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Hormone Blocking: Endocrine Therapy
Lauren Q. Chang Sen, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Clinical Issues

        TERMINOLOGY

        • Definitions

          • Endocrine therapy (ET) for ER(+) breast cancer: ↓ estrogen production or blocks its effects
            • Tamoxifen (TAM): Blocks estrogen effects; adjuvant therapy for ER(+) breast cancer in men and pre- and postmenopausal women to ↓ recurrence; also used in prevention (women)
            • Aromatase inhibitors (AI): Block estrogen production; adjuvant therapy for ER(+) breast cancer in postmenopausal women to ↓ recurrence
              • Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin)
          • Ovarian suppression agents: Gonadotropin-releasing hormone agonists, luteinizing hormone-releasing hormone
          • Risk-reducing therapy
            • TAM: High-risk pre-/postmenopausal women
            • Raloxifene: Only in postmenopausal women

        IMAGING

        • Mammographic Findings

          • MR Findings

            • Nuclear Medicine Findings

              PATHOLOGY

              • General Features

                CLINICAL ISSUES

                • Treatment

                  • Risks

                    Selected References

                    1. Francis PA et al: Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 379(2):122-37, 2018
                    2. Costa M et al: Risk reduction strategies in breast cancer prevention. Eur J Breast Health. 13(3):103-12, 2017
                    3. Engmann NJ et al: Longitudinal changes in volumetric breast density with tamoxifen and aromatase inhibitors. Cancer Epidemiol Biomarkers Prev. 26(6):930-7, 2017
                    4. Lee CI et al: Fulvestrant for hormone-sensitive metastatic breast cancer. Cochrane Database Syst Rev. 1:CD011093, 2017
                    5. Shawky MS et al: Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies. Oncotarget. 8(3):5578-91, 2017
                    6. Burstein HJ et al: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression summary. J Oncol Pract. 12(4):390-3, 2016
                    7. Ekpo EU et al: Relationship between breast density and selective estrogen-receptor modulators, aromatase inhibitors, physical activity, and diet: a systematic review. Integr Cancer Ther. 15(2):127-44, 2016
                    8. Mullooly M et al: Mammographic density as a biosensor of tamoxifen effectiveness in adjuvant endocrine treatment of breast cancer: opportunities and implications. J Clin Oncol. 34(18):2093-7, 2016
                    9. Nyante SJ et al: Longitudinal change in mammographic density among ER-positive breast cancer patients using tamoxifen. Cancer Epidemiol Biomarkers Prev. 25(1):212-6, 2016
                    10. Rugo HS et al: Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 34(25):3069-103, 2016
                    11. Spring LM et al: Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2(11):1477-86, 2016
                    12. Cuzick J et al: Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 16(1):67-75, 2015
                    13. Early Breast Cancer Trialists' Collaborative Group (EBCTCG).: aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 386(10001):1341-52, 2015
                    14. Nyante SJ et al: Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst. 107(3), 2015
                    15. Burstein HJ et al: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 32(21):2255-69, 2014
                    16. Giess CS et al: Background parenchymal enhancement at breast MR imaging: normal patterns, diagnostic challenges, and potential for false-positive and false-negative interpretation. Radiographics. 34(1):234-47, 2014
                    17. Schrading S et al: Effects of tamoxifen and aromatase inhibitors on breast tissue enhancement in dynamic contrast-enhanced breast MR imaging: a longitudinal intraindividual cohort study. Radiology. 271(1):45-55, 2014
                    18. Davies C et al: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 381(9869):805-16, 2013
                    19. Ko KL et al: Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. Breast Cancer Res Treat. 142(3):559-67, 2013
                    20. Li J et al: Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol. 31(18):2249-56, 2013
                    21. Nelson HD et al: Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 158(8):604-14, 2013
                    22. Kim J et al: Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res. 14(4):R102, 2012
                    23. King V et al. Effect of aromatase inhibitors on background parenchymal enhancement and amount of fibroglandular tissue at breast MR imaging. Radiology. 264(3):670-8, 2012
                    24. King V et al: Impact of tamoxifen on amount of fibroglandular tissue, background parenchymal enhancement, and cysts on breast magnetic resonance imaging. Breast J. 18(6):527-34, 2012
                    25. Smith J et al: A pilot study of letrozole for one year in women at enhanced risk of developing breast cancer: effects on mammographic density. Anticancer Res. 32(4):1327-31, 2012
                    26. Amir E et al: Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 103(17):1299-309, 2011
                    27. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) et al: Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 378(9793):771-84, 2011
                    28. Goss PE et al: 3 study investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. Epub 2011 Jun 4. Erratum in: N Engl J Med. 365(14):1361, 2011
                    29. Regan MM et al: Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 12(12):1101-8, 2011
                    30. Burstein HJ et al: Adjuvant hormonal therapy for early-stage breast cancer. Surg Oncol Clin N Am. 19(3):639-47, 2010
                    31. Chia YH et al: Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. Br J Cancer. 103(6):759-64, 2010
                    32. Cuzick J et al: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11(12):1135-41, 2010
                    33. Pearman L et al: The effects of raloxifene on mammographic breast density: a review of clinical trials. Menopause. 17(3):654-9, 2010
                    34. Vogel VG et al: Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila). 3(6):696-706, 2010
                    35. Arimidex et al: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9(1):45-53, 2008
                    36. Eng-Wong J et al: Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 17(7):1696-701, 2008
                    37. Coates AS et al: Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 25(5):486-92, 2007
                    38. Coombes RC et al: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. Erratum in: Lancet. 369(9565):906, 2007
                    39. Mauri D et al: Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst. 98(18):1285-91, 2006
                    40. Vogel VG et al: Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. JAMA. 295:2727-41, 2006
                    41. Early Breast Cancer Trialists' Collaborative Group: effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 365:1687-717, 2005
                    42. Howell A et al: Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 104(2):236-9, 2005
                    43. Cuzick J et al: Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 96(8):621-8, 2004
                    44. Martino S et al: Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 96(23):1751-61, 2004
                    45. Mouridsen H et al: Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 21(11):2101-9, 2003
                    46. Osborne CK et al: Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 20(16):3386-95, 2002
                    47. Cauley JA et al: Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat. 65(2):125-34, 2001
                    48. Cummings SR et al: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 281(23):2189-97, 1999
                    49. Tamoxifen for early breast cancer: an overview of the randomised trials: Early Breast Cancer Trialists' Collaborative Group. Lancet. 351(9114):1451-67, 1998
                    50. Fisher B et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 90:1371-1388, 1998
                    Related Anatomy
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                    Related Differential Diagnoses
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                    References
                    Tables

