Individualizing Local-Regional Therapy of Breast Cancer in the Elderly
Purpose of Review
The treatment of breast cancer in the elderly population requires a tailored approach. We summarize the current best evidence for personalized local-regional therapy in breast cancer patients older than 70.
Breast cancer treatment in older adults incorporates the use of geriatric assessment tools to best evaluate functional status and treatment tolerability while accounting for the biologic profile of the disease. Surgical resection of the primary tumor with lymph node evaluation remains the cornerstone of local-regional control. Recent clinical trials demonstrate that surgery and radiation therapy may, however, be safely omitted in selected patients who are eligible for primary endocrine therapy. In patients with high-risk node-positive disease, DFS can be improved by systemic chemotherapy, but potential toxicity should be carefully considered in this population.
Patient-specific evaluation of the risks of both under- and over-treatment of breast cancer in the older adult is essential for delivering optimal care in this population.
KeywordsBreast cancer Local-regional management Geriatric assessment Elderly
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers with particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Lewis DR, Chen H-S, Cockburn MG, Wu XC, Stroup AM, Midthune DN, et al. Early estimates of SEER cancer incidence, 2014. Cancer. 2017;123(13):2524–34. https://doi.org/10.1002/cncr.30630.
- 5.• Hurria A, Levit LA, Dale W, Mohile SG, Muss HB, Fehrenbacher L, et al. Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology statement. J Clin Oncol. 2015;33(32):3826–33. https://doi.org/10.1200/JCO.2015.63.0319. ASCO recommendations for improving representation of older adults in clinical trails and implementing evidence based guidelines in this population.
- 7.Mehnert A, Koch U. Psychological comorbidity and health-related quality of life and its association with awareness, utilization, and need for psychosocial support in a cancer register-based sample of long-term breast cancer survivors. J Psychosom Res. 2008;64(4):383–91. https://doi.org/10.1016/j.jpsychores.2007.12.005.CrossRefPubMedGoogle Scholar
- 8.DeMichele A, Putt M, Zhang Y, Glick JH, Norman S. Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma: evidence from a tertiary care cohort of chemotherapy-eligible patients. Cancer. 2003;97(9):2150–9. https://doi.org/10.1002/cncr.11338.CrossRefPubMedGoogle Scholar
- 14.Berglund A, Wigertz A, Adolfsson J, Ahlgren J, Fornander T, Wärnberg F, et al. Impact of comorbidity on management and mortality in women diagnosed with breast cancer. Breast Cancer Res Treat. 2012;135(1):281–9. https://doi.org/10.1007/s10549-012-2176-4.
- 16.Freyer G, Geay J-F, Touzet S, Provencal J, Weber B, Jacquin JP, et al. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study. Ann Oncol. 2005;16(11):1795–800. https://doi.org/10.1093/annonc/mdi368.
- 19.• Muss HB, Berry DA, Cirrincione CT, et al. Standard chemotherapy versus capcitabine for older women with early stage breast cancer: an update of CALGB/CTSU/alliance 49907. J Clin Oncol. 2015;33(15_suppl):1022–2. https://doi.org/10.1200/jco.2015.33.15_suppl.1022. Clinical trial that demonstrates significant benefit of standard polychemotherapy over single-agent oral chemotherapy.
- 20.Besic N, Besic H, Peric B, Pilko G, Petric R, Zmuc J, et al. Surgical treatment of breast cancer in patients aged 80 years or older—how much is enough? BMC Cancer. 2014;14:700.Google Scholar
- 21.Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the north central cancer treatment group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–8. https://doi.org/10.1200/JCO.2007.13.5467.
- 24.•• Jolly TA, Deal AM, Nyrop KA, Williams GR, Pergolotti M, Wood WA, et al. Geriatric assessment-identified deficits in older cancer patients with normal performance status. Oncologist. 2015;20(4):379–85. Landmark paper addressing the deficits in existing geriatric assessment tools and provides a brief geriatric assessment tool which can be implemented in routine practice Google Scholar
- 25.Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189–198.Google Scholar
- 28.Jacobsen PB, Donovan KA, Trask PC, Fleishman SB, Zabora J, Baker F, et al. Screening for psychologic distress in ambulatory cancer patients. Cancer. 2005;103(7):1494–502. https://doi.org/10.1002/cncr.20940.
- 30.Robb C, Haley WE, Balducci L, Extermann M, Perkins EA, Small BJ, et al. Impact of breast cancer survivorship on quality of life in older women. Crit Rev Oncol Hematol. 2007;62(1):84–91. https://doi.org/10.1016/j.critrevonc.2006.11.003.
