BREAST CANCER RISK REDUCTION Clinical Practice Guideline Update www.asco.org/guidelines/www.asco.org/guidelines/ © American Society of Clinical Oncology®.

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BREAST CANCER RISK REDUCTION Clinical Practice Guideline Update © American Society of Clinical Oncology®. All rights reserved.

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 © American Society of Clinical Oncology®. All rights reserved.

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 © American Society of Clinical Oncology®. All rights reserved.

Clinical Questions Which pharmacologic interventions reduce the risk of developing breast cancer in women not previously diagnosed with breast cancer? © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

Results from SERM Trials: Tamoxifen vs. placebo © American Society of Clinical Oncology®. All rights reserved. NSABP-P1IBIS-IITALIANROYAL 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 NR PLA NR NRRR, 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 60NR9 PLA 93NR6 RR, 0.63 (0.45 to 0.89)NRRR, 1.50 (0.53 to 4.20)NR LCIS TAM NR PLA NR DCIS TAM NR17NR14 PLA NR27NR9 RR, 0.63 (0.32 to 1.20)NR

Adverse Events/ Side Effects: Tamoxifen vs. placebo © American Society of Clinical Oncology®. All rights reserved. NSABP-P1IBIS-IITALIANROYAL 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 NR117448c8c PLA NR68283c3c NRRR, 1.72 (1.27 to 2.36)RR, 1.63 (1.02 to 2.62)NR DVT TAM 4968NR PLA 3437NR RR, 1.44 (0.91 to 2.30)RR, 1.84 (1.21 to 2.82) b NR PE TAM 28 (see DVT) NR PLA 13NR RR, 2.15 (1.08 to 4.51)NR Cardiovascular TAM 113NR 10 c PLA 109NR 12 c RR, 1.03 (0.79 to 1.36)NR Stroke TAM c7c PLA c9c RR, 1.42 (0.97 to 2.08)RR, 1.25 (0.55 to 2.93)RR, 3.11 (0.63 to 15.4)NR TIA TAM 31176NR PLA 34225NR RR, 0.91 (0.54 to 1.52)RR, 0.77 (0.39 to 1.52)RR, 1.24 (0.38 to 4.08)NR

Adverse Events/Side Effects: Tamoxifen vs. placebo *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; NR, 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. © American Society of Clinical Oncology®. All rights reserved. NSABP-P1IBIS-IITALIANROYAL MARSDEN Follow-up (years)7 (mean 6.2)10 (median 8.0)13 (median, 11.2)20 (median, 13.2) Endometrial Cancer TAM 5317NR13 c PLA 1711NR5c5c RR, 3.28 (1.87 to 6.03)RR, 1.55 (0.68 to 3.65)NR Fracture TAM NR19 c PLA 80235NR22 c RR, 0.68 (0.51 to 0.92)RR, 1.02 (0.86 to 1.21)NR Cataract TAM NR67NR PLA NR54NR RR, 1.21 (1.10 to 1.34)RR, 1.24 (0.87 to 1.77)NR

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. © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

Results from Other SERM Trials COREMORERUTHSTARPEARLGENERATIONS Follow-up (years) 4 + time in MORE trial (median, 7.9) 4 (median, 3.4) 7 (median, 5.6) 8 (median, 6.75) 5 (median, 4.96) 4 (median, NR) BREAST CANCER INCIDENCE Sample size* RAL: 5129 PLA: 2576 RAL: 5111 PLA: 2571 RAL: 5044 PLA: 5057 RAL: 9754 TAM: 9736 LAS (.25mg): 2729 LAS (.5mg): 2745 PLA: 2740 ARZ: 4676 PLA: 4678 All breast cancers events RAL: 56 PLA: 65 HR, 0.42 (0.29 to 0.60) RAL: NR PLA: NR RR, 0.38 (0.24 to 0.58) RAL: 52 PLA: 76 HR, 0.67 (0.47 to 0.96) RAL: NR TAM: NR NR LAS (.25mg): 20 HR, 0.82 (0.45 to 1.49) LAS (.5mg): 5 HR, 0.21 (0.08 to 0.55) PLA: 24 ARZ: NR PLA: NR NR Invasive All RAL: 37 PLA: 55 HR, 0.33 (0.21 to 0.49) RAL: NR PLA: NR RR, 0.28 (0.17 to 0.46) RAL: 40 PLA: 70 HR, 0.56 (0.38 to 0.83) RAL: 310 TAM: 247 RR, 1.24 (1.05 to 1.47) LAS (.25mg):16 HR, 0.79 (0.41 to 1.52) LAS (.5mg): 3 HR, 0.15 (0.04 to 0.50) PLA: 20 ARZ: 1% PLA: 2.3% HR, 0.44 (0.26 to 0.76) ER+ RAL: 22 PLA: 44 HR, 0.24 (0.15 to 0.40) RAL: NR PLA: NR RR, 0.16 (0.09 to 0.30) RAL: 25 PLA: 55 HR, 0.45 (0.28 to 0.72) RAL: 109 TAM: 115 RR, 0.94 (0.72 to 1.24) LAS (.25mg): 9 HR, 0.50 (0.22 to 1.11) LAS (.5mg): 3 HR, 0.17 (0.05 to 0.57) PLA: 18 ARZ: NR PLA: NR NR ER- RAL: 15 PLA: 7 HR, 1.06 (0.43 to 2.59) RAL: NR PLA: NR NR RAL:13 PLA: 9 HR, 1.44 (0.61 to 3.36) RAL: 51 TAM: 44 RR, 1.15 (0.75 to 1.77) LAS (.25mg): 8 HR, 2.55 (0.67 to 9.65) LAS (.5mg): 1 HR, 0.35 (0.04 to 3.34) PLA: 3 ARZ: NR PLA: NR NR © American Society of Clinical Oncology®. All rights reserved.

