Abstract
We sought to compare the molecular signature of node negative cancers from two cohorts 15 years apart, to determine if there is molecular evidence of increase in low and ultralow risk cancers over time. We studied the impact of age, time period of diagnosis, and mammographic screening on biology of tumors where The Netherlands Cancer Institute 70-gene prognosis signature was generated as part of 2 validation series, one retrospective (1984–1992), Cohort 1, and one prospective (2004–2006), Cohort 2. A total of 866 patients were analyzed. Regardless of time period of diagnosis, the proportion of T1, grade 1, hormone receptor positive (HR) tumors, and good prognosis by 70-gene signature significantly increases as age increases (P < 0.01). In women aged 49–60, the time period of diagnosis significantly affects the proportion of cancers that were NKI 70-gene low risk: 40.6% (67/165) compared with 58% (119/205) for Cohorts 1 and 2, respectively. This is in contrast to the absence of a significant change for women under age 40, where 25% (17/68) and 30% (17/56) were low risk in Cohorts 1 and 2, respectively. In women aged 49–60, using an ultralow risk threshold of the 70-gene signature, 10% of tumors in Cohort 1 were ultralow risk compared with 30% for women with screen-detected cancers in Cohort 2. Older age and method of detection (screening) are associated with a higher likelihood of a biologically low risk tumor. In women over age 50, biologically low risk tumors are frequent and tools that classify risk may minimize overtreatment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Esserman L, Shieh Y, Thompson I (2009) Rethinking screening for breast cancer and prostate cancer. JAMA 302(15):1685–1692
Welch HG, Black WC (2010) Overdiagnosis in cancer. J Natl Cancer Inst 102(9):605–613
Ravdin PM et al (2001) Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19(4):980–991
Sorlie T et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874
Paik S et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826
van de Vijver MJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347(25):1999–2009
van’t Veer LJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
Buyse M et al (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98(17):1183–1192
Bueno-de-Mesquita JM et al (2007) Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol 8(12):1079–1087
Weigelt B et al (2003) Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci USA 100(26):15901–15905
Knauer M, Wenzl E, Rutgers EJ (2009) Gene expression profiling in breast cancer—design of a pooled database to address open questions. Eur Surg 41(5):221–227
Mook S et al (2009) The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol 21:717–722
Otten JD et al (2008) Impressive time-related influence of the Dutch screening programme on breast cancer incidence and mortality, 1975–2006. Int J Cancer 123(8):1929–1934
Weigelt B et al (2005) Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res 65(20):9155–9158
Hughes KS et al (2004) Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351(10):971–977
Sihto H et al (2008) Molecular subtypes of breast cancers detected in mammography screening and outside of screening. Clin Cancer Res 14(13):4103–4110
Berry DA et al (2009) Flawed inferences about screening mammography’s benefit based on observational data. J Clin Oncol 27(4):639–640; author reply 641–642
Chlebowski RT et al (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 289(24):3243–3253
Ravdin PM et al (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356(16):1670–1674
de Jong-van den Berg LTW, Faber A, van den Berg PB (2006) HRT use in 2001 and 2004 in The Netherlands—a world of difference. Maturitas 54(2):193–197
Mook S et al (2010) Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol 17:1406–1413
Berry DA (2008) The screening mammography paradox: better when found, perhaps better not to find. Br J Cancer 98(11):1729–1730
Esserman L, Thompson I (2010) Solving the over diagnosis dilemma. J Natl Cancer Inst 102(9):582–583
Zahl PH, Maehlen J, Welch HG (2008) The natural history of invasive breast cancers detected by screening mammography. Arch Intern Med 168(21):2311–2316
Acknowledgments
This study was supported by 5UO1CA111234 (Early Detection Research Network), the UCSF Dean’s Medical Student Summer Research Fellowship (YS) and the Dutch Genomics Initiative ‘Cancer Genomics Center’. The Dutch Association of Comprehensive Cancer Centers and Michiel Schaapveld are acknowledged for providing stage specific incidence data. The authors thank Karen Sepucha for editing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Esserman, L.J., Shieh, Y., Rutgers, E.J.T. et al. Impact of mammographic screening on the detection of good and poor prognosis breast cancers. Breast Cancer Res Treat 130, 725–734 (2011). https://doi.org/10.1007/s10549-011-1748-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-011-1748-z