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Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Umeå University Hospital, Sweden .
Karolinska University Hospital, Sweden .
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND

Tamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.

METHODS

Our study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).

RESULTS

In the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.

CONCLUSIONS

In this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.

Place, publisher, year, edition, pages
2014.
Keyword [en]
breast cancer, tamoxifen, adjuvant treatment, second primary cancer, lung cancer
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-112285OAI: oai:DiVA.org:liu-112285DiVA: diva2:765171
Available from: 2014-11-21 Created: 2014-11-21 Last updated: 2015-03-31Bibliographically approved
In thesis
1. Long-term effects of adjuvant tamoxifen treatment on cardiovascular disease and cancer
Open this publication in new window or tab >>Long-term effects of adjuvant tamoxifen treatment on cardiovascular disease and cancer
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aims of this thesis were to investigate the long-term effects of adjuvant tamoxifen treatment on breast cancer recurrence and mortality, cardiovascular disease, and the incidence of secondary cancer.

Between 1982 and 1992, postmenopausal patients with early stage breast cancer were included in a randomized clinical study of 2 or 5 years of postoperative tamoxifen therapy. The trial was planned by the Swedish Breast Cancer Group, and it included 4610 patients. Follow-up on causes of death, hospitalizations and secondary cancers were obtained from national population-based registries. 

All-cause mortality, breast cancer-specific mortality and mortality from coronary heart disease were decreased in the 5-year group, but the incidence of endometrial cancer was increased (Paper I). The incidence and mortality of cerebrovascular diseases were increased during the active treatment phase, and reduced after the active treatment (Paper II). Similar results were seen for subgroups of cerebrovascular diseases such as stroke and ischemic stroke. In the 5-year group, the morbidity from coronary heart disease was reduced during treatment but not after treatment was stopped (Paper III). This was the case also for heart failure and for atrial fibrillation/flutter. For secondary cancers the lung cancer risk was reduced, as well as the lung cancer mortality (Paper IV). An increased risk was observed for endometrial cancer, but appeared to decrease over time. The risk of contralateral breast cancer was reduced, with most of the reduction after treatment was stopped. For distance recurrences the risk was reduced both during treatment and a few years after treatment was stopped. The breast cancer mortality was also reduced, especially during the post-treatment phase.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 45 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1430
Keyword
Adjuvant, adverse events, breast cancer, cerebrovascular disease, coronary heart disease, heart failure, lung cancer, second primary cancer, tamoxifen
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112085 (URN)10.3384/diss.diva-112085 (DOI)978-91-7519-182-9 (ISBN)
Public defence
2014-12-19, Eken, ingång 65, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-11-21 Created: 2014-11-13 Last updated: 2014-11-21Bibliographically approved

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Rosell, JohanNordenskjöld, BoStål, OlleCarstensen, John

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Division of Clinical SciencesFaculty of Health SciencesRegional Cancer Center South East SwedenDepartment of OncologyDivision of Health Care Analysis
Public Health, Global Health, Social Medicine and EpidemiologyCancer and Oncology

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