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

Breast cancer is increasingly becoming a “survivable” disease, and an increasing number of recurrences occur late, so that there is much interest about the long-term efficacy and safety of treatments. The Oxford Overview process has provided useful data on follow-up for 15-20 years after tamoxifen therapy. Such data are lacking for the newer aromatase inhibitors (AIs). This study provides a unique opportunity to address this issue. The ‘Anastrazole, Tamoxifen, Alone or in Combination’ (ATAC) trial is the vanguard breast cancer trial for the use of AIs in the adjuvant setting, with a median follow-up of 100 months.

Established in 2010, the Long-term Anastrozole vs Tamoxifen Treatment Effects (LATTE) observational study aims to collect vital long-term safety and efficacy data on anastrozole and tamoxifen, drugs that were taken by post-menopausal women as part of the Anastrozole Tamoxifen Alone or in Combination (ATAC) trial. ATAC was a crucial breast cancer trial evaluating the use of aromatase inhibitors (AIs) in the adjuvant setting, with a median follow-up of over 10 years. The ATAC trial assessed the safety and efficacy of anastrozole+placebo, tamoxifen+placebo and anastrozole+tamoxifen in post-menopausal women undergoing treatment for invasive primary breast cancer.

The LATTE study aims to collect further follow-up information on a maximum of 2200 UK eligible patients, who were randomised to the monotherapy arms (anastrozole or tamoxifen) in the ATAC trial. The cohort was reduced from 4,300 to 2,145 due to patients either passing away or the study losing contact with them and a cohort of 1466 out of 2145 was flagged by NHS England. The study’s primary objective is to provide additional efficacy and safety data on time to recurrence of breast cancer and death after recurrence. The secondary objectives include time to distant recurrence, cancer-specific survival, new breast primaries, other cancers, ischaemic cardiac and cerebrovascular events and hip (and other) fractures. Participants will be followed-up annually until at least 15 years median follow-up.

It should be noted that the Research Ethics Committee (REC) and Confidentiality Advisory Group (CAG) have already approved the LATTE study for collection of vital HES, cancer registration and mortality data sets as part of this study. The study is funded by AstraZeneca. A five year extension has been approved by the Ethics Committee to extend the study; following up of data, until 1st March 2024.

In 2010, results from 10-year follow-up from ATAC demonstrated that there is long-term superiority of anastrozole over tamoxifen as initial adjuvant therapy for post-menopausal women with hormone-sensitive early breast cancer. This paper demonstrated that there were significantly lower rates of local and distant recurrence, as well as reduced contralateral breast cancer in patients treated with anastrozole. (Cuzick, Sestak et al, Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer, Lancet Oncol, 2010 11(12): 1135-41). However, in 2016 a recent preliminary analysis of the LATTE study demonstrated that the benefits of anastrozole do not continue long-term after 10 years in terms of reduced recurrence rates. The results also suggested that there was a larger reduction of new contralateral tumours with tamoxifen. However, the preliminary analysis was partial in that there was limited data with possible under reporting of vital events linked to the safety and efficacy endpoints; this therefore may diminish the effect of anastrozole. Queen Mary University of London (QMUL) - acting as data controller who also processes data - therefore require extended cohort events, obtainable from HES, cancer registration and mortality data in order to conclude the long-term safety of either intervention. QMUL will then be able to integrate the pseudonymised LATTE data with the ATAC data sets in order to perform an analysis of the overall 20-year follow-up period.

LATTE patients are originally from the ATAC study and the aim of the LATTE study is to follow up these patients who had received trial treatment on the ATAC trial. The LATTE study comprises of the original ATAC patients who have either not withdrawn consent and are still alive. The datasets received from NHS England will be appended to the initial datasets from the ATAC study, where we plan to conduct a full outcome analysis of the patients on the LATTE study. This updated analysis will be published in 2020. The following up of the LATTE patients through collection of digital data sets will be an ongoing process over time.

AstraZeneca have funded LATTE when they were collecting data from sites but all the sites are now closed and QMUL are only collecting data from NHS England. AstraZeneca are not involved with any data analysis nor do they receive any data from QMUL’s analysis. Nothing is sent to AstraZeneca except for milestone updates such as dates of publications. This study has no commercial element and AstraZeneca don’t have any influence over the results either. QMUL have received a 5 year extension from AstraZeneca for funding which supports the follow up phases via collection of lifetime follow-up data from NHS England.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This study is in the interest of the public as it aims to show the long term effects of Anastrozole vs Tamoxifen Treatment follow breast cancer treatment.

