Advertisement

Endocrine Treatment of Young Patients with EBC

  • Olivia PaganiEmail author
Chapter
  • 62 Downloads

Abstract

Breast cancer in young women is a complex disease, still surrounded by many misconceptions and taboos. Hormone receptor-positive (HR+) disease is less frequent in this age group compared to older women but anyhow represents about 60% of cases. In developed countries, the majority of young women with HR+ breast cancer have early disease at diagnosis. The optimal endocrine therapy in this setting has been debated for decades: long-term survival with modern therapies has dramatically improved over the years, making individualization of treatment the everyday challenge for healthcare professionals.

The present review summarizes the most recent guidelines and discusses in particular the available treatment options in patients at different risk of recurrence, considering also the toxicity profiles which impact adherence and ultimately outcomes.

The future challenges and research priorities will also be briefly discussed.

Keywords

Young women Endocrine therapy Tamoxifen Ovarian function suppression Aromatase inhibitors Side effects 

References

  1. 1.
    Azim HA Jr, et al. Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res. 2012;18(5):1341–51.PubMedCrossRefGoogle Scholar
  2. 2.
    Keegan TH, et al. Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res. 2012;14(2):R55.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Swain SM, et al. Quantitative gene expression by recurrence score in ER-positive breast Cancer, by age. Adv Ther. 2015;32(12):1222–36.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Chollet-Hinton L, et al. Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina breast cancer study: a case-control study. Breast Cancer Res. 2016;18(1):79.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Partridge AH, et al. Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34(27):3308–14.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Sestak I, Cuzick J. Markers for the identification of late breast cancer recurrence. Breast Cancer Res. 2015;17:10.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Paik S, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Sparano JA, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Cardoso F, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717–29.CrossRefGoogle Scholar
  10. 10.
    Paluch-Shimon S, et al. ESO-ESMO 3rd international consensus guidelines for breast cancer in young women (BCY3). Breast. 2017;35:203–17.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    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. 2011;378(9793):771–84.CrossRefGoogle Scholar
  12. 12.
    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. J Clin Oncol. 2016;34(14):1689–701.PubMedCrossRefGoogle Scholar
  13. 13.
    Curigliano G, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast Cancer 2017. Ann Oncol. 2017;28(8):1700–12.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Senkus E, et al. Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Dowsett M, et al. The biology of steroid hormones and endocrine treatment of breast cancer. Breast. 2005;14(6):452–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Francis PA, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–46.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Pagani O, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–18.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Regan MM, et al. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013;22(6):1094–100.PubMedCrossRefGoogle Scholar
  19. 19.
    Regan MM, et al. Absolute benefit of adjuvant endocrine therapies for premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast Cancer: TEXT and SOFT trials. J Clin Oncol. 2016;34(19):2221–31.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Zhou Q, et al. Prognostic impact of chemotherapy-induced amenorrhea on premenopausal breast cancer: a meta-analysis of the literature. Menopause. 2015;22(10):1091–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Francis PA, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122–37.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Tevaarwerk AJ, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the eastern cooperative oncology group. J Clin Oncol. 2014;32(35):3948–58.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Sparano JA, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast Cancer. N Engl J Med. 2018;379(2):111–21.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Francis PA. Adjuvant endocrine therapy for premenopausal women: type and duration. Breast. 2017;34(Suppl 1):S108–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Rossi L, Pagani O. The role of gonadotropin-releasing-hormone analogues in the treatment of breast Cancer. J Women’s Health (Larchmt). 2018;27(4):466–75.CrossRefGoogle Scholar
