Skip to main content
SpringerLink
Log in

Pharmacotherapeutic Management of Breast Cancer in Elderly Patients: The Promise of Novel Agents

Drugs & Aging Aims and scope Submit manuscript

Abstract

As its incidence increases with age, breast cancer in elderly patients takes on a growing importance in clinical oncology practice. Management decisions are challenging because there is a lack of high-quality evidence in this heterogeneous population. Epidemiological studies have shown that breast cancer mortality does not decrease substantially in the older population compared with younger adults. Recent data suggest a phenotype somewhat different from that of younger patients, also confirmed at the molecular level. Breast cancer biology has been incompletely deciphered in this age group. New therapeutic agents continue to expand the available treatment options at every stage, and for each subtype of breast cancer. In the estrogen receptor-positive subtype, agents to overcome endocrine resistance have been introduced; CDK 4/6 and mTOR inhibitors have already been approved in this setting. In addition, more potent agents targeting the HER2 pathway are actively being trialed. Besides trastuzumab, pertuzumab, or lapatinib, new agents like neratinib or PI3K inhibitors are currently being tested in clinical trials. Finally, even though chemotherapy remains the cornerstone of the treatment of triple negative tumors, alternative promising approaches such as immunotherapy, notably antibodies against PD-1/PD-L1 or targeted therapies (PARP or androgen inhibitors), are currently being investigated in this specific subtype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  2. DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin. 2016;66:31–42.

    Article  PubMed  Google Scholar 

  3. Bastiaannet E, Portielie JEA, van de Velde CJH, de Craen AJM, van der Velde S, Kuppen PJK, et al. Lack of survival gain for elderly women with breast cancer. Oncologist. 2011;16:415–23.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ruiz M, Reske T, Cefalu C, Estrada J. Differences in outcomes between elderly and nonelderly breast cancer patients in Louisiana. Am J Med Sci. 2013;346(5):377–80.

    Article  PubMed  Google Scholar 

  5. Jensen JD, Cold S, Nielsen MH, Jylling AM, Søe KL, Larsen LB, Ewertz M. Academy of Geriatric Cancer Research (AgeCare). Trends in breast cancer in the elderly in Denmark, 1980–2012. Acta Oncol. 2016;55(Suppl 1):59–64.

    Article  PubMed  Google Scholar 

  6. Albrand G, Terret C. Early breast cancer in the elderly. Assessment and management considerations. Drugs Aging. 2008;25(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  7. Biganzoli L, Wildiers H, Oakman C, Marotti L, Loibl S, Kunkler I, et al. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol. 2012;13(4):e148–60.

    Article  PubMed  Google Scholar 

  8. Freedman RA, Foster JC, Seisler DK, Lafky JM, Muss HB, Cohen HHJ, et al. Accrual of older patients with breast cancer to Alliance systemic therapy trials over time: protocol A151527. J Clin Oncol. 2017;35(4):421–31.

    Article  PubMed  Google Scholar 

  9. Hu X, Huang W, Fan M. Emerging therapies for breast cancer. J Hematol Oncol. 2017;10(1):98.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Diab SG, Elledge RM, Clark GM. Tumor characteristics and clinical outcomes of elderly women with breast cancer. J Natl Cancer Inst. 2000;92:550–6.

    Article  CAS  PubMed  Google Scholar 

  11. Louwman WJ, Vulto JC, Verhoeven RHA, Nieuwenhuijzen GAP, Coebergh JWW, Voogd AC. Clinical epidemiology of breast cancer in the elderly. Eur J Cancer. 2007;43(15):2242–52.

    Article  CAS  PubMed  Google Scholar 

  12. Ali AM, Greenberg D, Wishart GC, Pharoah P. Patient and tumour characteristics, management, and age-specific survival in women with breast cancer in the East of England. Br J Cancer. 2011;104(4):564–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Montroni I, Rocchi M, Santini D, Ceccarelli C, Ghignone F, Zaltoni D, et al. Has breast cancer in the elderly remained the same over recent decades? A comparison of two groups of patients 70 years or older treated for breast cancer twenty years apart. J Geriatr Oncol. 2014;5(3):260–5.

    Article  PubMed  Google Scholar 

  14. Wildiers H, Van Calster B, van de Poll-Franse LV, Hendrickx W, Røislien J, Smeets A, et al. Relationship between age and axillary lymph node involvement in women with breast cancer. J Clin Oncol. 2009;27(18):2931–7.

    Article  PubMed  Google Scholar 

  15. Ogunbiyi SO, Lee S, Mathew J, Cheung KL. Primary breast cancer in the elderly: a systematic literature review on histological type and clinical outcome. Future Oncol. 2015;11(2):259–65.

    Article  CAS  PubMed  Google Scholar 

  16. de Kruijf EM, Bastiaannet E, Rubertà F, de Craen AJ, Kuppen PJ, Smit VT, et al. Comparison of frequencies and prognostic effect of molecular subtypes between young and elderly breast cancer patients. Mol Oncol. 2014;8(5):1014–25.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jenkins EO, Deal AM, Anders CK, Prat A, Perou CM, Carey LA, Muss HB. Age-specific changes in intrinsic breast cancer subtypes: a focus on older women. Oncologist. 2014;19(10):1076–83.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Durbecq V, Ameye L, Veys I, Paesmans M, Desmedt C, Sirtaine N, et al. A significant proportion of elderly patients develop hormone-dependent “luminal-B” tumours associated with aggressive characteristics. Crit Rev Oncol Hematol. 2008;67(1):80–92.

    Article  CAS  PubMed  Google Scholar 

  19. Engels CC, Kiderlen M, Bastiaannet E, Mooyaart AL, van Vlierberghe R, Smit VT, et al. The clinical prognostic value of molecular intrinsic tumor subtypes in older breast cancer patients: a FOCUS study analysis. Mol Oncol. 2016;10(4):594–600.

    Article  CAS  PubMed  Google Scholar 

  20. Bergen ES, Tichy C, Berghoff AS, Rudas M, Dubsky P, Bago-Horvath Z, et al. Prognostic impact of breast cancer subtypes in elderly patients. Breast Cancer Res Treat. 2016;157:91–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Königsberg R, Pfeiler G, Klement T, Hammerschmid N, Brunner A, Zeillinger R, et al. Tumor characteristics and recurrence patterns in triple negative breast cancer: a comparison between younger (< 65) and elderly (≥ 65) patients. Eur J Cancer. 2012;48(16):2962–8.

    Article  PubMed  Google Scholar 

  22. Kaplan HG, Malmgren JA, Atwood MK. Triple-negative breast cancer in the elderly: prognosis and treatment. Breast J. 2017;23(6):630–7.

    Article  CAS  PubMed  Google Scholar 

  23. Azim HA Jr, Nguyen B, Brohée S, Zoppoli G, Sotiriou C. Genomic aberrations in young and elderly breast cancer patients. BMC Med. 2015;13:266.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ueno T, Emi M, Sato H, Ito N, Muta M, KUroi K, Toi M. Genome-wide copy number analysis in primary breast cancer. Expert Opin Ther Targets. 2012;16(Suppl 1):S31–5.

    Article  CAS  PubMed  Google Scholar 

  25. Climent J, Martinez-Climent JA, Blesa D, Garcia-Barchino MJ, Saez R, Sánchez-Izquierdo D, et al. Genomic loss of 18p predicts an adverse clinical outcome in patients with high-risk breast cancer. Clin Cancer Res. 2002;8(12):3863–9.

    CAS  PubMed  Google Scholar 

  26. Villarreal-Garza C, Cortes J, Andre F, Verma S. mTOR inhibitors in the management of hormone receptor-positive breast cancer; the latest evidence and future directions. Ann Oncol. 2012;23(10):2526–35.

    Article  CAS  PubMed  Google Scholar 

  27. Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–9.

    Article  CAS  PubMed  Google Scholar 

  28. Pritchard KI, Burris HA 3rd, Ito Y, Rugo HS, Dakhil S, Hortobagyi GN, et al. Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer. 2013;13(6):421–32.

    Article  CAS  PubMed  Google Scholar 

  29. Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jerusalem G, Mariani G, Ciruelos EM, Martin M, Tjan-Hejnen VC, Neven P, et al. Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). Ann Oncol. 2016;27(9):1719–25.

    Article  CAS  PubMed  Google Scholar 

  31. Tesch H, Grischke EM, Fasching P, Decker T, Uleer C, Schneeweiss A, et al. Results of the third interim analysis of the non-interventional trial BRAWO – subanalysis of patients aged < 70 years and ≥ 70 years. Cancer res. 2016;76(4 Suppl): Poster P4-13-06.

  32. Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negativemetastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718–24.

    Article  CAS  PubMed  Google Scholar 

  33. Baselga J, Im SA, Iwata H, Cortés J, De Laurentis M, Jiang Z, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(7):904–16.

    Article  CAS  PubMed  Google Scholar 

  34. Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning P, Janni W, et al. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19:87–100.