Data from a preliminary analysis was presented at the San Antonio Breast Cancer Symposium in December 2016 as a poster. QMUL had planed to publish the main results from the LATTE cohort within 12-18 months after receipt of the NHS England data. However, this was delayed due to Covid and they are now working on it. This will enable them to report a more complete data set, with up-to-date information on recurrences, deaths, other primary cancers, and adverse events. To demonstrate a potential carry-over effect of anastrozole versus tamoxifen, long-term follow-up in excess of 10 years is essential. Therefore, after the initial publication QMUL plan to publish an updated manuscript on the benefits of AI therapy in 2024/2025. The main target audience for their data outputs are the patients with early breast cancer, and the medical professionals who can use the results for decision making.

Further outputs and analyses of the LATTE study will be published in peer-reviewed medical journals such as The Lancet, The Lancet Oncology, Breast Cancer Research and Treatment and the British Journal of Cancer. Outputs are expected in 2023/24 when there is over 10 years of follow-up data available.

The public will be made aware of the research progress through the following web page: https://www.qmul.ac.uk/wolfson/research-projects/current-projects/projects/latte-study.html.

In 2020 the public and patient involvement event was hosted to collaboratively discuss with breast cancer research participants, their views on the study procedures specifically relating to collection of identifiable data for use in future analyses. During the event, talks and presentations were held which discussed the findings from the analyses conducted so far and an open discussion on how participants felt about the study procedures specifically on long term follow up data collection. There was a positive response to the event where patients felt happy to be included and their data to be collected as described in the study protocol and used for future analyses. Patients commented on that it is most appropriate to conduct such analyses with the use of long term follow up data as it could help to streamline treatment options and the benefits and side effects of treatment options in the future. The study also made sure to highlight that under no circumstances identifiable data would be released to a third party and that all data will always remain in a secure and locked environment.

Outputs will be published in peer-reviewed journals like Lancet Journal of Clinical Oncology or Breast Cancer Research and Treatment.

The anticipated audiences of the above outputs are researchers, scientists, stakeholders for the wider project and research participants.

Policy makers and public health bodies such as NICE will be targeted with the outputs of the study. NICE will be advised on the long-term safety and efficacy of tamoxifen and anastrozole as adjuvant therapy. These analyses will enable patients and women who have been diagnosed with invasive breast cancer to make a more informed decision on the adjuvant treatment options available to them.

Data contained in any outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

The funder will not have influence on the outcomes nor suppress any of the findings of the research.

Registry data provided to date has identified numerous cases of breast cancers, other cancers and the effects of long term treatment in participants within the LATTE cohort, with whom the Centre for Cancer Prevention at Queen Mary University of London have no direct contact and therefore are not already known by the study team. Collection of this data has contributed directly to the primary endpoints of the trial, providing us with information on mortality and recurrence of breast cancer.

The ATAC trial which is the vanguard breast cancer trial for the use of AI's in the adjuvant setting, with a median follow up of 10 years. The LATTE study proposes to collect further follow up information on as many eligible participants as possible who were randomised to monotherapy (anastrozole or tamoxifen). The results of the main analysis of the ATAC trial have formed the basis for the decision by the National Institute for Health and Care Excellence (NICE) to include anastrozole in their guidelines, recommending anastrozole as a first line treatment for post-menopausal women with early stage breast cancer. The continuing follow-up in the LATTE study will enhance our understanding on long term effects of anastrozole and tamoxifen in terms of secondary prevention and late adverse events. These data will help to further understand who benefits the most from taking these drugs and hence will form evidence for clinical/oncological decision making.

Breast cancer is increasingly becoming a “survivable” disease, and an increasing number of recurrences occur late, so that there is much interest about the long-term efficacy and safety of treatments. The Oxford Overview process has provided useful data on follow-up for 15-20 years after tamoxifen therapy. Such data are lacking for the newer aromatase inhibitors (AIs). This study provides a unique opportunity to address this issue. The ‘Anastrazole, Tamoxifen, Alone or in Combination’ (ATAC) trial is the vanguard breast cancer trial for the use of AIs in the adjuvant setting, with a median follow-up of 100 months.

