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      No association between low-dose aspirin use and breast cancer outcomes overall: a Swedish population-based study

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          Abstract

          Background

          Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as well as dose and duration of aspirin use.

          Methods

          We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I–III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model.

          Results

          Among women with stage I–III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77–1.12; use after diagnosis: HR 1.00, 95% CI 0.74–1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I–III breast cancer patients (HR 0.97, 95% CI 0.86–1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29–0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67–1.23).

          Conclusion

          In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.

          Electronic supplementary material

          The online version of this article (10.1186/s13058-018-1065-0) contains supplementary material, which is available to authorized users.

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          Most cited references18

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          Use of statins and the risk of death in patients with prostate cancer.

          To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.
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            Aspirin intake and survival after breast cancer.

            Animal and in vitro studies suggest that aspirin may inhibit breast cancer metastasis. We studied whether aspirin use among women with breast cancer decreased their risk of death from breast cancer. This was a prospective observational study based on responses from 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 and were observed until death or June 2006, whichever came first. The main outcome was breast cancer mortality risk according to number of days per week of aspirin use (0, 1, 2 to 5, or 6 to 7 days) first assessed at least 12 months after diagnosis and updated. There were 341 breast cancer deaths. Aspirin use was associated with a decreased risk of breast cancer death. The adjusted relative risks (RRs) for 1, 2 to 5, and 6 to 7 days of aspirin use per week compared with no use were 1.07 (95% CI, 0.70 to 1.63), 0.29 (95% CI, 0.16 to 0.52), and 0.36 (95% CI, 0.24 to 0.54), respectively (test for linear trend, P < .001). This association did not differ appreciably by stage, menopausal status, body mass index, or estrogen receptor status. Results were similar for distant recurrence. The adjusted RRs were 0.91 (95% CI, 0.62 to 1.33), 0.40 (95% CI, 0.24 to 0.65), and 0.57 (95% CI, 0.39 to 0.82; test for trend, P = .03) for 1, 2 to 5, and 6 to 7 days of aspirin use, respectively. Among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death.
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              Is breast cancer survival improving?

              Despite advances in therapies for breast cancer, improvement in survival for patients with recurrent or metastatic breast cancer has been difficult to establish. The objective of the current study was to determine whether the survival of women with recurrent breast cancer has improved from 1974 to 2000. The authors analyzed the survival experience of 834 women who developed recurrent breast cancer between November 1974 and December 2000. All patients had been treated previously with adjuvant anthracycline-based protocols. Patients were divided into five consecutive groups based on year of breast cancer recurrence, and survival was compared across the five groups. Because some prognostic variables were divided unevenly divided among the cohorts, a multivariate model was created to determine the association of year of recurrence and survival after accounting for other prognostic factors. In the unadjusted analysis, there was a statistically significant improvement in survival across the five groups, and the more recent cohorts had longer survival (P < 0.001). Other variables that predicted longer survival after breast cancer recurrence included smaller initial tumor size, lower stage of disease, fewer lymph nodes involved, longer disease-free interval, estrogen receptor-positive tumors, and nonvisceral dominant site of disease recurrence. In the multivariate analysis, which adjusted for these prognostic factors, year of recurrence was associated with a trend toward improved survival, with a 1% reduction in risk for each increasing year. For these cohorts of patients, the authors present data suggesting that the prognosis for patients with recurrent breast cancer improved between 1974 and 2000. Copyright 2003 American Cancer Society.
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                Author and article information

                Contributors
                +46-8-517 707 06 , gabriella.frisk@ki.se
                sara.ekberg@ki.se
                elisabet.lidbrink@karolinska.se
                sandra.eloranta@ki.se
                malin.sund@surgery.umu.se
                irma.fredriksson@ki.se
                mats.lambe@ki.se
                karin.ekstrom.smedby@ki.se
                Journal
                Breast Cancer Res
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central (London )
                1465-5411
                1465-542X
                20 November 2018
                20 November 2018
                2018
                : 20
                : 142
                Affiliations
                [1 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Medicine Solna, Division of Clinical Epidemiology, , Karolinska Institutet and Karolinska University Hospital, ; SE-171 76 Stockholm, Sweden
                [2 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Oncology–Pathology, , Karolinska Institutet, ; Stockholm, Sweden
                [3 ]ISNI 0000 0001 1034 3451, GRID grid.12650.30, Department of Surgical and Perioperative Sciences, , Umeå University, ; Umeå, Sweden
                [4 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Molecular Medicine and Surgery, , Karolinska Institutet, ; Stockholm, Sweden
                [5 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Breast and Endocrine Surgery, , Karolinska University Hospital, ; Stockholm, Sweden
                [6 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0003-3817-0577
                Article
                1065
                10.1186/s13058-018-1065-0
                6247765
                30458873
                76992626-e65a-4fc1-b11a-1f2a41794935
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 May 2018
                : 19 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004047, Karolinska Institutet;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                aspirin,breast cancer,sweden,registers
                Oncology & Radiotherapy
                aspirin, breast cancer, sweden, registers

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