Results from Other SERM Trials COREMORERUTHSTARPEARLGENERATIONS Follow-up (years) 4 + time in MORE trial (median, 7.9) 4 (median, 3.4) 7 (median, 5.6) 8 (median, 6.75) 5 (median, 4.96) 4 (median, NR) BREAST CANCER INCIDENCE Noninvasive All RAL: 16 PLA: 7 HR, 1.12 (0.46 to 2.73) RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: 137 TAM: 111 RR, 1.22 (0.95 to 1.59) LAS (.25mg): NR LAS (.5mg): NR PLA: NR ARZ: NR PLA: NR NR LCIS RAL: NR PLA: NR NR RAL:NR PLA: NR NR RAL: NR PLA: NR NR RAL: 34 TAM: 33 RR, 1.02 (0.61 to 1.70) LAS (.25mg): NR LAS (.5mg): NR PLA: NR ARZ: NR PLA: NR NR DCIS RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: 86 TAM: 70 RR, 1.22 (0.88 to 1.69) LAS (.25mg): 4 HR, 1.00 (0.25 to 3.99) LAS (.5mg): 2 HR, 0.50 (0.09 to 2.73) PLA: 4 ARZ: NR PLA: NR NR © American Society of Clinical Oncology®. All rights reserved.

Adverse Events/Side Effects: Other SERM Trials COREMORERUTHSTARPEARLGENERATIONS ADVERSE EVENTS/SIDE EFFECTS Death RAL: 47 PLA: 29 P=.27 RAL: NR PLA: NR HR, 0.61 (0.36 to 1.03) RAL: 554 PLA: 595 HR, 0.92 (0.82 to 1.03) RAL: 202 TAM: 236 RR, 0.84 (0.70 to 1.02) LAS (.25mg): 90 HR, 1.38 (1.00 to 1.89) LAS (.5mg): 73 HR, 1.12 (0.80 to 1.56) PLA: 65 ARZ: 105 PLA: 98 P=.62 VTE All RAL: 47 PLA: 13 P=.094 RAL: NR PLA: NR NR RAL: 103 PLA: 71 HR, 1.44 (1.06 to 1.95) RAL: 154 TAM: 202 RR, 0.75 (0.60 to 0.93) LAS (.25mg): 48 HR, 2.67 (1.55 to 4.58) LAS (.5mg): 37 HR, 2.06 (1.17 to 3.61) PLA: 18 ARZ: 63 PLA: 27 P<.001 DVT RAL: 31 PLA: 10 P=.32 RAL: NR PLA: NR P=.002 RAL: 65 PLA: 47 HR, 1.37 (0.94 to 1.99) RAL: 86 TAM: 118 RR, 0.72 (0.54 to 0.95) LAS (.25mg): NR LAS (.5mg): NR PLA: NR NR ARZ: 26 PLA: 9 P=.004 PE RAL: 17 PLA: 2 P=.05 RAL: NR PLA: NR HR, 3.97 (0.91 to 17.3) RAL: 36 PLA: 24 HR, 1.49 (0.89 to 2.49) RAL: 68 TAM: 84 RR,.080 (0.57 to 1.11) LAS (.25mg): 12 HR, 5.98 (1.34 to 26.7) LAS (.5mg): 9 HR, 4.49; 0.97 to 20.8 PLA: 2 ARZ: 16 PLA: 7 P=.06 Endometrial Cancer RAL: 7 PLA: 4 P=.75 RAL: NR PLA: NR HR, 0.69 (0.22 to 2.18) RAL: 21 PLA: 27 P=.53 RAL: 37 TAM: 65 RR, 0.55 (0.36 to 0.83) LAS (.25mg): 3 LAS (.5mg): 2 PLA: 3 NR ARZ: 9 PLA: 4 P=.16 © American Society of Clinical Oncology®. All rights reserved.