- 31.Kreling B, Figueiredo MI, Sheppard VL, Mandelblatt JS. A qualitative study of factors affecting chemotherapy use in older women with breast cancer: barriers, promoters, and implications for intervention. Psychooncology. 2006;15(12):1065–76. https://doi.org/10.1002/pon.1042.CrossRefPubMedGoogle Scholar
- 33.Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014;383(9917):603–13. https://doi.org/10.1016/S0140-6736(13)61950-9.
- 34.Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. The Lancet Oncology. 2013;14(13):1269–77. https://doi.org/10.1016/S1470-2045(13)70497-2.
- 35.Neumaier C, Elena S, Grit W, Yasser AM, Uta KT, Anke K, et al. TARGIT-E(lderly)—prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer. BMC Cancer. 2012;12:171. https://doi.org/10.1186/1471-2407-12-171.
- 36.Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002;20(20):4141–9. https://doi.org/10.1200/JCO.2002.11.101.
- 38.•• Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31(19):2382–7. https://doi.org/10.1200/JCO.2012.45.2615. Landmark clinical trial demonstrating equivalent outcomes in older patients receiving tamoxifen with or without radiation therapy.
- 41.Gennari R, Curigliano G, Rotmensz N, Robertson C, Colleoni M, Zurrida S, et al. Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients. Cancer. 2004;101(6):1302–10. https://doi.org/10.1002/cncr.20535.
- 42.Kaur P, Santillan AA, McGuire K, Turaga KK, Shamehdi C, Meade T, et al. The surgical treatment of breast cancer in the elderly: a single institution comparative review of 5235 patients with 1028 patients >/=70 years. Breast J. 2012;18(5):428–35. https://doi.org/10.1111/j.1524-4741.2012.01272.x.
- 43.Eagle KA, Berger PB, Calkins H, Chaitman BR, Ewy GA, Fleischmann KE, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery—executive summary a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to update the 1996 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation. 2002;105(10):1257–67.Google Scholar
- 47.Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41. https://doi.org/10.1056/NEJMoa022152.
- 48.Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227–32.Google Scholar
- 49.Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. N Engl J Med 1995;333(22):1444–1455. doi: https://doi.org/10.1056/NEJM199511303332202
- 50.Pierga J-Y, Girre V, Laurence V, Asselain B, Diéras V, Jouve M, et al. Characteristics and outcome of 1755 operable breast cancers in women over 70 years of age. Breast. 2004;13(5):369–75.Google Scholar
- 52.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). The Lancet Oncology. 2012;13(4):e148–60. https://doi.org/10.1016/S1470-2045(11)70383-7.
- 53.Bazan JG, Bittoni MA, Fisher JL, White JR. Trends in mastectomy rates over time in elderly women with stage I, hormone-sensitive breast cancer: A SEER-based study. J Clin Oncol. 2016;34(15_suppl):1063–3. https://doi.org/10.1200/JCO.2016.34.15_suppl.1063.
- 55.Girotto JA, Schreiber J, Nahabedian MY. Breast reconstruction in the elderly: preserving excellent quality of life. Ann Plast Surg. 2003;50(6):572–8. https://doi.org/10.1097/01.SAP.0000069064.68579.19.CrossRefPubMedGoogle Scholar
- 57.• Reddy KG, Strassle PD, McGuire KP. Role of age, tumor grade, and radiation therapy on immediate postmastectomy breast reconstruction. Clin Breast Cancer. December 2017; https://doi.org/10.1016/j.clbc.2017.11.021. Recent retrospective study demonstrating the low rates of post mastectomy breast reconstruction with advancing age.
- 58.Burnier P, Hudry D, See L-A, Duvernay A, Roche M, Loustalot C, et al. Patient age and breast resection weight affect immediate postmastectomy breast reconstruction in ductal carcinoma in situ. J Plast Reconstr Aesthet Surg. 2016;69(1):37–41. https://doi.org/10.1016/j.bjps.2015.09.023.
- 59.Martelli G, Miceli R, Daidone MG, Vetrella G, Cerrotta AM, Piromalli D, et al. Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up. Ann Surg Oncol. 2011;18(1):125–33.Google Scholar
- 60.Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of international breast cancer study group trial 10–93. J Clin Oncol. 2006;24(3):337–344. doi: https://doi.org/10.1200/JCO.2005.01.5784.
