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Erschienen in: Breast Cancer Research and Treatment 2/2013

01.01.2013 | Clinical trial

Effect of HER2 status on distant recurrence in early stage breast cancer

verfasst von: Kenneth R. Hess, Francisco J. Esteva

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2013

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Abstract

It has long been recognized in breast cancer that the effect of hormone receptor (HR) status on recurrence rates varies over time and with the site of recurrence. However, there is relatively little in the literature on the effect of human epidermal growth factor receptor 2 (HER2) on recurrence patterns. We wanted to assess whether the effect of HER2 status on the risk of distant recurrence changed over time and/or with HR status and whether these relationships varied with site of recurrence. We retrospectively studied 11,011 women diagnosed with stage I, II, or III breast cancer after 1997 who had data on HR status and HER2 status. 20 % were HR negative and HER2 negative (so-called “triple-negatives”), 7 % were HR negative and HER2 positive, 64 % were HR positive and HER2 negative, and 10 % were HR positive and HER2 positive. The estimated overall cumulative incidence of developing distant metastases is 20 % at 4 years, 30 % at 8 years, and 36 % at 12 years. The 12-year cumulative incidence was 23 % for bone, 16 % for liver, 14 % for lung, 13 % for distant lymph node, 10 % for brain, and 8 % for pleura. After adjusting for potential confounding factors, the nature of the effect of HER2 on recurrence rates was found to differ markedly across the sites of recurrence. For brain and pleura recurrences, the effect of HER2 depended on HR status in ways that significantly changed over time. For bone recurrences, the effect of HER2 did not depend on HR status, but did change significantly over time. For liver and distant lymph node recurrences, there was a significant effect of HER2 status that did not change with time or HR status. For lung recurrences, rates did not significantly vary with HER2 status.
Literatur
1.
Zurück zum Zitat Hess KR, Pusztai L, Buzdar AU, Hortobagyi GN (2003) Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat 78:105–118PubMedCrossRef Hess KR, Pusztai L, Buzdar AU, Hortobagyi GN (2003) Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat 78:105–118PubMedCrossRef
2.
Zurück zum Zitat Dawood S, Broglio K, Esteva FJ et al (2008) Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 19:1242–1248PubMedCrossRef Dawood S, Broglio K, Esteva FJ et al (2008) Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 19:1242–1248PubMedCrossRef
3.
Zurück zum Zitat Peintinger F, Buzdar AU, Kuerer HM et al (2008) Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Ann Oncol 19:2020–2025PubMedCrossRef Peintinger F, Buzdar AU, Kuerer HM et al (2008) Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Ann Oncol 19:2020–2025PubMedCrossRef
4.
Zurück zum Zitat Esteva FJ, Hortobagyi GN, Sahin AA et al (2001) Expression of erbB/HER receptors, heregulin and P38 in primary breast cancer using quantitative immunohistochemistry. Pathol Oncol Res 7:171–177PubMedCrossRef Esteva FJ, Hortobagyi GN, Sahin AA et al (2001) Expression of erbB/HER receptors, heregulin and P38 in primary breast cancer using quantitative immunohistochemistry. Pathol Oncol Res 7:171–177PubMedCrossRef
5.
Zurück zum Zitat Esteva FJ, Hortobagi GN (2004) Prognostic molecular markers in early breast cancer. Breast Cancer Res 6:109–118PubMedCrossRef Esteva FJ, Hortobagi GN (2004) Prognostic molecular markers in early breast cancer. Breast Cancer Res 6:109–118PubMedCrossRef
6.
Zurück zum Zitat Esteva FJ, Sahin AA, Cristofanilli M et al (2002) Molecular prognostic factors for breast cancer metastasis and survival. Semin Radiat Oncol 12:319–328PubMedCrossRef Esteva FJ, Sahin AA, Cristofanilli M et al (2002) Molecular prognostic factors for breast cancer metastasis and survival. Semin Radiat Oncol 12:319–328PubMedCrossRef
7.
Zurück zum Zitat Esteva FJ (2004) Monoclonal antibodies, small molecules, and vaccines in the treatment of breast cancer. Oncologist 9:4–9PubMedCrossRef Esteva FJ (2004) Monoclonal antibodies, small molecules, and vaccines in the treatment of breast cancer. Oncologist 9:4–9PubMedCrossRef
8.
Zurück zum Zitat Esteva FJ, Guo H, Zhang S et al (2010) PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 177:1647–1656PubMedCrossRef Esteva FJ, Guo H, Zhang S et al (2010) PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 177:1647–1656PubMedCrossRef
9.
Zurück zum Zitat Mazouni C, Hall A, Broglio K et al (2007) Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy. Cancer 109:496–501PubMedCrossRef Mazouni C, Hall A, Broglio K et al (2007) Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy. Cancer 109:496–501PubMedCrossRef
10.
Zurück zum Zitat Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672PubMedCrossRef Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672PubMedCrossRef
11.
Zurück zum Zitat Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684PubMedCrossRef Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684PubMedCrossRef
