2248 Death EXE: 19 PLA: 19 VTE EXE: 11 All PLA: 7 DVT PE Cardiovascular EXE: 106 PLA: 111 P=.78 Stroke EXE: 13 PLA: 11 TIA (see stroke) Endometrial Cancer EXE: 5 PLA: 8 Fracture EXE: 149 PLA: 143 P=.72 Cataract *Sample size included in analyses; a Only results from cognitive subprotocol available (Jenkins et al, Lancet Oncol, 2008). Abbreviations: EXE, exemestane; ANA, anastrozole; PLA, placebo;, not reported in published literature; IBIS-II, International Breast Intervention Study (II) ; LCIS, lobular carcinoma in situ; AH, atypical hyperplasia; DCIS, ductal carcinoma in situ; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA, transient ischemic attack. b Results for incidence of atypical ductal hyperplasia, atypical lobular hyperplasia, and LCIS combined
20 Patient and Clinician Communication Key Discussion Points Assessment and discussion of individual risk of developing breast cancer Options for reducing the risk of developing breast cancer (nonpharmacologic and pharmacologic) Potential impact of specific chemoprevention agents on the incidence of both invasive and noninvasive breast cancers Potential risks and side effects of chemoprevention agents
21 Patient and Clinician Communication Key Discussion Points Long-term effectiveness of the chemoprevention agents Chemoprevention studies were not powered to detect differences in mortality as it was considered that a reduction in incidence was itself an important clinical endpoint. Accessibility - cost/insurance coverage Resources/materials for consideration (e.g. Plan for follow-up.
22 Health Disparities Challenges to minimizing health disparities include: Equal access to health care Racially diverse participation in clinical trials Improved risk assessment models Racial, ethnic, and socioeconomic status may affect health outcomes and/or create barriers to access and use of chemoprevention agents for BCRR In addition to age and comorbidities, race is important when considering risk-benefit profiles, so race-specific estimates should be considered and incorporated in discussions between patients and clinicians
23 Need for: Future Directions Research to address poor uptake of BCRR in high-risk women Effective tools and approaches to educate providers on chemoprevention Efficacious interventions that communicate to eligible women the risks and benefits of specific chemoprevention agents Tools that more accurately identify women at increased risk Greater understanding of what disparities and barriers exist with regard to chemoprevention use among high-risk women
24 Intervention The Bottom Line Pharmacologic interventions for breast cancer risk reduction, including selective estrogen receptor modulators and aromatase inhibitors Target Audience Medical Oncologists, Surgical Oncologists, Gynecologists, Primary Care Physicians, General Practitioners Key Recommendations Tamoxifen (20 mg/d orally for 5 years) should be discussed as an option to reduce the risk of invasive breast cancer, specifically estrogen (ER)-positive breast cancer, in premenopausal or postmenopausal women 35 years of age at increased risk of breast cancer, or with lobular carcinoma in situ (LCIS). Tamoxifen is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, during prolonged immobilization, in women who are pregnant or who may become pregnant, or nursing mothers. Tamoxifen is not recommended in combination with hormone therapy.
25 Key Recommendations The Bottom Line Raloxifene (60 mg/d orally for 5 years) should be discussed as an option to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in postmenopausal women 35 years of age at increased risk of breast cancer, or with LCIS. It should not be used for breast cancer risk reduction in premenopausal women. Raloxifene is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization. Exemestane (25 mg/d orally for 5 years) should be discussed as an alternative to tamoxifen or raloxifene to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in postmenopausal women 35 years of age at increased risk of breast cancer, or with LCIS or atypical hyperplasia. Exemestane should not be used for breast cancer risk reduction in premenopausal women. For tamoxifen and raloxifene, the most favorable risk-benefit profile is seen in women at greatest risk of developing breast cancer.
26 Key Recommendations (con t) The Bottom Line Discussions with patients and health care providers should include both the risks and benefits of each agent under consideration. NOTE1: Refer to Table 1 for the complete recommendations. NOTE2: Increased risk is defined as a 5 year projected absolute risk of breast cancer 1.66% on the NCI Breast Cancer Risk Assessment Tool or an equivalent measure. NOTE3: Trials were not designed to assess mortality and the impact of the agent on overall survival or breast cancer-specific survival has not been demonstrated in 10 years of follow-up. Methods A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the 2009 ASCO clinical practice guideline recommendations needed to be updated.
27 Additional Resources A Data Supplement and clinical tools and resources can be found on ASCO s Web site at: Patient information is also available at:
28 Update Committee Panel Members UPDATE COMMITTEE MEMBER Kala Visvanathan, MD, MHS, Co- Chair Scott M. Lippman, MD, Co-Chair Elissa Bantug, MHS Powel Brown, MD, PhD Nananda Col, MD, MPH Jack Cuzick, PhD Nancy E. Davidson, MD Andrea De Censi, MD Carol Fabian, MD AFFILIATION Johns Hopkins Medical Institutions, Baltimore, MD Moores Cancer Center, University of California, San Diego, CA Johns Hopkins Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD MD Anderson Cancer Center, University of Texas, Houston, TX University of New England, Biddeford, ME Queen Mary University of London, UK University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, PA E.O. Ospedali Galliera, Italy University of Kansas Medical Center, Kansas City, KS
29 Update Committee Panel Members UPDATE COMMITTEE MEMBER Leslie Ford, MD Judy Garber, MD, MPH Maria Katapodi, PhD, RN, FAAN Barnett Kramer, MD, MPH Monica Morrow, MD Barbara Parker, MD Carolyn Runowicz, MD Victor Vogel III, MD James L. Wade, MD AFFILIATION National Cancer Institute, Bethesda, MD Dana Farber Cancer Institute, Boston, MA University of Michigan School of Nursing, Ann Arbor, MI National Cancer Institute, Bethesda, MD Memorial Sloan Kettering Cancer Center, New York, NY Moores Cancer Center, University of California, San Diego, CA Herbert Wertheim College of Medicine, Florida International University, Miami, FL Geisinger Medical Center Cancer Institute, Danville, PA Cancer Care Specialists of Central Illinois, Decatur, IL
30 ASCO Guidelines The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. ( ASCO ) to assist practitioners in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action.
31 ASCO Guidelines [Cont d] The use of words like must, must not, should, and should not indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating physician in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an as is basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.
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