  26. 26.
    Pagani O, Regan MM, Francis PA. Are SOFT and TEXT results practice changing and how? Breast. 2016;27:122–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Lamerato L, et al. Breast cancer recurrence and related mortality in U.S. pts with early breast cancer. J Clin Oncol. 2005;23(Suppl 16):738.CrossRefGoogle Scholar
  28. 28.
    Le MG, et al. Prognostic factors for death after an isolated local recurrence in patients with early-stage breast carcinoma. Cancer. 2002;94(11):2813–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Sorensen SV, et al. Incidence-based cost-of-illness model for metastatic breast cancer in the United States. Int J Technol Assess Health Care. 2012;28(1):12–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Gnant M, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian breast and colorectal Cancer study group trial 12. Ann Oncol. 2015;26(2):313–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Saha P, et al. Treatment efficacy, adherence, and quality of life among women younger than 35 years in the international breast Cancer study group TEXT and SOFT adjuvant endocrine therapy trials. J Clin Oncol. 2017;35(27):3113–22.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Regan MM, et al. Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT. Ann Oncol. 2017;28(9):2225–32.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Lambertini M, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data. J Clin Oncol. 2018;36(19):1981–90.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Pfeiler G, et al. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011;29(19):2653–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Jatoi I, et al. Breast cancer adjuvant therapy: time to consider its time-dependent effects. J Clin Oncol. 2011;29(17):2301–4.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Yu KD, et al. Hazard of breast cancer-specific mortality among women with estrogen receptor-positive breast cancer after five years from diagnosis: implication for extended endocrine therapy. J Clin Endocrinol Metab. 2012;97(12):E2201–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Wimmer K, et al. Optimal duration of adjuvant endocrine therapy: how to apply the newest data. Ther Adv Med Oncol. 2017;9(11):679–92.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    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. 2013;381(9869):805–16.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Goss PE, et al. Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole. Ann Oncol. 2013;24(2):355–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Ruddy KJ, et al. Extended therapy with letrozole and ovarian suppression in premenopausal patients with breast cancer after tamoxifen. Clin Breast Cancer. 2014;14(6):413–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Noh WC, et al. Role of adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: the ASTRRA study. J Clin Oncol. 2018;36(Suppl 15):502.CrossRefGoogle Scholar
  42. 42.
    Runowicz CD, et al. American Cancer Society/American Society of Clinical Oncology breast Cancer survivorship care guideline. J Clin Oncol. 2016;34(6):611–35.PubMedCrossRefGoogle Scholar
  43. 43.
    Rosenberg SM, et al. Symptoms and symptom attribution among women on endocrine therapy for breast Cancer. Oncologist. 2015;20(6):598–604.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Takeuchi EE, et al. Impact of patient-reported outcomes in oncology: a longitudinal analysis of patient-physician communication. J Clin Oncol. 2011;29(21):2910–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Chen J, Ou L, Hollis SJ. A systematic review of the impact of routine collection of patient reported outcome measures on patients, providers and health organisations in an oncologic setting. BMC Health Serv Res. 2013;13:211.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Absolom K, et al. Electronic patient self-reporting of adverse-events: patient information and aDvice (eRAPID): a randomised controlled trial in systemic cancer treatment. BMC Cancer. 2017;17(1):318.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Holch P, et al. Development of an integrated electronic platform for patient self-report and management of adverse events during cancer treatment. Ann Oncol. 2017;28(9):2305–11.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Henry, NL. Endocrine therapy toxicity: management options. Am Soc Clin Oncol Educ Book. 2014:e25–30.Google Scholar
  49. 49.
    Sverrisdottir A, et al. Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy. J Clin Oncol. 2004;22(18):3694–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Vehmanen L, et al. Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol. 2006;24(4):675–80.PubMedCrossRefGoogle Scholar
  51. 51.
