Publications by authors named "Irma Fredriksson"

37 Publications

Data Resource Profile: Breast Cancer Data Base Sweden (BCBaSe 2.0).

Int J Epidemiol 2021 Sep 2. Epub 2021 Sep 2.

Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.

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http://dx.doi.org/10.1093/ije/dyab139DOI Listing
September 2021

Cancer survival in women diagnosed with pregnancy-associated cancer: An overview using nationwide registry data in Sweden 1970-2018.

Eur J Cancer 2021 Sep 6;155:106-115. Epub 2021 Aug 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, Stockholm, SE-17177, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Background: Pregnancy-associated cancer (PAC) is increasing over time in many countries. We provide a comprehensive, population-based overview of cancer survival in women with PAC across five decades.

Methods: We performed a nationwide cohort study of 121,382 women diagnosed with cancer at age 15-49 between 1970 and 2018 using birth and cancer registers in Sweden. Pregnancy-associated cancer was defined as diagnosed during pregnancy and within one year of delivery, while non-PAC was outside this window. Cox regression estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing cancer mortality for PAC versus non-PAC.

Results: In total, 5079 women had a diagnosis of PAC. Cutaneous malignant melanoma, breast, cervical, thyroid and central nervous system (CNS) were the most common sites of PAC. A higher cancer mortality was observed in PAC versus non-PAC for breast (HR = 1.72, 95% CI 1.54-1.93) and uterine cancer (myometrium/unspecified) (8.62, 2.80-26.53), in which all PAC deaths were uterine sarcomas. Increased mortality was also observed in upper digestive tract cancer diagnosed during pregnancy and colon cancer diagnosed during first year after delivery. Contrary, the HR for CNS tumours was significantly decreased (0.71, 0.55-0.91). Survival after PAC improved for most sites over time, with survival after breast cancer during pregnancy in recent years being similar to that of non-pregnancy associated breast cancer.

Conclusion: For the majority of sites, PAC was not associated with poorer prognosis compared to non-PAC, a finding which was stable over time. The main exceptions were breast cancer and rarer cancers, such as uterine sarcoma.
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http://dx.doi.org/10.1016/j.ejca.2021.07.008DOI Listing
September 2021

Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study.

Breast 2021 Oct 7;59:157-164. Epub 2021 Jul 7.

Department of Oncology, Faculty of Medicine and Health, Örebro University, SE 70182, Örebro, Sweden. Electronic address:

Background: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors.

Methods: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy.

Results: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006-2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32-4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01-2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40-3.25 for arrhythmia; HR 2.03; 95% CI: 1.15-3.58 for ischemic heart disease).

Conclusion: Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.
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http://dx.doi.org/10.1016/j.breast.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281646PMC
October 2021

Risk of primary lung cancer after adjuvant radiotherapy in breast cancer-a large population-based study.

NPJ Breast Cancer 2021 Jun 1;7(1):71. Epub 2021 Jun 1.

Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.

Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of later radiation-induced lung cancer (LC). We examined the risk of primary LC in a population-based cohort of 52300 women treated for BC during 1992 to 2012, and 253796 age-matched women without BC. Cumulative incidence of LC was calculated by the Kaplan-Meier method, and the risk of LC after BC treatment was estimated by Cox proportional hazards regression analyses. Women with BC receiving RT had a higher cumulative incidence of LC compared to women with BC not receiving RT and women without BC. This became apparent 5 years after RT and increased with longer follow-up. Women with BC receiving RT had a Hazard ratio of 1.59 (95% confidence interval 1.37-1.84) for LC compared to women without BC. RT techniques that lower the incidental lung doses, e.g breathing adaption techniques, may lower this risk.
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http://dx.doi.org/10.1038/s41523-021-00280-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169889PMC
June 2021

An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions: Development and Evaluation in Two Separate Cohorts.

Epidemiology 2021 07;32(4):607-615

From the Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions.

Methods: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer.

Results: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6).