Adverse Events/Side Effects: Other SERM Trials COREMORERUTHSTARPEARLGENERATIONS ADVERSE EVENTS/SIDE EFFECTS Cardiovascular RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: 126 TAM: 114 RR, 1.10 (0.85 to 1.43) LAS (.25mg): 73 HR, 0.76 (0.56 to 1.03) LAS (.5mg): 65 HR, 0.68 (0.50 to 0.93) PLA: 95 ARZ: 116 PLA: 113 P=.88 Stroke RAL: NR PLA: NR NR RAL: NR PLA: NR HR, 0.68 (0.43 to 1.07) RAL: NR PLA: NR HR, 1.10 (0.92 to 1.32) RAL: 51 TAM: 53 RR, 0.96 (0.64 to 1.43) LAS (.25mg): 31 HR, 0.61 (0.39 to 0.96) LAS (.5mg): 32 HR, 0.64 (0.41 to 0.99) PLA: 50 ARZ: 47 PLA: 42 P=.59 TIA RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: 50 TAM: 41 RR, 1.21 (0.79 to 1.88) 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: NR PLA: NR NR © American Society of Clinical Oncology®. All rights reserved.

Adverse Events/Side Effects: Other SERM Trials COREMORERUTHSTARPEARLGENERATIONS ADVERSE EVENTS/SIDE EFFECTS Fracture RAL: NR PLA: NR P<.05 RAL: 64 PLA: 97 RR, 0.66 (0.55 to 0.81) 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: 96 TAM: 104 RR, 0.92 (0.69 to 1.22) 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, NR) NV: 296/2852 (HR, NR) 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) Cataract RAL: NR PLA: NR NR RAL: NR PLA: NR NR RAL: 374 PLA: 391 P=.56 RAL: 603 TAM: 739 RR, 0.80 (0.72 to 0.89) LAS (.25mg): NR LAS (.5mg): NR PLA: NR NR ARZ: NR PLA: NR NR Abbreviations: TAM, tamoxifen; RAL, raloxifene; PLA, placebo; LAS, lasofoxifene; ARZ, arzoxifene; NR, 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. © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

Results from Aromatase Inhibitor Trials: MAP.3 Follow-up (years)3 (median): range 0 to 63.4 months BREAST CANCER INCIDENCE Sample size*EXE:2285, PLA:2275 All breast cancers EXE: 20 PLA: 44 HR, 0.47 (0.27 to 0.79 ) Invasive All 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) Noninvasive All NR 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) © American Society of Clinical Oncology®. All rights reserved.

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 NR VTE All EXE: 11 PLA: 7 NR DVTNR PENR Cardiovascular EXE: 106 PLA: 111 P=.78 Stroke EXE: 13 PLA: 11 NR TIA(see stroke) Endometrial Cancer EXE: 5 PLA: 8 NR Fracture EXE: 149 PLA: 143 P=.72 CataractNR *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; NR, 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 © American Society of Clinical Oncology®. All rights reserved.

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 (non- pharmacologic 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 © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

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 © American Society of Clinical Oncology®. All rights reserved.

Future Directions Need for: 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 © American Society of Clinical Oncology®. All rights reserved.

The Bottom Line Intervention 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. © American Society of Clinical Oncology®. All rights reserved.

The Bottom Line Key Recommendations 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. © American Society of Clinical Oncology®. All rights reserved.

The Bottom Line Key Recommendations (con’t) 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. © American Society of Clinical Oncology®. All rights reserved.

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: know-ascos-guidelines/what-know-ascos-guideline-drugs- lower-breast-cancer-risk know-ascos-guidelines/what-know-ascos-guideline-drugs- lower-breast-cancer-risk © American Society of Clinical Oncology®. All rights reserved.

Update Committee Panel Members UPDATE COMMITTEE MEMBERAFFILIATION Kala Visvanathan, MD, MHS, Co- Chair Johns Hopkins Medical Institutions, Baltimore, MD Scott M. Lippman, MD, Co-Chair Moores Cancer Center, University of California, San Diego, CA Elissa Bantug, MHSJohns Hopkins Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD Powel Brown, MD, PhDMD Anderson Cancer Center, University of Texas, Houston, TX Nananda Col, MD, MPHUniversity of New England, Biddeford, ME Jack Cuzick, PhDQueen Mary University of London, UK Nancy E. Davidson, MDUniversity of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, PA Andrea De Censi, MDE.O. Ospedali Galliera, Italy Carol Fabian, MDUniversity of Kansas Medical Center, Kansas City, KS © American Society of Clinical Oncology®. All rights reserved.

Update Committee Panel Members UPDATE COMMITTEE MEMBERAFFILIATION Leslie Ford, MD National Cancer Institute, Bethesda, MD Judy Garber, MD, MPHDana Farber Cancer Institute, Boston, MA Maria Katapodi, PhD, RN, FAANUniversity of Michigan School of Nursing, Ann Arbor, MI Barnett Kramer, MD, MPHNational Cancer Institute, Bethesda, MD Monica Morrow, MDMemorial Sloan Kettering Cancer Center, New York, NY Barbara Parker, MD Moores Cancer Center, University of California, San Diego, CA Carolyn Runowicz, MDHerbert Wertheim College of Medicine, Florida International University, Miami, FL Victor Vogel III, MDGeisinger Medical Center Cancer Institute, Danville, PA James L. Wade, MDCancer Care Specialists of Central Illinois, Decatur, IL © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.

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. © American Society of Clinical Oncology®. All rights reserved.