Established in 2010, the Long-term Anastrozole vs Tamoxifen Treatment Effects (LATTE) observational study aims to collect vital long-term safety and efficacy data on anastrozole and tamoxifen, drugs that were taken by post-menopausal women as part of the Anastrozole Tamoxifen Alone or in Combination (ATAC) trial. ATAC was a crucial breast cancer trial evaluating the use of aromatase inhibitors (AIs) in the adjuvant setting, with a median follow-up of over 10 years. The ATAC trial assessed the safety and efficacy of anastrozole+placebo, tamoxifen+placebo and anastrozole+tamoxifen in post-menopausal women undergoing treatment for invasive primary breast cancer.

The LATTE study aims to collect further follow-up information on a maximum of 2200 UK eligible patients, who were randomised to the monotherapy arms (anastrozole or tamoxifen) in the ATAC trial. The cohort was reduced from 4,300 to 2,145 due to patients either passing away or the study losing contact with them and a cohort of 1466 out of 2145 was flagged by NHS Digital. The study’s primary objective is to provide additional efficacy and safety data on time to recurrence of breast cancer and death after recurrence. The secondary objectives include time to distant recurrence, cancer-specific survival, new breast primaries, other cancers, ischaemic cardiac and cerebrovascular events and hip (and other) fractures. Participants will be followed-up annually until at least 15 years median follow-up.

It should be noted that the Research Ethics Committee (REC) and Confidentiality Advisory Group (CAG) have already approved the LATTE study for collection of vital HES, cancer registration and mortality data sets as part of this study. The study is funded by AstraZeneca. A five year extension has been approved by the Ethics Committee to extend the study; following up of data, until 1st March 2024.

In 2010, results from 10-year follow-up from ATAC demonstrated that there is long-term superiority of anastrozole over tamoxifen as initial adjuvant therapy for post-menopausal women with hormone-sensitive early breast cancer. This paper demonstrated that there were significantly lower rates of local and distant recurrence, as well as reduced contralateral breast cancer in patients treated with anastrozole. (Cuzick, Sestak et al, Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer, Lancet Oncol, 2010 11(12): 1135-41). However, in 2016 a recent preliminary analysis of the LATTE study demonstrated that the benefits of anastrozole do not continue long-term after 10 years in terms of reduced recurrence rates. The results also suggested that there was a larger reduction of new contralateral tumours with tamoxifen. However, the preliminary analysis was partial in that there was limited data with possible under reporting of vital events linked to the safety and efficacy endpoints; this therefore may diminish the effect of anastrozole. Queen Mary University of London (QMUL) - acting as data controller who also processes data - therefore require extended cohort events, obtainable from HES, cancer registration and mortality data in order to conclude the long-term safety of either intervention. QMUL will then be able to integrate the pseudonymised LATTE data with the ATAC data sets in order to perform an analysis of the overall 20-year follow-up period.

LATTE patients are originally from the ATAC study and the aim of the LATTE study is to follow up these patients who had received trial treatment on the ATAC trial. The LATTE study comprises of the original ATAC patients who have either not withdrawn consent and are still alive. The datasets received from NHS Digital will be appended to the initial datasets from the ATAC study, where we plan to conduct a full outcome analysis of the patients on the LATTE study. This updated analysis will be published in 2020. The following up of the LATTE patients through collection of digital data sets will be an ongoing process over time.

AstraZeneca have funded LATTE when they were collecting data from sites but all the sites are now closed and QMUL are only collecting data from NHS Digital. AstraZeneca are not involved with any data analysis nor do they receive any data from QMUL’s analysis. Nothing is sent to AstraZeneca except for milestone updates such as dates of publications. This study has no commercial element and AstraZeneca don’t have any influence over the results either. QMUL have received a 5 year extension from AstraZeneca for funding which supports the follow up phases via collection of lifetime follow-up data from NHS Digital.

The legal basis under GDPR:

Article 6(1)(e): processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

Article 9(2)(j): Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This study is in the interest of the public as it aims to show the long term effects of Anastrozole vs Tamoxifen Treatment follow breast cancer treatment.

Data from a preliminary analysis was presented at the San Antonio Breast Cancer Symposium in December 2016 as a poster. QMUL had planed to publish the main results from the LATTE cohort within 12-18 months after receipt of the NHS Digital data. However, this was delayed due to Covid and they are now working on it. This will enable them to report a more complete data set, with up-to-date information on recurrences, deaths, other primary cancers, and adverse events. To demonstrate a potential carry-over effect of anastrozole versus tamoxifen, long-term follow-up in excess of 10 years is essential. Therefore, after the initial publication QMUL plan to publish an updated manuscript on the benefits of AI therapy in 2024/2025. The main target audience for their data outputs are the patients with early breast cancer, and the medical professionals who can use the results for decision making.