Conclusions: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.
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http://dx.doi.org/10.1097/EDE.0000000000001358DOI Listing
July 2021

Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study.

Cancers (Basel) 2021 Mar 9;13(5). Epub 2021 Mar 9.

Department of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.

We compared estrogen receptor (ER), progesterone receptor (PR), human epidermal growth-factor receptor 2 (HER2), Ki67, and grade scores among the pathology departments in Sweden. We investigated how ER and HER2 positivity rates affect the distribution of endocrine and HER2-targeted treatments among oncology departments. All breast cancer patients diagnosed between 2013 and 2018 in Sweden were identified in the National Quality Register for Breast Cancer. Cases with data on ER, PR, HER2, Ki67, grade, and treatment were selected (43,261 cases from 29 departments following the guidelines for biomarker testing). The ER positivity rates ranged from 84.2% to 97.6% with 6/29 labs out of the overall confidence intervals (CIs), while PR rates varied between 64.8% and 86.6% with 7/29 labs out of the CIs. HER2 positivity rates ranged from 9.4% to 16.3%, with 3/29 labs out of the overall CIs. Median Ki67 varied between 15% and 30%, where 19/29 labs showed significant intra-laboratory variability. The proportion of grade-II cases varied between 42.9% and 57.1%, and 13/29 labs were outside of the CI. Adjusting for patient characteristics, the proportion of endocrine and anti-HER2 treatments followed the rate of ER and HER2 positivity, illustrating the clinical effect of inter- and intra-laboratory variability. There was limited variability among departments in ER, PR, and HER2 testing. However, even a few outlier pathology labs affected endocrine and HER2-targeted treatment rates in a clinically relevant proportion, suggesting the need for improvement. High variability was found in grading and Ki67 assessment, illustrating the need for the adoption of new technologies in practice.
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http://dx.doi.org/10.3390/cancers13051166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963154PMC
March 2021

In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study.

Breast Cancer Res 2021 02 1;23(1):17. Epub 2021 Feb 1.

Cancer Registry of Norway, Oslo, Norway.

Background: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death.

Methods: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up.

Results: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes.

Conclusions: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.
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http://dx.doi.org/10.1186/s13058-021-01393-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852363PMC
February 2021

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JNCI Cancer Spectr 2021 Feb 26;5(1):pkaa084. Epub 2020 Sep 26.

Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Although small, node-negative breast cancer (ie, T1abN0) constitutes 20% of all newly diagnosed breast cancers, data on prognosis and prognostic factors are limited.

Methods: We conducted a population-based cohort study including 20 114 Swedish women treated for T1abN0 breast cancer from 1977 onward. Patient and tumor data were collected from Swedish breast cancer registries. Cohort subjects were followed through linkage to the Cause of Death Register. We calculated the cumulative incidence of breast cancer-specific and overall death and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During a median follow-up of 9.1 years (range = 0-38), 915 women died of breast cancer and 5416 of any cause. The 10-, 20-, and 30-year cumulative incidences of breast cancer death were 3.4% (95% CI = 3.1% to 3.7%), 7.6% (95% CI = 7.1% to 8.2%), and 10.5% (95% CI = 9.6% to 11.4%), respectively. The multivariable hazard ratios and 95% confidence intervals of breast cancer death were 0.92 (95% CI = 0.88 to 0.97) for each additional calendar year of diagnosis, 4.38 (95% CI = 2.79 to 6.87) for grade 3 vs grade 1 tumors, 0.43 (95% CI = 0.31 to 0.62) for progesterone receptor-positive vs progesterone receptor-negative disease, and 2.01 (95% CI = 0.99 to 4.07) for HER2-positive vs HER2-negative disease. Women with grade 3 vs grade 1 tumors had a 56% increased risk of death from any cause (HR = 1.56, 95% CI = 1.30 to 1.88).

Conclusions: The risk of breast cancer death in T1abN0 disease continues to increase steadily beyond 10 years after diagnosis, has improved over time, and varies substantially by tumor characteristics.
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http://dx.doi.org/10.1093/jncics/pkaa084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791632PMC
February 2021

Predictive role of HER2-status on the effectiveness of endocrine adjuvant treatment in postmenopausal breast cancer patients: a population-based cohort study.