                    Tables

                    KEY FACTS

                    • Terminology

                      • Imaging

                        • Clinical Issues

                          TERMINOLOGY

                          • Definitions

                            • Endocrine therapy (ET) for ER(+) breast cancer: ↓ estrogen production or blocks its effects
                              • Tamoxifen (TAM): Blocks estrogen effects; adjuvant therapy for ER(+) breast cancer in men and pre- and postmenopausal women to ↓ recurrence; also used in prevention (women)
                              • Aromatase inhibitors (AI): Block estrogen production; adjuvant therapy for ER(+) breast cancer in postmenopausal women to ↓ recurrence
                                • Anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin)
                            • Ovarian suppression agents: Gonadotropin-releasing hormone agonists, luteinizing hormone-releasing hormone
                            • Risk-reducing therapy
                              • TAM: High-risk pre-/postmenopausal women
                              • Raloxifene: Only in postmenopausal women

                          IMAGING

                          • Mammographic Findings

                            • MR Findings

                              • Nuclear Medicine Findings

                                PATHOLOGY

                                • General Features

                                  CLINICAL ISSUES

                                  • Treatment

                                    • Risks

                                      Selected References

                                      1. Francis PA et al: Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 379(2):122-37, 2018
                                      2. Costa M et al: Risk reduction strategies in breast cancer prevention. Eur J Breast Health. 13(3):103-12, 2017
                                      3. Engmann NJ et al: Longitudinal changes in volumetric breast density with tamoxifen and aromatase inhibitors. Cancer Epidemiol Biomarkers Prev. 26(6):930-7, 2017
                                      4. Lee CI et al: Fulvestrant for hormone-sensitive metastatic breast cancer. Cochrane Database Syst Rev. 1:CD011093, 2017
                                      5. Shawky MS et al: Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies. Oncotarget. 8(3):5578-91, 2017
                                      6. Burstein HJ et al: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression summary. J Oncol Pract. 12(4):390-3, 2016
                                      7. Ekpo EU et al: Relationship between breast density and selective estrogen-receptor modulators, aromatase inhibitors, physical activity, and diet: a systematic review. Integr Cancer Ther. 15(2):127-44, 2016
                                      8. Mullooly M et al: Mammographic density as a biosensor of tamoxifen effectiveness in adjuvant endocrine treatment of breast cancer: opportunities and implications. J Clin Oncol. 34(18):2093-7, 2016
                                      9. Nyante SJ et al: Longitudinal change in mammographic density among ER-positive breast cancer patients using tamoxifen. Cancer Epidemiol Biomarkers Prev. 25(1):212-6, 2016
                                      10. Rugo HS et al: Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 34(25):3069-103, 2016
                                      11. Spring LM et al: Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2(11):1477-86, 2016
                                      12. Cuzick J et al: Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 16(1):67-75, 2015
                                      13. Early Breast Cancer Trialists' Collaborative Group (EBCTCG).: aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 386(10001):1341-52, 2015
                                      14. Nyante SJ et al: Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst. 107(3), 2015
                                      15. Burstein HJ et al: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 32(21):2255-69, 2014
                                      16. Giess CS et al: Background parenchymal enhancement at breast MR imaging: normal patterns, diagnostic challenges, and potential for false-positive and false-negative interpretation. Radiographics. 34(1):234-47, 2014
                                      17. Schrading S et al: Effects of tamoxifen and aromatase inhibitors on breast tissue enhancement in dynamic contrast-enhanced breast MR imaging: a longitudinal intraindividual cohort study. Radiology. 271(1):45-55, 2014
                                      18. Davies C et al: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 381(9869):805-16, 2013