Further outputs and analyses of the LATTE study will be published in peer-reviewed medical journals such as The Lancet, The Lancet Oncology, Breast Cancer Research and Treatment and the British Journal of Cancer. Outputs are expected in 2023/24 when there is over 10 years of follow-up data available.

The public will be made aware of the research progress through the following web page: https://www.qmul.ac.uk/wolfson/research-projects/current-projects/projects/latte-study.html.

In 2020 the public and patient involvement event was hosted to collaboratively discuss with breast cancer research participants, their views on the study procedures specifically relating to collection of identifiable data for use in future analyses. During the event, talks and presentations were held which discussed the findings from the analyses conducted so far and an open discussion on how participants felt about the study procedures specifically on long term follow up data collection. There was a positive response to the event where patients felt happy to be included and their data to be collected as described in the study protocol and used for future analyses. Patients commented on that it is most appropriate to conduct such analyses with the use of long term follow up data as it could help to streamline treatment options and the benefits and side effects of treatment options in the future. The study also made sure to highlight that under no circumstances identifiable data would be released to a third party and that all data will always remain in a secure and locked environment.

Outputs will be published in peer-reviewed journals like Lancet Journal of Clinical Oncology or Breast Cancer Research and Treatment.

The anticipated audiences of the above outputs are researchers, scientists, stakeholders for the wider project and research participants.

Policy makers and public health bodies such as NICE will be targeted with the outputs of the study. NICE will be advised on the long-term safety and efficacy of tamoxifen and anastrozole as adjuvant therapy. These analyses will enable patients and women who have been diagnosed with invasive breast cancer to make a more informed decision on the adjuvant treatment options available to them.

Data contained in any outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

The funder will not have influence on the outcomes nor suppress any of the findings of the research.

Registry data provided to date has identified numerous cases of breast cancers, other cancers and the effects of long term treatment in participants within the LATTE cohort, with whom the Centre for Cancer Prevention at Queen Mary University of London have no direct contact and therefore are not already known by the study team. Collection of this data has contributed directly to the primary endpoints of the trial, providing us with information on mortality and recurrence of breast cancer.

The ATAC trial which is the vanguard breast cancer trial for the use of AI's in the adjuvant setting, with a median follow up of 10 years. The LATTE study proposes to collect further follow up information on as many eligible participants as possible who were randomised to monotherapy (anastrozole or tamoxifen). The results of the main analysis of the ATAC trial have formed the basis for the decision by the National Institute for Health and Care Excellence (NICE) to include anastrozole in their guidelines, recommending anastrozole as a first line treatment for post-menopausal women with early stage breast cancer. The continuing follow-up in the LATTE study will enhance our understanding on long term effects of anastrozole and tamoxifen in terms of secondary prevention and late adverse events. These data will help to further understand who benefits the most from taking these drugs and hence will form evidence for clinical/oncological decision making.

Breast cancer is increasingly becoming a “survivable” disease, and an increasing number of recurrences occur late, so that there is much interest about the long-term efficacy and safety of treatments. The Oxford Overview process has provided useful data on follow-up for 15-20 years after tamoxifen therapy. Such data are lacking for the newer aromatase inhibitors (AIs). This study provides a unique opportunity to address this issue. The ‘Anastrazole, Tamoxifen, Alone or in Combination’ (ATAC) trial is the vanguard breast cancer trial for the use of AIs in the adjuvant setting, with a median follow-up of 100 months.

Established in 2010, the Long-term Anastrozole vs Tamoxifen Treatment Effects (LATTE) observational study aims to collect vital long-term safety and efficacy data on anastrozole and tamoxifen, drugs that were taken by post-menopausal women as part of the Anastrozole Tamoxifen Alone or in Combination (ATAC) trial. ATAC was a crucial breast cancer trial evaluating the use of aromatase inhibitors (AIs) in the adjuvant setting, with a median follow-up of over 10 years. The ATAC trial assessed the safety and efficacy of anastrozole+placebo, tamoxifen+placebo and anastrozole+tamoxifen in post-menopausal women undergoing treatment for invasive primary breast cancer.

The LATTE study aims to collect further follow-up information on a maximum of 2200 UK eligible patients, who were randomised to the monotherapy arms (anastrozole or tamoxifen) in the ATAC trial. The cohort was reduced from 4,300 to 2,200 due to patients either passing away or the study losing contact with them. The study’s primary objective is to provide additional efficacy and safety data on time to recurrence of breast cancer and death after recurrence. The secondary objectives include time to distant recurrence, cancer-specific survival, new breast primaries, other cancers, ischaemic cardiac and cerebrovascular events and hip (and other) fractures. Participants will be followed-up annually until at least 15 years median follow-up.