Breast Cancer Res Treat 2021 Apr 30;186(3):779-789. Epub 2020 Nov 30.

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjoldsvag 20, 751 85, Uppsala, Sweden.

Purpose: There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade.

Methods: A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively.

Results: After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34-0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41-1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14-5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10-3.38, p = 0.345).

Conclusion: Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.
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http://dx.doi.org/10.1007/s10549-020-06022-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019428PMC
April 2021

Treatment patterns, risk for hospitalization and mortality in older patients with triple negative breast cancer.

J Geriatr Oncol 2021 03 12;12(2):212-218. Epub 2020 Sep 12.

Department of Oncology, Faculty of Medicine and Health, Örebro University, SE 70182 Örebro, Sweden; Regional Cancer Center Uppsala-, Orebro, Uppsala, Sweden.

Objectives: To study the treatment patterns, potential risk factors for hospitalization within one year from diagnosis, and causes of death in older patients with triple negative breast cancer (TNBC).

Materials And Methods: We performed a registry-based cohort study using the BCBaSe database which links cases of breast cancer from three Swedish healthcare regions with socioeconomic factors, hospitalizations and causes of death. Women ≥70 years old with non-metastatic TNBC, between 1/12007 and 31/122012 were included (n = 413).

Results: In total, 168 patients (40.7%) received chemotherapy after surgery and 123 patients (30.0%) in the whole cohort had at least one hospitalization within one year from diagnosis. The risk of hospitalization overall was increased in the group receiving chemotherapy (Odds Ratio 2.35, 95% Confidence Intervall: 1.30-4.26) mainly due to toxicities. Cumulative incidence of breast cancer mortality was comparable among different age groups (70-74 vs. 75-79 vs. ≥ 80 years old) whereas non-breast cancer mortality was higher in patients ≥80 years old. Stage at diagnosis and comorbidities were independently associated with both breast cancer-specific- and overall mortality whereas age was only associated with overall mortality.

Conclusions: The use of chemotherapy in older patients with TNBC was associated with age, tumor stage, and comorbidities. Chemotherapy use was also associated with increased risk for hospitalization within one year from diagnosis. Although the impact of chemotherapy on mortality was analyzed in a multivariate manner showing neither increased or decreased mortality, no firm conclusion can be drawn due to unmeasured confounders.
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http://dx.doi.org/10.1016/j.jgo.2020.09.004DOI Listing
March 2021

Impact of chemotherapy, radiotherapy, and endocrine therapy on sick leave in women with early-stage breast cancer during a 5-year period: a population-based cohort study.

Breast Cancer Res Treat 2020 Aug 6;182(3):699-707. Epub 2020 Jun 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77, Stockholm, Sweden.

Purpose: To examine the influence of type of oncological treatment on sick leave in women of working age with early-stage breast cancer.

Methods: We identified 8870 women aged 30-64 diagnosed with stage I-II breast cancer between 2005 and 2012 in the Breast Cancer Data Base Sweden. Associations between type of oncological treatment (radiotherapy, endocrine therapy, and chemotherapy) and sick leave were estimated by hazard ratios, probabilities, and length of sick leave using multi-state survival analysis.

Results: During the first 5 years after diagnosis, women aged 50-54 years at diagnosis receiving chemotherapy spent on average 182 (95% CI 151-218) additional days on sick leave compared with women not receiving chemotherapy, but with otherwise similar characteristics. Correspondingly, women initiating endocrine therapy spent 30 (95% CI 18-44) additional days on sick leave and women receiving post-mastectomy radiotherapy 53 (95% CI 37-69) additional days. At year five, the rate of sick leave was increased in women who had received chemotherapy (HR 1.19, 95% CI 1.11-1.28) or endocrine therapy (HR 1.15, 95% CI 1.05-1.26). Chemotherapy and endocrine therapy were associated with increased rates of sick leave due to depression or anxiety.