    Rossi L, Pagani O. The modern landscape of endocrine therapy for premenopausal women with breast Cancer. Breast Care (Basel). 2015;10(5):312–5.CrossRefGoogle Scholar
  52. 52.
    Chien AJ, et al. Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer. Breast Cancer Res Treat. 2015;153(1):173–81.PubMedCrossRefGoogle Scholar
  53. 53.
    Braems G, et al. Use of tamoxifen before and during pregnancy. Oncologist. 2011;16(11):1547–51.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Christinat A, Di Lascio S, Pagani O. Hormonal therapies in young breast cancer patients: when, what and for how long? J Thorac Dis. 2013;5(Suppl 1):S36–46.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Paganini-Hill A, Clark LJ. Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2000;64(2):165–76.PubMedCrossRefGoogle Scholar
  56. 56.
    Schilder CM, et al. Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol. 2010;28(8):1294–300.PubMedCrossRefGoogle Scholar
  57. 57.
    Nystedt M, et al. Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study. J Clin Oncol. 2003;21(9):1836–44.PubMedCrossRefGoogle Scholar
  58. 58.
    Phillips KA, et al. Adjuvant ovarian function suppression and cognitive function in women with breast cancer. Br J Cancer. 2016;114(9):956–64.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Underwood EA, et al. Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis. Breast Cancer Res Treat. 2018;168(2):299–310.PubMedCrossRefGoogle Scholar
  60. 60.
    Kelly CM, Pritchard KI. CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal women: lessons learned. J Natl Cancer Inst. 2012;104(6):427–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Sacco K, Grech G. Actionable pharmacogenetic markers for prediction and prognosis in breast cancer. EPMA J. 2015;6(1):15.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Ribi K, et al. Adjuvant Tamoxifen plus ovarian function suppression versus Tamoxifen alone in premenopausal women with early breast Cancer: patient-reported outcomes in the suppression of ovarian function trial. J Clin Oncol. 2016;34(14):1601–10.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Hurny C, et al. The Perceived Adjustment to Chronic Illness Scale (PACIS): a global indicator of coping for operable breast cancer patients in clinical trials. Swiss Group for Clinical Cancer Research (SAKK) and the International Breast Cancer Study Group (IBCSG). Support Care Cancer. 1993;1(4):200–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Dowsett M, Folkerd E. Deficits in plasma oestradiol measurement in studies and management of breast cancer. Breast Cancer Res. 2005;7(1):1–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Bellet M, et al. Twelve-month estrogen levels in premenopausal women with hormone receptor-positive breast Cancer receiving adjuvant Triptorelin plus Exemestane or Tamoxifen in the suppression of ovarian function trial (SOFT): the SOFT-EST substudy. J Clin Oncol. 2016;34(14):1584–93.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Masuda N, et al. Monthly versus 3-monthly goserelin acetate treatment in pre-menopausal patients with estrogen receptor-positive early breast cancer. Breast Cancer Res Treat. 2011;126(2):443–51.PubMedCrossRefGoogle Scholar
  67. 67.
    Bernhard J, et al. Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. Lancet Oncol. 2015;16(7):848–58.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Artigalas O, et al. Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis. BMC Med. 2015;13:139.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Johansson H, et al. Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial. Breast Cancer Res. 2016;18(1):110.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Pagani O, et al. Impact of SERM adherence on treatment effect: international breast Cancer study group trials 13-93 and 14-93. Breast Cancer Res Treat. 2013;142(2):455–9.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Hershman DL, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529–37.PubMedCrossRefGoogle Scholar
  72. 72.
    Murphy CC, et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459–78.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Llarena NC, et al. Impact of fertility concerns on Tamoxifen initiation and persistence. J Natl Cancer Inst. 2015;107(10):djv202.PubMedCentralCrossRefGoogle Scholar
  74. 74.
    Cluze C, et al. Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time. Ann Oncol. 2012;23(4):882–90.PubMedCrossRefGoogle Scholar
  75. 75.
    Brufsky AM, Dickler MN. Estrogen receptor-positive breast Cancer: exploiting signaling pathways implicated in endocrine resistance. Oncologist. 2018;23:528.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Institute of Oncology of Southern SwitzerlandGeneva University Hospitals, Swiss Group for Clinical Cancer Research (SAKK), and International Breast Cancer Study Group (IBCSG)Lugano, ViganelloSwitzerland

Personalised recommendations