12.
Zurück zum Zitat Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283PubMedCrossRef Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283PubMedCrossRef
13.
Zurück zum Zitat Khatcheressian JL, Wolff AC, Smith TJ et al (2006) American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24:5091–5097PubMedCrossRef Khatcheressian JL, Wolff AC, Smith TJ et al (2006) American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24:5091–5097PubMedCrossRef
14.
Zurück zum Zitat Pintilie M (2006) Competing risks: a practical perspective. Wiley, Hoboken Pintilie M (2006) Competing risks: a practical perspective. Wiley, Hoboken
15.
Zurück zum Zitat Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 3:1141–1154CrossRef Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 3:1141–1154CrossRef
16.
Zurück zum Zitat Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef
17.
Zurück zum Zitat Park YH, Lee S, Cho EY et al (2010) Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status. Cancer Chemother Pharmacol 66:507–516PubMedCrossRef Park YH, Lee S, Cho EY et al (2010) Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status. Cancer Chemother Pharmacol 66:507–516PubMedCrossRef
18.
Zurück zum Zitat Kennecke H, Yerushalmi R, Woods R et al (2010) Metastatic behavior of breast cancer subtypes. J Clin Oncol 28:3271–3277PubMedCrossRef Kennecke H, Yerushalmi R, Woods R et al (2010) Metastatic behavior of breast cancer subtypes. J Clin Oncol 28:3271–3277PubMedCrossRef
19.
Zurück zum Zitat Smith I, Procter M, Gelber RD et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36PubMedCrossRef Smith I, Procter M, Gelber RD et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36PubMedCrossRef
20.
Zurück zum Zitat Vaz-Luis I, Ottesen RA, Hughes ME et al (2012) Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res 14:R129PubMedCrossRef Vaz-Luis I, Ottesen RA, Hughes ME et al (2012) Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res 14:R129PubMedCrossRef
21.
Zurück zum Zitat Arvold ND, Oh KS, Niemierko A et al. Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype. Breast Cancer Res Treat 2012 Arvold ND, Oh KS, Niemierko A et al. Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype. Breast Cancer Res Treat 2012
22.
23.
Zurück zum Zitat Yap YS, Cornelio GH, Devi BC et al (2012) Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer 107:1075–1082PubMedCrossRef Yap YS, Cornelio GH, Devi BC et al (2012) Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer 107:1075–1082PubMedCrossRef
24.
Zurück zum Zitat Musolino A, Ciccolallo L, Panebianco M et al (2011) Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study. Cancer 117:1837–1846PubMedCrossRef Musolino A, Ciccolallo L, Panebianco M et al (2011) Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study. Cancer 117:1837–1846PubMedCrossRef
25.
Zurück zum Zitat Heitz F, Rochon J, Harter P et al (2011) Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival. Ann Oncol 22:1571–1581PubMedCrossRef Heitz F, Rochon J, Harter P et al (2011) Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival. Ann Oncol 22:1571–1581PubMedCrossRef
26.
Zurück zum Zitat Niwinska A, Tacikowska M, Murawska M (2010) The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys 77:1134–1139PubMedCrossRef Niwinska A, Tacikowska M, Murawska M (2010) The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys 77:1134–1139PubMedCrossRef
27.
Zurück zum Zitat Duchnowska R, Dziadziuszko R, Czartoryska-Arlukowicz B et al (2009) Risk factors for brain relapse in HER2-positive metastatic breast cancer patients. Breast Cancer Res Treat 117:297–303PubMedCrossRef Duchnowska R, Dziadziuszko R, Czartoryska-Arlukowicz B et al (2009) Risk factors for brain relapse in HER2-positive metastatic breast cancer patients. Breast Cancer Res Treat 117:297–303PubMedCrossRef
28.
Zurück zum Zitat Heitz F, Harter P, Lueck HJ et al (2009) Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer 45:2792–2798PubMedCrossRef Heitz F, Harter P, Lueck HJ et al (2009) Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer 45:2792–2798PubMedCrossRef
29.
Zurück zum Zitat Pestalozzi BC, Zahrieh D, Price KN et al (2006) Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17:935–944PubMedCrossRef Pestalozzi BC, Zahrieh D, Price KN et al (2006) Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17:935–944PubMedCrossRef
30.
Zurück zum Zitat Bendell JC, Domchek SM, Burstein HJ et al (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977PubMedCrossRef Bendell JC, Domchek SM, Burstein HJ et al (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977PubMedCrossRef
31.
Zurück zum Zitat Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617PubMedCrossRef Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617PubMedCrossRef
32.
Zurück zum Zitat Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354PubMedCrossRef Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354PubMedCrossRef
33.
Zurück zum Zitat Dawood S, Broglio K, Esteva FJ et al (2009) Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol 20:621–627PubMedCrossRef Dawood S, Broglio K, Esteva FJ et al (2009) Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol 20:621–627PubMedCrossRef