Conclusion: Our findings of increased long-term risks of sick leave after oncological treatment for breast cancer warrant attention from caregivers taking part in cancer rehabilitation. In light of the ongoing debate about overtreatment of early-stage breast cancer, our findings point to the importance of properly selecting patients for chemotherapy not only for the medical toxicity but also the possible impact on their livelihood.
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http://dx.doi.org/10.1007/s10549-020-05720-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320921PMC
August 2020

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

Cancer 2020 07 11;126(13):2971-2979. Epub 2020 May 11.

Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.

Methods: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.

Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]).

Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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http://dx.doi.org/10.1002/cncr.32859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318598PMC
July 2020

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

J Med Screen 2021 03 5;28(1):34-38. Epub 2020 May 5.

Regional Cancer Center Stockholm Gotland, Stockholm, Sweden.

Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome.

Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.

Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range.

Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.
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http://dx.doi.org/10.1177/0969141320921210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905745PMC
March 2021

Bleeding risk in breast cancer patients during concomitant administration of warfarin and tamoxifen: A population-based nested case-control study.

Breast J 2020 05 28;26(5):981-987. Epub 2020 Jan 28.

Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.

We aimed to investigate whether the concomitant use of tamoxifen with warfarin is associated with higher risk for bleeding among patients with early estrogen-receptor (ER)-positive breast in a population-based nested case-control study. We identified 1787 patients taking warfarin and 92 cases hospitalized for bleeding and found an adjusted odds ratio (OR) of 1.42 (95% confidence interval (CI): 0.84-2.40) for the risk of bleeding in patients treated with warfarin that initiated tamoxifen within the previous 30 days. As a result, we could not definitively rule out a potential association between tamoxifen use during warfarin and bleeding risk in patients with breast cancer.
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http://dx.doi.org/10.1111/tbj.13759DOI Listing
May 2020

Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort.

Breast Cancer Res 2020 01 22;22(1):10. Epub 2020 Jan 22.

Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.

Background: Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC.

Methods: The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 (n = 60,217) and age-matched women without a history of BC (n = 300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method.

Results: Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88-0.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01-1.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06-1.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up.

Conclusions: Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.
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http://dx.doi.org/10.1186/s13058-020-1249-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977272PMC
January 2020

Causes of sick leave, disability pension, and death following a breast cancer diagnosis in women of working age.

Breast 2019 Jun 2;45:48-55. Epub 2019 Mar 2.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Regional Cancer Center, Uppsala University Hospital, Uppsala, Sweden.

Objectives: Women diagnosed with breast cancer during working age are at increased risk of permanent absence from work, but the underlying medical causes have rarely been studied. We examined the risk of cause-specific sick leave, disability pension, and the competing event death after a breast cancer diagnosis in a population-based cohort study.

Materials And Methods: From the Breast Cancer Data Base Sweden, we identified 16,603 women diagnosed with stage I-III breast cancer between 2000 and 2012, and 63,773 control women. Using multi-state modelling, we calculated probabilities and durations of sick leave, disability pension, and death by registered cause, together with cause-specific hazard ratios.

Results: Five years after diagnosis, causes other than cancer accounted for around half of all sick leave (3.5% out of 6.8% of women) and disability pension (1.4% out of 2.6%) in women with breast cancer. Compared with control women, women with breast cancer were at increased risk of sick leave and disability pension due to mental disorders (HR 1.24, 95% CI 1.15-1.33 and HR 1.54, 95% CI 1.29-1.85, respectively) and disability pension due to inflammatory diseases (HR 1.46, 95% CI 1.05-2.03). The risk of sick leave and disability pension due to cardiovascular disease was also elevated, although only statistically significant for disability pension in women diagnosed after 2005 (HR 2.24, 95% CI 1.22-4.13).