    Article  PubMed  Google Scholar 

  35. Royce M, Villanueva C, Ozguroglu M, Bachelot T, Azevedo S, Melo Cruz F, et al. BOLERO-4: phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (BC). Ann Oncol. 2016;27(Suppl 6):2220.

    Google Scholar 

  36. Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, et al. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013;31(2):195–202.

    Article  CAS  PubMed  Google Scholar 

  37. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3(11):1427–38.

    CAS  PubMed  Google Scholar 

  39. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomized phase 2 study. Lancet Oncol. 2015;16(1):25–35.

    Article  CAS  PubMed  Google Scholar 

  40. Finn RS, Crown JP, Ettl J, Schmidt M, Bondarenko IM, Lang I, et al. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Breast Cancer Res. 2016;18(1):67.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–36.

    Article  CAS  PubMed  Google Scholar 

  42. Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck H, et al. Palbociclib in combination with endocrine therapy in treatment-naïve and previously treated elderly women with HR+, HER2-, advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies. Cancer Res. 2017; 77(4 Suppl): Abstract P4-22-03.

  43. Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(17):1672–3.

    Article  PubMed  Google Scholar 

  44. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425–39.

    Article  CAS  PubMed  Google Scholar 

  45. Verma S, Bartlett CH, Schnell P, DeMichele AM, Loi S, Ro J, et al. Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist. 2016;21(10):1165–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.

    Article  CAS  PubMed  Google Scholar 

  47. Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218–24.

    Article  CAS  PubMed  Google Scholar 

  48. Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HER+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875–84.

    Article  PubMed  Google Scholar 

  49. Hodges-Gallagher L, Valentine CD, El Bader S, Kushner PJ. Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells. Breast Cancer Res Treat. 2007;105:297–309.

    Article  CAS  PubMed  Google Scholar 

  50. Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM, et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol. 2013;31(17):2128–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72.

    Article  CAS  PubMed  Google Scholar 

  52. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.

    Article  CAS  PubMed  Google Scholar 

  53. Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29(25):3366–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Slamon D, Euermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Brollo J, Curigliano G, Disalvatore D, Marrone BF, Criscitiello C, Bagnardi V, et al. Adjuvant trastuzumab in elderly with HER2-positive breast cancer: a systematic review of randomized controlled trials. Cancer Treat Rev. 2013;39(1):44–50.

    Article  CAS  PubMed  Google Scholar 

  56. Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012;60(24):2504–12.

    Article  CAS  PubMed  Google Scholar 

  57. Chavez-MacGregor M, Zhang N, Buchholz TA, Zhang Y, Niu J, Elting L, et al. Trastuzumab-related cardiotoxicity among older patients with breast cancer. J Clin Oncol. 2013;31(33):4222–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Leung HW, Chan AL. Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data. Expert Opin Drug Saf. 2015;14(11):1661–71.

    Article  CAS  PubMed  Google Scholar 

  59. Vaz-Luis I, Keating NL, Lin NU, Lii H, Winer EP, Freedman RA. Duration and toxicity of adjuvant trastuzumab in older patients with early-stage breast cancer: a population-based study. J Clin Oncol. 2014;32(9):927–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kaufman PA, Brufsky AM, Mayer M, Rugo HS, Tripathy D, Yood MU, et al. Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from registHER observational study. Breast Cancer Res Treat. 2012;135(3):875–83.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Grifiths RI, Lalla D, Herbert RJ, Doan JF, Brammer MG, Danese MD. Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab. Cancer Investig. 2011;29(9):573–84.

    Article  Google Scholar 

  62. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.

    Article  CAS  PubMed  Google Scholar 

  63. Miles D, Baselga J, Amadori D, Sunpaweravong P, Semiglazov V, Knott A, et al. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast Cancer Res Treat. 2013;142(1):89–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lenihan D, Suter T, Brammer M, Neate C, Ross G, Baselga J. Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab. Ann Oncol. 2012;23(3):791–800.

    Article  CAS  PubMed  Google Scholar 

  65. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–84.

    Article  CAS  PubMed  Google Scholar 

  66. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomized, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732–42.

    Article  PubMed  Google Scholar 

  68. Krop IE, Kim SB, Gonzàlez-Martin A, LoRusso PM, Ferrero JM, Smitt M, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomized, open-label, phase 3 trial. Lancet Oncol. 2014;15(7):689–99.

    Article  CAS  PubMed  Google Scholar 

  69. Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, et al. Trastuzumab emtansine versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomized open-label phase 3 trial. Lancet Oncol. 2017;18(6):743–54.