                                      19. Ko KL et al: Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. Breast Cancer Res Treat. 142(3):559-67, 2013
                                      20. Li J et al: Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol. 31(18):2249-56, 2013
                                      21. Nelson HD et al: Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 158(8):604-14, 2013
                                      22. Kim J et al: Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res. 14(4):R102, 2012
                                      23. King V et al. Effect of aromatase inhibitors on background parenchymal enhancement and amount of fibroglandular tissue at breast MR imaging. Radiology. 264(3):670-8, 2012
                                      24. King V et al: Impact of tamoxifen on amount of fibroglandular tissue, background parenchymal enhancement, and cysts on breast magnetic resonance imaging. Breast J. 18(6):527-34, 2012
                                      25. Smith J et al: A pilot study of letrozole for one year in women at enhanced risk of developing breast cancer: effects on mammographic density. Anticancer Res. 32(4):1327-31, 2012
                                      26. Amir E et al: Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 103(17):1299-309, 2011
                                      27. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) et al: Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 378(9793):771-84, 2011
                                      28. Goss PE et al: 3 study investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. Epub 2011 Jun 4. Erratum in: N Engl J Med. 365(14):1361, 2011
                                      29. Regan MM et al: Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 12(12):1101-8, 2011
                                      30. Burstein HJ et al: Adjuvant hormonal therapy for early-stage breast cancer. Surg Oncol Clin N Am. 19(3):639-47, 2010
                                      31. Chia YH et al: Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. Br J Cancer. 103(6):759-64, 2010
                                      32. Cuzick J et al: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11(12):1135-41, 2010
                                      33. Pearman L et al: The effects of raloxifene on mammographic breast density: a review of clinical trials. Menopause. 17(3):654-9, 2010
                                      34. Vogel VG et al: Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila). 3(6):696-706, 2010
                                      35. Arimidex et al: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9(1):45-53, 2008
                                      36. Eng-Wong J et al: Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 17(7):1696-701, 2008
                                      37. Coates AS et al: Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 25(5):486-92, 2007
                                      38. Coombes RC et al: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. Erratum in: Lancet. 369(9565):906, 2007
                                      39. Mauri D et al: Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst. 98(18):1285-91, 2006
                                      40. Vogel VG et al: Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. JAMA. 295:2727-41, 2006
                                      41. Early Breast Cancer Trialists' Collaborative Group: effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 365:1687-717, 2005
                                      42. Howell A et al: Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 104(2):236-9, 2005
                                      43. Cuzick J et al: Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 96(8):621-8, 2004
                                      44. Martino S et al: Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 96(23):1751-61, 2004
                                      45. Mouridsen H et al: Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 21(11):2101-9, 2003
                                      46. Osborne CK et al: Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 20(16):3386-95, 2002
                                      47. Cauley JA et al: Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat. 65(2):125-34, 2001
                                      48. Cummings SR et al: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 281(23):2189-97, 1999
                                      49. Tamoxifen for early breast cancer: an overview of the randomised trials: Early Breast Cancer Trialists' Collaborative Group. Lancet. 351(9114):1451-67, 1998
                                      50. Fisher B et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 90:1371-1388, 1998