It should be noted that the Research Ethics Committee (REC) and Confidentiality Advisory Group (CAG) have already approved the LATTE study for collection of vital HES, cancer registration and mortality data sets as part of this study. The study is funded by AstraZeneca. A five year extension has been approved by the Ethics Committee to extend the study; following up of data, until 1st March 2024.

In 2010, results from 10-year follow-up from ATAC demonstrated that there is long-term superiority of anastrozole over tamoxifen as initial adjuvant therapy for post-menopausal women with hormone-sensitive early breast cancer. This paper demonstrated that there were significantly lower rates of local and distant recurrence, as well as reduced contralateral breast cancer in patients treated with anastrozole. (Cuzick, Sestak et al, Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer, Lancet Oncol, 2010 11(12): 1135-41). However, in 2016 a recent preliminary analysis of the LATTE study demonstrated that the benefits of anastrozole do not continue long-term after 10 years in terms of reduced recurrence rates. The results also suggested that there was a larger reduction of new contralateral tumours with tamoxifen. However, the preliminary analysis was partial in that there was limited data with possible under reporting of vital events linked to the safety and efficacy endpoints; this therefore may diminish the effect of anastrozole. Queen Mary University of London (QMUL) - acting as data controller who also processes data - therefore require extended cohort events, obtainable from HES, cancer registration and mortality data in order to conclude the long-term safety of either intervention. QMUL will then be able to integrate the pseudonymised LATTE data with the ATAC data sets in order to perform an analysis of the overall 20-year follow-up period.

LATTE patients are originally from the ATAC study and the aim of the LATTE study is to follow up these patients who had received trial treatment on the ATAC trial. The LATTE study comprises of the original ATAC patients who have either not withdrawn consent and are still alive. The datasets received from NHS Digital will be appended to the initial datasets from the ATAC study, where we plan to conduct a full outcome analysis of the patients on the LATTE study. This updated analysis will be published in 2020. The following up of the LATTE patients through collection of digital data sets will be an ongoing process over time.

The legal basis under GDPR:

Article 6(1)(e): processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

Article 9(2)(j): Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

Data from a preliminary analysis was presented at the San Antonio Breast Cancer Symposium in December 2016 as a poster. QMUL plan to publish the main results from the LATTE cohort within 12-18 months after receipt of the NHS Digital data. This will enable them to report a more complete data set, with up-to-date information on recurrences, deaths, other primary cancers, and adverse events. To demonstrate a potential carry-over effect of anastrozole versus tamoxifen, long-term follow-up in excess of 10 years is essential. Therefore, after the initial publication in approximately 2020 QMUL plan to publish an updated manuscript on the benefits of AI therapy in 2022/2023. The main target audience for their data outputs are the patients with early breast cancer, and the medical professionals who can use the results for decision making.

Further outputs and analyses of the LATTE study will be published in peer-reviewed medical journals such as The Lancet, The Lancet Oncology, Breast Cancer Research and Treatment and the British Journal of Cancer. Outputs are expected in 2020 when there is 10 years of follow-up data available.

The public will be made aware of the research progress through the following web page: https://www.qmul.ac.uk/wolfson/research-projects/current-projects/projects/latte-study.html.

Recently a public and patient involvement event was hosted to collaboratively discuss with breast cancer research participants, their views on the study procedures specifically relating to collection of identifiable data for use in future analyses. During the event, talks and presentations were held which discussed the findings from the analyses conducted so far and an open discussion on how participants felt about the study procedures specifically on long term follow up data collection. There was a positive response to the event where patients felt happy to be included and their data to be collected as described in the study protocol and used for future analyses. Patients commented on that it is most appropriate to conduct such analyses with the use of long term follow up data as it could help to streamline treatment options and the benefits and side effects of treatment options in the future. The study also made sure to highlight that under no circumstances identifiable data would be released to a third party and that all data will always remain in a secure and locked environment.

Outputs will be published in peer-reviewed journals like Lancet Journal of Clinical Oncology or Breast Cancer Research and Treatment.

The anticipated audiences of the above outputs are researchers, scientists, stakeholders for the wider project and research participants.