34.
Zurück zum Zitat Leyland-Jones B (2009) Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol 27:5278–5286PubMedCrossRef Leyland-Jones B (2009) Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol 27:5278–5286PubMedCrossRef
35.
Zurück zum Zitat Bria E, Cuppone F, Fornier M et al (2008) Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Treat 109:231–239PubMedCrossRef Bria E, Cuppone F, Fornier M et al (2008) Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Treat 109:231–239PubMedCrossRef
36.
Zurück zum Zitat Gonzalez-Angulo AM, Cristofanilli M, Strom EA et al (2004) Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer 101:1760–1766PubMedCrossRef Gonzalez-Angulo AM, Cristofanilli M, Strom EA et al (2004) Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer 101:1760–1766PubMedCrossRef
37.
Zurück zum Zitat Slamon DJ, Leyland-Jones B, Shak S et al (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 et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef
38.
Zurück zum Zitat Esteva FJ, Valero V, Booser D et al (2002) Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 20:1800–1808PubMedCrossRef Esteva FJ, Valero V, Booser D et al (2002) Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 20:1800–1808PubMedCrossRef
39.
Zurück zum Zitat Fornier M, Esteva FJ, Seidman AD (2000) Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer. Semin Oncol 27:38–45PubMed Fornier M, Esteva FJ, Seidman AD (2000) Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer. Semin Oncol 27:38–45PubMed
40.
Zurück zum Zitat Morrow PK, Wulf GM, Ensor J et al (2011) Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 29:3126–3132PubMedCrossRef Morrow PK, Wulf GM, Ensor J et al (2011) Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 29:3126–3132PubMedCrossRef
41.
Zurück zum Zitat Morrow PK, Zambrana F, Esteva FJ (2009) Recent advances in systemic therapy: advances in systemic therapy for HER2-positive metastatic breast cancer. Breast Cancer Res 11:207PubMedCrossRef Morrow PK, Zambrana F, Esteva FJ (2009) Recent advances in systemic therapy: advances in systemic therapy for HER2-positive metastatic breast cancer. Breast Cancer Res 11:207PubMedCrossRef
42.
Zurück zum Zitat Esteva FJ, Hortobagyi GN (1999) Locally advanced breast cancer. Hematol Oncol Clin North Am 13:457–472PubMedCrossRef Esteva FJ, Hortobagyi GN (1999) Locally advanced breast cancer. Hematol Oncol Clin North Am 13:457–472PubMedCrossRef
43.
Zurück zum Zitat Dean-Colomb W, Esteva FJ. Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. Semin Oncol 2008; 35: S31–S38; quiz S40 Dean-Colomb W, Esteva FJ. Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. Semin Oncol 2008; 35: S31–S38; quiz S40
44.
Zurück zum Zitat Nahta R, Yuan LX, Du Y, Esteva FJ (2007) Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Mol Cancer Ther 6:667–674PubMedCrossRef Nahta R, Yuan LX, Du Y, Esteva FJ (2007) Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Mol Cancer Ther 6:667–674PubMedCrossRef
45.
Zurück zum Zitat Esteva FJ, Yu D, Hung MC, Hortobagyi GN (2010) Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 7:98–107PubMedCrossRef Esteva FJ, Yu D, Hung MC, Hortobagyi GN (2010) Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 7:98–107PubMedCrossRef
46.
Zurück zum Zitat Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743PubMedCrossRef Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743PubMedCrossRef
47.
Zurück zum Zitat Koboldt DC, Fulton RS, McLellan MD et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70CrossRef Koboldt DC, Fulton RS, McLellan MD et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70CrossRef
48.
Zurück zum Zitat Iwamoto T, Booser D, Valero V et al (2012) Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol 30:729–734PubMedCrossRef Iwamoto T, Booser D, Valero V et al (2012) Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol 30:729–734PubMedCrossRef
49.
Zurück zum Zitat Stephens PJ, Tarpey PS, Davies H et al (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486:400–404PubMed Stephens PJ, Tarpey PS, Davies H et al (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486:400–404PubMed
50.
Zurück zum Zitat Juul N, Szallasi Z, Eklund AC et al (2010) Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials. Lancet Oncol 11:358–365PubMedCrossRef Juul N, Szallasi Z, Eklund AC et al (2010) Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials. Lancet Oncol 11:358–365PubMedCrossRef
51.
Zurück zum Zitat Mittendorf EA, Wu Y, Scaltriti M et al (2009) Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 15:7381–7388PubMedCrossRef Mittendorf EA, Wu Y, Scaltriti M et al (2009) Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 15:7381–7388PubMedCrossRef
Metadaten
Titel
Effect of HER2 status on distant recurrence in early stage breast cancer
verfasst von
Kenneth R. Hess
Francisco J. Esteva
Publikationsdatum
01.01.2013
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2013
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2366-0

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