- 61.Martelli G, Miceli R, Daidone MG, Vetrella G, Cerrotta AM, Piromalli D, et al. Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up. Ann Surg Oncol. 2011;18(1):125–33.Google Scholar
- 62.Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11(10):927–33.Google Scholar
- 64.•• Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (alliance) randomized clinical trial. JAMA. 2017;318(10):918–26. https://doi.org/10.1001/jama.2017.11470. Landmark clinical trial demonstrating equivalent 10 year overall and disease free survival in early stage breast cancer patients receiving axillary lymph node dissection or sentinel lymph node dissection alone.
- 65.Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, et al. Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol. 2005;16(3):383–8. https://doi.org/10.1093/annonc/mdi089.
- 66.Cote R, Giuliano AE, Hawes D, et al. ACOSOG Z0010: A multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer. J Clin Oncol. 2010;28(18_suppl):CRA504–4. https://doi.org/10.1200/jco.2010.28.18_suppl.cra504.
- 67.Biganzoli L. 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. 13(4):e148–60.Google Scholar
- 68.Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJH, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10. https://doi.org/10.1016/S1470-2045(14)70460-7.
- 70.Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle C, Harnett AN, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group Lancet. 1996;348(9029):708–13.Google Scholar
- 71.Winzer K-J, Sauerbrei W, Braun M, Liersch T, Dunst J, Guski H, et al. Radiation therapy and tamoxifen after breast-conserving surgery: updated results of a 2 x 2 randomised clinical trial in patients with low risk of recurrence. Eur J Cancer. 2010;46(1):95–101. https://doi.org/10.1016/j.ejca.2009.10.007.
- 72.Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41.Google Scholar
- 74.Blamey RW. Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur J Cancer. 49(10):2294–302.Google Scholar
- 76.•• Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16(3):266–73. https://doi.org/10.1016/S1470-2045(14)71221-5. Landmark clinical trial providing evidence for safety of omitting radiation therapy in carefully selected older breast cancer patients. CrossRefPubMedGoogle Scholar
- 79.Colleoni M, Giobbie-Hurder A, Regan MM, Thürlimann B, Mouridsen H, Mauriac L, et al. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J Clin Oncol. 2011;29(9):1117–24. https://doi.org/10.1200/JCO.2010.31.6455.
- 81.Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386(10001):1353–1361. doi: https://doi.org/10.1016/S0140-6736(15)60908-4.
- 82.Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N, et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19(4):980–91. https://doi.org/10.1200/JCO.2001.19.4.980.
- 83.van de Vijver MJ, He YD, van 't Veer LJ, Dai H, Hart AAM, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009. https://doi.org/10.1056/NEJMoa021967.
- 84.Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DSA, Nobel AB, et al. Concordance among gene-expression–based predictors for breast cancer. N Engl J Med. 2006;355(6):560–9. https://doi.org/10.1056/NEJMoa052933.
- 86.• Petkov VI, Miller DP, Howlader N, et al. Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. Npj Breast Cancer. 2016;2(1):e0128345. https://doi.org/10.1038/npjbcancer.2016.17. Recent retrospective database study demonstrating the role of 21-gene Recurrence Score in predicting the benefit of chemotherapy. CrossRefGoogle Scholar
- 87.Elkin EB, Hurria A, Mitra N, Schrag D, Panageas KS. Adjuvant chemotherapy and survival in older women with hormone receptor-negative breast cancer: assessing outcome in a population-based, observational cohort. J Clin Oncol. 2006;24(18):2757–64. https://doi.org/10.1200/JCO.2005.03.6053.CrossRefPubMedGoogle Scholar
- 88.Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360(20):2055–65. https://doi.org/10.1056/NEJMoa0810266.
- 89.Minckwitz v G, Conrad B, Reimer T, 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. https://doi.org/10.1002/cncr.29506. CrossRefGoogle Scholar
- 91.Kornblith AB, Lan L, Archer L, Partridge A, Kimmick G, Hudis C, et al. Quality of life of older patients with early-stage breast cancer receiving adjuvant chemotherapy: a companion study to cancer and leukemia group B 49907. J Clin Oncol. 2011;29(8):1022–8. https://doi.org/10.1200/JCO.2010.29.9859.
- 92.•• Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–205. https://doi.org/10.1016/S0140-6736(16)32616-2. Landmark clinical trial demonstrating the benefit of 1-year of trastuzumab in HER2-positive breast cancer patients. CrossRefPubMedPubMedCentralGoogle Scholar
- 93.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. https://doi.org/10.1056/NEJMoa052306.
- 94.Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23(31):7811–9. https://doi.org/10.1200/JCO.2005.02.4091.