Policy makers and public health bodies such as NICE will be targeted with the outputs of the study. NICE will be advised on the long-term safety and efficacy of tamoxifen and anastrozole as adjuvant therapy. These analyses will enable patients and women who have been diagnosed with invasive breast cancer to make a more informed decision on the adjuvant treatment options available to them.

Data contained in any outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

The funder will not have influence on the outcomes nor suppress any of the findings of the research.

Registry data provided to date has identified numerous cases of breast cancers, other cancers and the effects of long term treatment in participants within the LATTE cohort, with whom the Centre for Cancer Prevention at Queen Mary University of London have no direct contact and therefore are not already known by the study team. Collection of this data has contributed directly to the primary endpoints of the trial, providing us with information on mortality and recurrence of breast cancer.

The ATAC trial which is the vanguard breast cancer trial for the use of AI's in the adjuvant setting, with a median follow up of 10 years. The LATTE study proposes to collect further follow up information on as many eligible participants as possible who were randomised to monotherapy (anastrozole or tamoxifen). The results of the main analysis of the ATAC trial have formed the basis for the decision by the National Institute for Health and Care Excellence (NICE) to include anastrozole in their guidelines, recommending anastrozole as a first line treatment for post-menopausal women with early stage breast cancer. The continuing follow-up in the LATTE study will enhance our understanding on long term effects of anastrozole and tamoxifen in terms of secondary prevention and late adverse events. These data will help to further understand who benefits the most from taking these drugs and hence will form evidence for clinical/oncological decision making.

Breast cancer is increasingly becoming a “survivable” disease, and an increasing number of recurrences occur late, so that there is much interest about the long-term efficacy and safety of treatments. The Oxford Overview process has provided useful data on follow-up for 15-20 years after tamoxifen therapy. Such data are lacking for the newer aromatase inhibitors (AIs). This study provides a unique opportunity to address this issue. The ‘Anastrazole, Tamoxifen, Alone or in Combination’ (ATAC) trial is the vanguard breast cancer trial for the use of AIs in the adjuvant setting, with a median follow-up of 100 months.

Established in 2010, the Long-term Anastrozole vs Tamoxifen Treatment Effects (LATTE) observational study aims to collect vital long-term safety and efficacy data on anastrozole and tamoxifen, drugs that were taken by post-menopausal women as part of the Anastrozole Tamoxifen Alone or in Combination (ATAC) trial. ATAC was a crucial breast cancer trial evaluating the use of aromatase inhibitors (AIs) in the adjuvant setting, with a median follow-up of over 10 years. The ATAC trial assessed the safety and efficacy of anastrozole+placebo, tamoxifen+placebo and anastrozole+tamoxifen in post-menopausal women undergoing treatment for invasive primary breast cancer.

The LATTE study aims to collect further follow-up information on a maximum of 2200 UK eligible patients, who were randomised to the monotherapy arms (anastrozole or tamoxifen) in the ATAC trial. The cohort was reduced from 4,300 to 2,200 due to patients either passing away or the study losing contact with them. The study’s primary objective is to provide additional efficacy and safety data on time to recurrence of breast cancer and death after recurrence. The secondary objectives include time to distant recurrence, cancer-specific survival, new breast primaries, other cancers, ischaemic cardiac and cerebrovascular events and hip (and other) fractures. Participants will be followed-up annually until at least 15 years median follow-up.

It should be noted that the Research Ethics Committee (REC) and Confidentiality Advisory Group (CAG) have already approved the LATTE study for collection of vital HES, cancer registration and mortality data sets as part of this study. The study is funded by AstraZeneca. A five year extension has been approved by the Ethics Committee to extend the study; following up of data, until 1st March 2024.

In 2010, results from 10-year follow-up from ATAC demonstrated that there is long-term superiority of anastrozole over tamoxifen as initial adjuvant therapy for post-menopausal women with hormone-sensitive early breast cancer. This paper demonstrated that there were significantly lower rates of local and distant recurrence, as well as reduced contralateral breast cancer in patients treated with anastrozole. (Cuzick, Sestak et al, Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer, Lancet Oncol, 2010 11(12): 1135-41). However, in 2016 a recent preliminary analysis of the LATTE study demonstrated that the benefits of anastrozole do not continue long-term after 10 years in terms of reduced recurrence rates. The results also suggested that there was a larger reduction of new contralateral tumours with tamoxifen. However, the preliminary analysis was partial in that there was limited data with possible under reporting of vital events linked to the safety and efficacy endpoints; this therefore may diminish the effect of anastrozole. Queen Mary University of London (QMUL) - acting as data controller who also processes data - therefore require extended cohort events, obtainable from HES, cancer registration and mortality data in order to conclude the long-term safety of either intervention. QMUL will then be able to integrate the pseudonymised LATTE data with the ATAC data sets in order to perform an analysis of the overall 20-year follow-up period.

