Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2012

Open Access 01-10-2012 | Epidemiology

Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study

Authors: Peter A. Kaufman, Adam M. Brufsky, Musa Mayer, Hope S. Rugo, Debu Tripathy, Marianne Ulcickas Yood, Shibao Feng, Lisa I. Wang, Cheng S. Quah, Denise A. Yardley

Published in: Breast Cancer Research and Treatment | Issue 3/2012

Login to get access

Abstract

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65–74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS.
Literature
1.
go back to reference Balducci L, Phillips DM (1998) Breast cancer in older women. Am Fam Physician 58:1163–1172PubMed Balducci L, Phillips DM (1998) Breast cancer in older women. Am Fam Physician 58:1163–1172PubMed
2.
go back to reference Downey L, Livingston R, Stopeck A (2007) Diagnosing and treating breast cancer in elderly women: a call for improved understanding. J Am Geriatr Soc 55:1636–1644PubMedCrossRef Downey L, Livingston R, Stopeck A (2007) Diagnosing and treating breast cancer in elderly women: a call for improved understanding. J Am Geriatr Soc 55:1636–1644PubMedCrossRef
3.
go back to reference Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer Am, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winder EP, CALGB Investigators (2009) Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 360:2055–2065PubMedCrossRef Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer Am, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winder EP, CALGB Investigators (2009) Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 360:2055–2065PubMedCrossRef
4.
go back to reference Crivellari D, Aapro M, Leonard R, von Minckwitz G, Brain E, Goldhirsch A, Veronesi A, Muss H (2007) Breast cancer in the elderly. J Clin Oncol 25:1882–1890PubMedCrossRef Crivellari D, Aapro M, Leonard R, von Minckwitz G, Brain E, Goldhirsch A, Veronesi A, Muss H (2007) Breast cancer in the elderly. J Clin Oncol 25:1882–1890PubMedCrossRef
5.
go back to reference Pallis AG, Fortpied C, Wedding U, Van Nes MC, Penninckx B, Ring A, Lacombe D, Monfardini S, Scalliet P, Wildiers H (2012) EORTC elderly task force position paper: approach to the older cancer patient. Eur J Cancer 46:1502–1513CrossRef Pallis AG, Fortpied C, Wedding U, Van Nes MC, Penninckx B, Ring A, Lacombe D, Monfardini S, Scalliet P, Wildiers H (2012) EORTC elderly task force position paper: approach to the older cancer patient. Eur J Cancer 46:1502–1513CrossRef
6.
go back to reference Talarico L, Chen G, Pazdur R (2004) Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 22:4626–4631PubMedCrossRef Talarico L, Chen G, Pazdur R (2004) Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 22:4626–4631PubMedCrossRef
7.
go back to reference Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061–2067PubMedCrossRef Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061–2067PubMedCrossRef
8.
go back to reference Townsley CA, Selby R, Siu LL (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 23:3112–3124PubMedCrossRef Townsley CA, Selby R, Siu LL (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 23:3112–3124PubMedCrossRef
9.
go back to reference Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH (2007) Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 25:3808–3815PubMedCrossRef Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH (2007) Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 25:3808–3815PubMedCrossRef
10.
go back to reference Biganzoli L, Wildiers H, Oakman C, Marotti L, Loibl S, Kunkler I, Reed M, Ciatto S, Voogd AC, Brain E, Cutuli B, Terret C, Gosney M, Aapro M, Audisio R (2012) 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:e148–e160PubMedCrossRef Biganzoli L, Wildiers H, Oakman C, Marotti L, Loibl S, Kunkler I, Reed M, Ciatto S, Voogd AC, Brain E, Cutuli B, Terret C, Gosney M, Aapro M, Audisio R (2012) 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:e148–e160PubMedCrossRef
11.
go back to reference Du X, Goodwin JS (2001) Patterns of use of chemotherapy for breast cancer in older women: findings from Medicare claims data. J Clin Oncol 19:1455–1461PubMed Du X, Goodwin JS (2001) Patterns of use of chemotherapy for breast cancer in older women: findings from Medicare claims data. J Clin Oncol 19:1455–1461PubMed
12.
go back to reference Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285:885–892PubMedCrossRef Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285:885–892PubMedCrossRef
13.
go back to reference Townsley C, Pond GR, Peloza B, Kok J, Naidoo K, Dale D, Herbert C, Holowaty E, Straus S, Siu LL (2005) Analysis of treatment practices for elderly cancer patients in Ontario, Canada. J Clin Oncol 23:3802–3810PubMedCrossRef Townsley C, Pond GR, Peloza B, Kok J, Naidoo K, Dale D, Herbert C, Holowaty E, Straus S, Siu LL (2005) Analysis of treatment practices for elderly cancer patients in Ontario, Canada. J Clin Oncol 23:3802–3810PubMedCrossRef
14.
go back to reference Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schäfer P, Kurtz J, Sappino AP, Vlastos G (2003) Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 21:3580–3587PubMedCrossRef Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schäfer P, Kurtz J, Sappino AP, Vlastos G (2003) Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 21:3580–3587PubMedCrossRef
