Wolfson Institute of Preventive Medicine - Barts and The London

Long-term Anastrozole vs. Tamoxifen Treatment Effects (LATTE)

Centre for Cancer Prevention

Funding Body:  Cancer Research UK, AstraZeneca

Project Investigator:  Professor Jack Cuzick

Overview

Long-term Anastrozole vs. Tamoxifen Treatment Effects (LATTE) is the post ten-year follow up study of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant trial in postmenopausal women with early breast cancer.

The ATAC trial was a 10 year study designed to compare the efficacy and safety of Anastrozole and Tamoxifen Alone or in Combination, as treatment in post-menopausal women with invasive breast cancer.  There were approximately 9,500 patients included in the trial who received one of the following treatments for 5 years, and then off treatment for the remaining 5 years:

  • Anastrozole + Tamoxifen placebo
  • Tamoxifen + Anastrozole placebo
  • Anastrozole + Tamoxifen

Study Design

LATTE is the long-term follow-up study from the ATAC trial which occured over 10 years ago.  It includes approximately 4,300 post-menopausal women with breast cancer who were randomised to receive either Anastrozole + Tamoxifen placebo or Tamoxifen + Anastrozole placebo in the ATAC trial.

LATTE aims to provide additional efficacy data on breast cancer recurrence, information on survival, new primary cancers, major ischaemic cardiac and cerebrovascular events.

Treatments

There are no trial drugs or treatments associated with this observational study.

Objectives

To compare the ATAC patients randomised to receive Anastrozole to those randomised to receive Tamoxifen (and who have now all completed 5 years on trial therapy followed by 5 years off trial therapy).

Primary Objectives

  • Time to recurrence of breast cancer in the post 10 year period (defined as the earliest of local or distant recurrence, new primary breast cancer, or death)
  • Death after recurrence
Secondary Objectives
  • Cancer-specific survival
  • New breast primaries
  • Other cancers
  • Ischaemic cardiac and cerebrovascular events
  • Hip (and other) fractures

Inclusion Criteria

  • Post-menopausal women with breast cancer who were randomised to receive the mono-therapy arm (Anastrozole or Tamoxifen) in the ATAC trial
  • Not known to have died and alive after 10 years ATAC follow-up
  • Did not withdraw consent in the ATAC trial

Data Processing & Patient Confidentiality

Currently, sites choose to collect follow-up data using a variety of methods determined by local practice, aiming to do so on an annual basis. These include:

  • Routine clinic visit, based on local practice
  • By requesting information from GPs
  • Where appropriate, by post or telephone
  • From Hospital Tracking System

Queen Mary University of London will also collect information about LATTE study participants from NHS Digital, as well as other devolved public health bodies. This information will include participant name, date of birth, NHS number, and post code and health information, which is regarded as a special category of information. We will use these data to help assess the effectiveness of the trials’ interventions.

As Data Controller, Queen Mary University of London (QMUL) is responsible for the collection, storage and processing of these data for the study. These data include the following identifiable data, categorised under the General Data Protection Regulation (GDPR) as personal and sensitive:

  • Cancer incidence (any diagnosis of cancer and the type of cancer it is);;
  • Mortality data (in the event of death we will receive information confirming the date and cause of death);
  • Hospital Episode Statistics (HES) which utilises your in-patient, out-patient and A&E data (to look for other significant clinical events of interest to the clinical trial e.g. serious fractures, heart attacks);

The level of data collected from NHS/public health bodies will only be identifiable to us at QMUL and will not be shared with any third parties. Only authorised staff at the LATTE Coordinating Centre are able to access the data and only for specific purposes related to the trial. The data is stored in a secure, restricted-access environment. The data will be retained until destruction at the end of the study archiving period, which will be in 2039.