LATTE patients are originally from the ATAC study and the aim of the LATTE study is to follow up these patients who had received trial treatment on the ATAC trial. The LATTE study comprises of the original ATAC patients who have either not withdrawn consent and are still alive. The datasets received from NHS Digital will be appended to the initial datasets from the ATAC study, where we plan to conduct a full outcome analysis of the patients on the LATTE study. This updated analysis will be published in 2020. The following up of the LATTE patients through collection of digital data sets will be an ongoing process over time.

The legal basis under GDPR:

Article 6(1)(e): processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

Article 9(2)(j): Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

Data from a preliminary analysis was presented at the San Antonio Breast Cancer Symposium in December 2016 as a poster. QMUL plan to publish the main results from the LATTE cohort within 12-18 months after receipt of the NHS Digital data. This will enable them to report a more complete data set, with up-to-date information on recurrences, deaths, other primary cancers, and adverse events. To demonstrate a potential carry-over effect of anastrozole versus tamoxifen, long-term follow-up in excess of 10 years is essential. Therefore, after the initial publication in approximately 2020 QMUL plan to publish an updated manuscript on the benefits of AI therapy in 2022/2023. The main target audience for their data outputs are the patients with early breast cancer, and the medical professionals who can use the results for decision making.

Further outputs and analyses of the LATTE study will be published in peer-reviewed medical journals such as The Lancet, The Lancet Oncology, Breast Cancer Research and Treatment and the British Journal of Cancer. Outputs are expected in 2020 when there is 10 years of follow-up data available.

The public will be made aware of the research progress through the following web page: https://www.qmul.ac.uk/wolfson/research-projects/current-projects/projects/latte-study.html.

Recently a public and patient involvement event was hosted to collaboratively discuss with breast cancer research participants, their views on the study procedures specifically relating to collection of identifiable data for use in future analyses. During the event, talks and presentations were held which discussed the findings from the analyses conducted so far and an open discussion on how participants felt about the study procedures specifically on long term follow up data collection. There was a positive response to the event where patients felt happy to be included and their data to be collected as described in the study protocol and used for future analyses. Patients commented on that it is most appropriate to conduct such analyses with the use of long term follow up data as it could help to streamline treatment options and the benefits and side effects of treatment options in the future. The study also made sure to highlight that under no circumstances identifiable data would be released to a third party and that all data will always remain in a secure and locked environment.

Outputs will be published in peer-reviewed journals like Lancet Journal of Clinical Oncology or Breast Cancer Research and Treatment.

The anticipated audiences of the above outputs are researchers, scientists, stakeholders for the wider project and research participants.

Policy makers and public health bodies such as NICE will be targeted with the outputs of the study. NICE will be advised on the long-term safety and efficacy of tamoxifen and anastrozole as adjuvant therapy. These analyses will enable patients and women who have been diagnosed with invasive breast cancer to make a more informed decision on the adjuvant treatment options available to them.

Data contained in any outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

The funder will not have influence on the outcomes nor suppress any of the findings of the research.

Registry data provided to date has identified numerous cases of breast cancers, other cancers and the effects of long term treatment in participants within the LATTE cohort, with whom the Centre for Cancer Prevention at Queen Mary University of London have no direct contact and therefore are not already known by the study team. Collection of this data has contributed directly to the primary endpoints of the trial, providing us with information on mortality and recurrence of breast cancer.

The ATAC trial which is the vanguard breast cancer trial for the use of AI's in the adjuvant setting, with a median follow up of 10 years. The LATTE study proposes to collect further follow up information on as many eligible participants as possible who were randomised to monotherapy (anastrozole or tamoxifen). The results of the main analysis of the ATAC trial have formed the basis for the decision by the National Institute for Health and Care Excellence (NICE) to include anastrozole in their guidelines, recommending anastrozole as a first line treatment for post-menopausal women with early stage breast cancer. The continuing follow-up in the LATTE study will enhance our understanding on long term effects of anastrozole and tamoxifen in terms of secondary prevention and late adverse events. These data will help to further understand who benefits the most from taking these drugs and hence will form evidence for clinical/oncological decision making.