    Article  CAS  PubMed  Google Scholar 

  70. Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, et al. Feasibility and cardiac safety of trastuzumab emtansine after anthracycline-based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2-positive early-stage breast cancer. J Clin Oncol. 2015;33(10):1136–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–43.

    Article  CAS  PubMed  Google Scholar 

  72. Cetin B, Benekli M, Dane F, Boruban C, Gumus M, Oksuzoglu B, et al. Lapatinib plus capecitabine for HER2-positive advanced-stage breast cancer in elderly women: review of the Anatolian Society of Medical Oncology (ASMO) experience. Breast Care (Basel). 2013;8(1):67–70.

    Article  Google Scholar 

  73. Xu ZQ, Li N, Liu PJ, Gao L, Gao X, Tie XJ. Efficacy and safety of lapatinib and trastuzumab for HER2-positive breast cancer: a systematic review and meta-analysis of randomized controlled trials. BMJ Open. 2017;7(3):e013053.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 study. J Clin Oncol. 2012;30(21):2585–92.

    Article  CAS  PubMed  Google Scholar 

  75. Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367–77.

    Article  CAS  PubMed  Google Scholar 

  76. André F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580–91.

    Article  PubMed  Google Scholar 

  77. Bonotto M, Gerratana L, Poletto E, Driol P, Giangreco M, Russso S, et al. Measures of outcome in metastatic breast cancer: insights from a real-world scenario. Oncologist 2014;19:608–15.

  78. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-anaysis. Cancer Treat Rev. 2016;45:30–7.

    Article  CAS  PubMed  Google Scholar 

  80. Poropatich K, Fontanarosa J, Samant S, Sosman JA, Zhang B. Cancer immunotherapies: are they as effective in the elderly? Drugs Aging. 2017;34(8):567–81.

    Article  CAS  PubMed  Google Scholar 

  81. Casey G. The BRCA1 and BRCA2 breast cancer genes. Curr Opin Oncol. 1997;9(1):88–93.

    Article  CAS  PubMed  Google Scholar 

  82. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44.

    Article  CAS  PubMed  Google Scholar 

  83. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12(9):852–61.

    Article  CAS  PubMed  Google Scholar 

  84. Robson ME, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. New Engl J Med. 2017;377(6):523–33.

    Article  CAS  PubMed  Google Scholar 

  85. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005;24(29):4660–71.

    Article  CAS  PubMed  Google Scholar 

  86. Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27(5):812–8.

    Article  CAS  PubMed  Google Scholar 

  87. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res. 2013;19(19):5505–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23(31):7794–803.

    Article  CAS  PubMed  Google Scholar 

  89. Aapro M, Tjulandin S, Bhar P, Gradishar W. Weekly nab-paclitaxel is safe and effective in ≥ 65 years old patients with metastatic breast cancer: a post-hoc analysis. Breast. 2011;20(5):468–74.

    Article  PubMed  Google Scholar 

  90. von Minckwitz G, Conrad B, Reimer T, Decker T, Eidtmann H, Eiermann W, et al. A randomized phase 2 study comparing EC or CMF versus nab-paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high-risk early breast cancer (ICE II-GBG 52). Cancer. 2015;121(20):3639–48.

    Article  Google Scholar 

  91. Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomized study. Lancet. 2011;377(9769):914–23.

    Article  CAS  PubMed  Google Scholar 

  92. Muss H, Cortes J, Vahdat LT, Cardoso F, Twelves C, Wanders J, et al. Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist. 2014;19(4):318–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Sophie Darnis of the Centre Léon Bérard for medical editorial assistance.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Centre Léon Bérard, Regional Comprehensive Cancer Centre, Claude-Bernard Lyon-1 University, 28 rue Laennec, Lyon, France

    Catherine Terret & Chiara Russo

  2. Department of Geriatric Medicine, IRCCS University Hospital San Martino-IST, Genoa, Italy

    Chiara Russo

Authors
  1. Catherine Terret
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherine Terret.

Ethics declarations

Funding

No sources of funding were used to assist in the preparation of this review.

Conflict of interest

Catherine Terret and Chiara Russo have no conflicts of interest relevant to the content of this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Terret, C., Russo, C. Pharmacotherapeutic Management of Breast Cancer in Elderly Patients: The Promise of Novel Agents. Drugs Aging 35, 93–115 (2018). https://doi.org/10.1007/s40266-018-0519-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-018-0519-5

search

Navigation