15.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedCrossRef Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedCrossRef
16.
go back to reference Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 49:650–655PubMedCrossRef Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 49:650–655PubMedCrossRef
17.
go back to reference Estevez L, Seidman A (2003) HER2-positive breast cancer: incidence, prognosis, and treatment options. Am J Cancer 2:169–179CrossRef Estevez L, Seidman A (2003) HER2-positive breast cancer: incidence, prognosis, and treatment options. Am J Cancer 2:169–179CrossRef
18.
go back to reference Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA (2011) Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res 14:4834–4843CrossRef Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA (2011) Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res 14:4834–4843CrossRef
20.
go back to reference Monfardini S, Yancik R (1993) Cancer in the elderly: meeting the challenge of an aging population. J Natl Cancer Inst 85:532–538PubMedCrossRef Monfardini S, Yancik R (1993) Cancer in the elderly: meeting the challenge of an aging population. J Natl Cancer Inst 85:532–538PubMedCrossRef
21.
go back to reference Du XL, Xia R, Burau K, Liu C-C (2005) Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998–2005. Med Oncol 28:S80–S90CrossRef Du XL, Xia R, Burau K, Liu C-C (2005) Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998–2005. Med Oncol 28:S80–S90CrossRef
22.
go back to reference Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, Martino S, Gralow JR, Dakhil SR, Ingle JN, Winer EP, Gelmon KA, Gersh BJ, Jaffe AS, Rodeheffer RJ (2008) 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 26:1231–1238PubMedCrossRef Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, Martino S, Gralow JR, Dakhil SR, Ingle JN, Winer EP, Gelmon KA, Gersh BJ, Jaffe AS, Rodeheffer RJ (2008) 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 26:1231–1238PubMedCrossRef
23.
go back to reference Serrano C, Cortés J, De Mattos-Arruda L, Bellet M, Gómez P, Saura C, Pérez J, Vidal M, Muñoz-Couselo E, Carreras MJ, Sánchez-Ollé G, Tabernero J, Baselga J, Di Cosimo S (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902PubMedCrossRef Serrano C, Cortés J, De Mattos-Arruda L, Bellet M, Gómez P, Saura C, Pérez J, Vidal M, Muñoz-Couselo E, Carreras MJ, Sánchez-Ollé G, Tabernero J, Baselga J, Di Cosimo S (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902PubMedCrossRef
24.
go back to reference Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D’Amico R (2012) Trastuzumab containing regimens for early breast cancer. Cochrane Database of Syst Rev 4:CD006243 Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D’Amico R (2012) Trastuzumab containing regimens for early breast cancer. Cochrane Database of Syst Rev 4:CD006243
25.
go back to reference Tarantini L, Cioffi G, Gori S, Tuccia F, Boccardi L, Bovelli D, Lestuzzi C, Maurea N, Oliva S, Russo G, Faggiano P, Italian Cardio-Oncologic Network (2012) Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail 18:113–119PubMedCrossRef Tarantini L, Cioffi G, Gori S, Tuccia F, Boccardi L, Bovelli D, Lestuzzi C, Maurea N, Oliva S, Russo G, Faggiano P, Italian Cardio-Oncologic Network (2012) Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail 18:113–119PubMedCrossRef
26.
go back to reference Griffiths RI, Lalla D, Herbert RJ, Doan JF, Brammer MG, Danese MD (2011) Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab. Cancer Invest 29:573–584PubMedCrossRef Griffiths RI, Lalla D, Herbert RJ, Doan JF, Brammer MG, Danese MD (2011) Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab. Cancer Invest 29:573–584PubMedCrossRef
27.
go back to reference Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704PubMedCrossRef Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704PubMedCrossRef
28.
go back to reference Pienkowski T, Zielinski CC (2010) Trastuzumab treatment in patients with breast cancer and metastatic CNS disease. Ann Oncol 21:917–924PubMedCrossRef Pienkowski T, Zielinski CC (2010) Trastuzumab treatment in patients with breast cancer and metastatic CNS disease. Ann Oncol 21:917–924PubMedCrossRef
29.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef
30.
go back to reference Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O’Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23:4265–4274PubMedCrossRef Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O’Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23:4265–4274PubMedCrossRef
Metadata
Title
Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study
Authors
Peter A. Kaufman
Adam M. Brufsky
Musa Mayer
Hope S. Rugo
Debu Tripathy
Marianne Ulcickas Yood
Shibao Feng
Lisa I. Wang
Cheng S. Quah
Denise A. Yardley
Publication date
01-10-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2209-z

Other articles of this Issue 3/2012

Breast Cancer Research and Treatment 3/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine