Systemic Treatment of Metastatic Breast Cancer in Older Adults

  • Anna Rachelle Mislang
  • Laura Biganzoli
  • Etienne BrainEmail author
Living reference work entry


The management of older adults with breast cancer poses a challenging dilemma to most treating oncologists given the under-representation of older age groups in most pivotal clinical trials. Older patients are at risk of undertreatment, which may be due to physician bias and/or patient preference. There is mounting evidence suggesting that older patients with breast cancer may derive as much benefit from treatment as their younger counterparts. However, generalizing treatment for all older breast cancer patients without further health assessment poses the risk of over-treatment. Although the efficacy outcomes may be similar across age groups, the tolerance to toxicity may differ, as determined mostly by comorbidities, organ function, and aging heterogeneity. In metastatic breast cancer, the main goal of care is to offer the least toxic treatment that can control symptoms, prolong survival, and preserve the quality of life. Therefore, defining the goals of treatment while carefully assessing the overall health status in addition to risk-benefit ratio is paramount to the treatment decision-making.


Breast cancer Older adults Systemic therapy Metastasis 


  1. Aapro M, Bernard-Marty C, Brain EG, et al. Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. Ann Oncol. 2011a;22(2):257–67.CrossRefPubMedGoogle Scholar
  2. Aapro M, Tjulandin S, Bhar P, et al. Weekly nab-paclitaxel is safe and effective in >/=65 years old patients with metastatic breast cancer: a post-hoc analysis. Breast. 2011b;20(5):468–74.CrossRefPubMedGoogle Scholar
  3. Addeo R, Sgambato A, Cennamo G, et al. Low-dose metronomic oral administration of vinorelbine in the first-line treatment of elderly patients with metastatic breast cancer. Clin Breast Cancer. 2010;10(4):301–6.CrossRefPubMedGoogle Scholar
  4. American Cancer Society. Cancer facts & figures 2015–2016. Atlanta: American Cancer Society; 2015.Google Scholar
  5. Bajetta E, Procopio G, Celio L, et al. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol: Off J Am Soc Clin Oncol. 2005;23(10):2155–61.CrossRefGoogle Scholar
  6. Barrios CH, Anton A, Delaloge S, et al. Safety of trastuzumab emtansine (T-DM1) in 373 patients 65 years or older with HER2-positive advanced breast cancer: a subgroup analysis of the Kamilla study. J Clin Oncol: Off J Am Soc Clin Oncol. 2015; 33(suppl; abstr 603).Google Scholar
  7. Basso U, Roma A, Brunello A, et al. Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (>/= 70 years). J Geriatr Oncol. 2013;4(4):340–5.CrossRefPubMedGoogle Scholar
  8. Baweja M, Suman VJ, Fitch TR, et al. Phase II trial of oral vinorelbine for the treatment of metastatic breast cancer in patients > or = 65 years of age: an NCCTG study. Ann Oncol. 2006;17(4):623–9.CrossRefPubMedGoogle Scholar
  9. Biganzoli LWH, Oakman C, Marotti L, Loibl S, Kunkler I, Reed M, Ciatto S, Voogd AC, Brain E, 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.CrossRefPubMedGoogle Scholar
  10. Biganzoli L, Lichtman S, Michel JP, et al. Oral single-agent chemotherapy in older patients with solid tumours: a position paper from the International Society of Geriatric Oncology (SIOG). Eur J Cancer. 2015;51:2491.CrossRefPubMedGoogle Scholar
  11. Biganzoli L, Aapro M, Loibl S, et al. Taxanes in the treatment of breast cancer: have we better defined their role in older patients? A position paper from a SIOG Task Force. Cancer Treat Rev. 2016;43:19–26.CrossRefPubMedGoogle Scholar
  12. Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 2017;28(1):16–33.Google Scholar
  13. Crown JP, Burris HA 3rd, Boyle F, et al. Pooled analysis of diarrhea events in patients with cancer treated with lapatinib. Breast Cancer Res Treat. 2008;112(2):317–25.CrossRefPubMedGoogle Scholar
  14. Debled M, Madranges N, Mertens C, et al. First-line chemotherapy for metastatic breast cancer in patients >/=75 years: a retrospective single-centre analysis. Crit Rev Oncol Hematol. 2011;80(1):171–9.CrossRefPubMedGoogle Scholar
  15. Del Mastro LPF, Repetto L, et al. Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer). Ann Oncol. 2005;16:253–8.CrossRefPubMedGoogle Scholar
  16. Dieras V, Harbeck N, Budd GT, et al. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. J Clin Oncol: Off J Am Soc Clin Oncol. 2014;32(25):2750–7.CrossRefGoogle Scholar
  17. Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ III, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377–86.CrossRefPubMedGoogle Scholar
  18. Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC cancer base No. 11 (internet). Lyon: International Agency for Research on Cancer; 2013.Google Scholar
  19. Finn RS, Crown JP, Lang I, 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 randomised phase 2 study. Lancet Oncol. 2015;16(1):25–35.CrossRefPubMedGoogle Scholar
  20. Finn RS, Crown JP, Ettl J, 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: BCR. 2016;18(1):67.CrossRefPubMedGoogle Scholar
  21. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–43.CrossRefPubMedGoogle Scholar
  22. Gradishar WJ, Tjulandin S, Davidson N, 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: Off J Am Soc Clin Oncol. 2005;23(31):7794–803.CrossRefGoogle Scholar
  23. Harris CA, Ward RL, Dobbins TA, et al. The efficacy of HER2-targeted agents in metastatic breast cancer: a meta-analysis. Ann Oncol. 2011;22(6):1308–17.CrossRefPubMedGoogle Scholar
  24. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.CrossRefPubMedGoogle Scholar
  25. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol: Off J Am Soc Clin Oncol. 2011;29(25):3457–65.CrossRefGoogle Scholar
  26. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2016;34(20):2366–71.CrossRefGoogle Scholar
  27. Jerusalem G, Mariani G, Ciruelos EM, et al. Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-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.CrossRefPubMedGoogle Scholar
  28. Kaufman PA, Brufsky AM, Mayer M, et al. Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Cancer Res Treat. 2012;135(3):875–83.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Kotsori AA, Noble JL, Ashley S, et al. Moderate dose capecitabine in older patients with metastatic breast cancer: a standard option for first line treatment? Breast. 2010;19(5):377–81.CrossRefPubMedGoogle Scholar
  30. Krop IE, Kim S-B, González-Martín A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(7):689–99.CrossRefPubMedGoogle Scholar
  31. Lichtman SM, Hurria A, Cirrincione CT, et al. Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840. Ann Oncol. 2012;23(3):632–8.CrossRefPubMedGoogle Scholar
  32. Miles D, Baselga J, Amadori D, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Mislang AR, Orlando L, Pistelli M, et al. Weekly nab-paclitaxel (NP) in older breast cancer (BC) patients: prospective evaluation of treatment (tx) compliance and adverse events (AE) from the EFFECT trial. 15th Annual Conference of the International Society of Geriatric Oncology (SIOG). J Geriatr Oncol. 2015; S34.Google Scholar
  34. Muss H, Cortes J, Vahdat LT, et al. Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist. 2014;19(4):318–27.CrossRefPubMedPubMedCentralGoogle Scholar
  35. O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10(Suppl 3):20–9.CrossRefPubMedGoogle Scholar
  36. Potthoff KNA, Söling U, Hansen R, Salat C, Grebhardt S, Marschner N. Efficacy and safety of nab-paclitaxel in patients with metastatic breast cancer: final results of the non-interventional study NABUCCO (41st ESMO Congress 2016). Ann Oncol. 2016; 27(S6):abstr 236P.Google Scholar
  37. Pritchard KI, Burris HA 3rd, Ito Y, 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. e428CrossRefPubMedGoogle Scholar
  38. Rocca A, Farolfi A, Bravaccini S, et al. Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother. 2014;15(3):407–20.CrossRefPubMedGoogle Scholar
  39. Rugo HS, Turner NC, Finn RS, et al. Palbociclib in combination with endocrine therapy in treatment-naive and previously treated elderly women with HR+, HER2– advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies. San Antonio Breast Cancer Symposium. San Antonio; 2016.Google Scholar
  40. Sorio R, Robieux I, Galligioni E, et al. Pharmacokinetics and tolerance of vinorelbine in elderly patients with metastatic breast cancer. Eur J Cancer. 1997;33(2):301–3.CrossRefPubMedGoogle Scholar
  41. Steger G, PE, Haslbauer F, Egle D, Galid A, Sliwa T, Lang A, Kühr T, Petzer A, Ruckser R, Mlineritsch B, Greil R, Seifert M, Singer C, Andel J, Kwasny W, Marth C, Pichler P, Tinchon C, Bartsch R. Safety and effectiveness of nab-paclitaxel in young and elderly patients with metastatic breast cancer: a prospective, multicenter non-interventional study (41st ESMO Congress 2016). Ann Oncol. 2016; 27(S6):abstr 241P.Google Scholar
  42. Sud S, Lai P, Zhang T, et al. Chemotherapy in the oldest old: the feasibility of delivering cytotoxic therapy to patients 80 years old and older. J Geriatr Oncol. 2015;6(5):395–400.CrossRefPubMedGoogle Scholar
  43. ten Tije AJ, Verweij J, Carducci MA, et al. Prospective evaluation of the pharmacokinetics and toxicity profile of docetaxel in the elderly. J Clin Oncol: Offi J Am Soc Clin Oncol. 2005;23(6):1070–7.CrossRefGoogle Scholar
  44. Turner NC, Ro J, Andre F, et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.CrossRefPubMedGoogle Scholar
  45. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Wan S, Jubelirer S. Geographic access and age-related variation in chemotherapy use in elderly with metastatic breast cancer. Breast Cancer Res Treat. 2015;149(1):199–209.CrossRefPubMedGoogle Scholar
  47. Weber BL, Vogel C, Jones S, et al. Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 1995;13(11):2722–30.CrossRefGoogle Scholar
  48. Willemsen AECAB, van Herpen C, Schneider TC, de Wit D, Kapitejn E, van Erp NP.. The influence of old age on everolimus exposure in patients with cancer. Abstract Book of the 41st ESMO Congress (ESMO 2016). Coppenhagen; 2016. p. 90.Google Scholar

Copyright information

© Crown 2018

Authors and Affiliations

  • Anna Rachelle Mislang
    • 1
    • 2
  • Laura Biganzoli
    • 1
  • Etienne Brain
    • 3
    Email author
  1. 1.Medical Oncology DepartmentNuovo Ospedale-Santo Stefano, Instituto Toscano TumoriPratoItaly
  2. 2.Cancer Clinical Trials Unit, Department of Medical OncologyRoyal Adelaide HospitalAdelaideAustralia
  3. 3.Department of Medical OncologyInstitut Curie/Hôpital René HugueninSaint-CloudFrance

Section editors and affiliations

  • Etienne Brain
    • 1
  1. 1.Department of Medical Oncology, Institute CurieHôpital René HugueninSaint-CloudFrance

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