Breast cancer is increasingly becoming a “survivable” disease, and an increasing number of recurrences occur late, so that there is much interest about the long-term efficacy and safety of treatments. The Oxford Overview process has provided useful data on follow-up for 15-20 years after tamoxifen therapy. Such data are lacking for the newer aromatase inhibitors (AIs). This study provides a unique opportunity to address this issue. The ‘Arimidex, Tamoxifen, Alone or in Combination’ (ATAC) trial is the vanguard breast cancer trial for the use of AIs in the adjuvant setting, with a median follow-up of 100 months.

Established in 2010, the Long-term Anastrozole vs Tamoxifen Treatment Effects (LATTE) observational study aims to collect vital long-term safety and efficacy data on anastrozole and tamoxifen, drugs that were taken by post-menopausal women as part of the Anastrozole Tamoxifen Alone or in Combination (ATAC) trial. ATAC was a crucial breast cancer trial evaluating the use of aromatase inhibitors (AIs) in the adjuvant setting, with a median follow-up of over 10 years. The ATAC trial assessed the safety and efficacy of anastrozole+placebo, tamoxifen+placebo and anastrozole+tamoxifen in post-menopausal women undergoing treatment for invasive primary breast cancer

The LATTE study aims to collect further follow-up information on a maximum of 2200 UK eligible patients, who were randomised to the monotherapy arms (anastrozole or tamoxifen) in the ATAC trial. The study’s primary objective is to provide additional efficacy and safety data on time to recurrence of breast cancer and death after recurrence. The secondary objectives include time to distant recurrence, cancer-specific survival, new breast primaries, other cancers, ischaemic cardiac and cerebrovascular events and hip (and other) fractures. Participants will be followed-up annually until at least 15 years median follow-up.

It should be noted that the Research Ethics Committee (REC) and Confidentiality Advisory Group (CAG) have already approved the LATTE study for collection of vital HES, cancer registration and mortality data sets as part of this study.

In 2010, results from 10-year follow-up from ATAC demonstrated that there is long-term superiority of anastrozole over tamoxifen as initial adjuvant therapy for post-menopausal women with hormone-sensitive early breast cancer. This paper demonstrated that there were significantly lower rates of local and distant recurrence, as well as reduced contralateral breast cancer in patients treated with anastrozole. However, in 2016 a recent preliminary analysis of the LATTE study demonstrated that the benefits of anastrozole do not continue long-term after 10 years in terms of reduced recurrence rates. The results also suggested that there was a larger reduction of new contralateral tumours with tamoxifen. However, the preliminary analysis was limited in that there was limited data with possible under reporting of vital events inked to the safety and efficacy endpoints; this therefore may diminish the effect of anastrozole. Queen Mary University of London (QMUL) therefore require extended cohort events, obtainable from HES, cancer registration and mortality data in order to conclude the long-term safety of either intervention. QMUL will then be able to integrate the pseudonymised LATTE data with the ATAC data sets in order to perform an analysis of the overall 20-year follow-up period.

Data from a preliminary analysis was presented at the San Antonio Breast Cancer Symposium in December 2016 as a poster. QMUL plan to publish the main results from the LATTE cohort within 12-18 months after receipt of the NHS Digital data. This will enable them to report a more complete data set, with up-to-date information on recurrences, deaths, other primary cancers, and adverse events. To demonstrate a potential carry-over effect of anastrozole versus tamoxifen, long-term follow-up in excess of 10 years is essential. Therefore, after the initial publication in approximately 2020 QMUL plan to publish an updated manuscript on the benefits of AI therapy in 2022/2023. The main target audience for their data outputs are the patients with early breast cancer, and the medical professionals who can use the results for decision making.

Further outputs and analyses of the LATTE study will be published in peer-reviewed medical journals such as The Lancet, The Lancet Oncology, Breast Cancer Research and Treatment and the British Journal of Cancer. Outputs are expected in 2020 when there is 10 years' of follow-up data available.

The public will be made aware of the research progress through the following web page: https://www.qmul.ac.uk/wolfson/research-projects-a-z/current-projects/

The anticipated audiences of the above outputs are researchers, scientists, stakeholders for the wider project and research participants.

Policy makers and public health bodies such as NICE will be targeted with the outputs of the study. NICE will be advised on the long-term safety and efficacy of tamoxifen and anastrozole as adjuvant therapy. These analyses will enable patients and women who have been diagnosed with invasive breast cancer to make a more informed decision on the adjuvant treatment options available to them.

Data contained in any outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

The funder will not have influence on the outcomes nor suppress any of the findings of the research.

Yielded Benefits is not a requirement for new applications.