The legal bases for processing this data are exemption from Section 251 of the NHS Act 2006, as well as Article 6(1)(e) ‘performance of a task carried out in the public interest’ and Article 9(2)(j) ‘public interest, scientific or historical research purposes or statistical purposes’ pursuant to the GDPR.

As a University we use personally-identifiable information to conduct research to improve health, care and services. As a publicly-funded organisation, we have to ensure that it is in the public interest when we use personally-identifiable information from people who have agreed to take part in research. This means that when you agree to take part in a research study, we will use your data in the ways needed to conduct and analyse the research study. Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.

Health and care research should serve the public interest, which means that we have to demonstrate that our research serves the interests of society as a whole. We do this by following the UK Policy Framework for Health and Social Care Research.

If you wish to raise a complaint on how we have handled your personal data, you can contact our Data Protection Officer (data-protection@qmul.ac.uk) who will investigate the matter. If you are not satisfied with our response or believe we are processing your personal data in a way that is not lawful you can complain to the Information Commissioner’s Office (ICO).

Should you have any further questions about the study, please contact the LATTE Central Coordinating Office for more detail on how to withdraw from further data collection as part of the LATTE study, by calling 020 7882 5973, e-mailing latte@qmul.ac.uk or contacting their LATTE study site.

Additional Information

Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M (2008). Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol., 9(1):45-53.

 

The ATAC Trialists' Group (2003) (includes J Cuzick, Independent Statistician). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer - Results of the ATAC (arimidex, tamoxifen alone or in combination) trial efficacy and safety update analysis. Cancer, 98: 1802-1810.

 

The ATAC Trialists' Group: Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, Houghton J, Locker GY, Nabholtz JM (2006). Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol. Aug; 7(8):633-43.

 

Baum M, Budzar AU, Cuzick J, et al (2002). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet, 359: 2131-2139.

 

Cuzick, J. (2015). Statistical controversies in clinical research: long-term follow-up of clinical trials in cancer. Annals of Oncology26(12), 2363–2366. http://doi.org/10.1093/annonc/mdv392

 

Cuzick J, Sestak I, Cella D, Fallowfield L; on behalf of the ATAC Trialists' Group (2008). Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol., 9(12):1143-1148.

 

Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, on behalf of the ATAC/LATTE investigators (2010). Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Onc., 11(12):1109-10.

  

Cuzick, J., M. Dowsett, S. Pineda, C. Wale, J. Salter, E. Quinn, L. Zabaglo, E. Mallon, A. R. Green, I. O. Ellis, A. Howell, A. U. Buzdar and J. F. Forbes (2011). Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer. Journal of Clinical Oncology 29(32): 4273-4278.

 

Eastell R, Adams J, Clack G, Howell A, Cuzick J, Mackey J, Beckmann MW, Coleman RE (2011). Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol. 2011 Apr;22(4):857-62

 

Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008). Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol, 26(7):1051-7.

 

Eastell R, Hannon R, Cuzick J, Dowsett M, Clack G, Adams J (2006) on behalf of ATAC Trialists Group. Effect of an Aromatase Inhibitor on BMD and Bone Turnover Markers: 2-year Results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) Trial. Journal of Bone and Mineral Research, Vol 21:8, 1215-1223.

 

Gnant, M., I. Sestak, M. Filipits, M. Dowsett, M. Balic, E. Lopez-Knowles, R. Greil, P. Dubsky, H. Stoeger, M. Rudas, R. Jakesz, S. Ferree, J. W. Cowens, T. Nielsen, C. Schaper, C. Fesl and J. Cuzick (2015). Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype. Ann Oncol 26(8): 1685-1691.

 

Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group (2005). Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet, 365: 60-2. (Correspondence, Lancet, 365: 1225-1226).

Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, et al.(2015) Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: A Combined Analysis of Patients From the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination Randomized Trials Using the PAM50 Risk of Recurrence Score. J Clin Oncol., 33(8):916-22. 

Sestak I, Sapunar F, Cuzick J (2009). Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol., 27(30):4961-5.