Conclusion: Follow-up, support, and rehabilitation programs for women diagnosed with breast cancer must address a wide range of psychological and physical conditions to limit the consequences on working life.
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http://dx.doi.org/10.1016/j.breast.2019.02.012DOI Listing
June 2019

Diagnostic pathways and management in women with pregnancy-associated breast cancer (PABC): no evidence of treatment delays following a first healthcare contact.

Breast Cancer Res Treat 2019 Apr 14;174(2):489-503. Epub 2018 Dec 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Women with pregnancy-associated breast cancer (PABC), i.e. diagnosed during or within 2 years of pregnancy, have a poor prognosis. We compared symptoms, diagnostics, treatments, and waiting times from first symptoms to treatment initiation in women diagnosed with PABC and non-PABC.

Materials And Methods: Women diagnosed with PABC and non-PABC at ages 15-44 were identified in Swedish healthcare registers. Chart information was retrieved for 546 women (273 PABC cases and 273 age- and hospital-matched non-PABC controls) treated at 11 hospitals across Sweden between 1992 and 2009. Distributions of symptoms, diagnostics and treatments were compared. Median waiting times from initial symptoms to start of treatment, and time periods within, were estimated from Kaplan-Meier curves.

Results: Initial symptoms in women with PABC and non-PABC were similar. Women with PABC more often underwent biopsy and ultrasound than mammography at initial examination. Compared to non-PABC, rates of mastectomy and axillary clearance were higher in women with PABC, while endocrine treatment was less common. The time from symptoms to first healthcare contact was non-significantly longer in women diagnosed during or within 6 months of pregnancy. Waiting times from contact with healthcare to diagnosis and treatment were shorter or similar in women with PABC compared to women with non-PABC.

Conclusions: These findings do not support the notion that diagnostic and treatment delays following a first healthcare contact are more common in women diagnosed with breast cancer during or shortly after pregnancy. However, there was some evidence of delays in seeking healthcare among pregnant and lactating women.
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http://dx.doi.org/10.1007/s10549-018-05083-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422971PMC
April 2019

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

Breast Cancer Res 2018 11 20;20(1):142. Epub 2018 Nov 20.

Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1186/s13058-018-1065-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247765PMC
November 2018

Prognosis in patients diagnosed with loco-regional failure of breast cancer: 34 years longitudinal data from the Stockholm-Gotland cancer registry.

Breast Cancer Res Treat 2018 Dec 17;172(3):703-712. Epub 2018 Sep 17.

Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Rationale: Survival after loco-regional failure (LRF) of breast cancer was investigated at the population level.

Methods: Using the Stockholm cancer registry, 2698 patients diagnosed with LRF between 1980 and 2014 were identified and divided into three cohorts by year of LRF diagnosis. Post-relapse event-free survival (EFS) and overall survival (OS) were analyzed separately in local and loco-regional relapses and compared across the cohorts by Kaplan-Meier method. Relative survival was estimated and Poisson regression models, adjusted for clinically relevant prognostic factors, were fitted for excess mortality ratio calculation. Age-related survival trends were also explored.

Results: Among 1922 patients diagnosed with local relapse, 1032 (54%) EFS events and 931 (48%) deaths were registered. A significant improvement in EFS (p < 0.001) and OS (p < 0.001) was demonstrated in tumors that recurred locally in the years 1990-1999 and 2000-2014 compared with 1980-1989, regardless of age at relapse (≤ 60 years; > 60 years). In women with loco-regional relapse, 557 out of 776 (72%) experienced a post-relapse event and 522 (67%) died. Significantly longer EFS and OS were seen over time in the whole group (p < 0.001 and p = 0.003, respectively) and in younger (p < 0.001; p < 0.001) but not in older women (p = 0.55; p = 0.80). Relative survival was consistent with OS and a statistically significant decrease in mortality after loco-regional recurrence over time was seen only in women aged ≤ 60 years.

Conclusions: Survival after loco-regional failure of breast cancer has improved over time, especially in younger women.
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http://dx.doi.org/10.1007/s10549-018-4936-2DOI Listing
December 2018

Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors.

Breast Cancer Res 2018 07 4;20(1):64. Epub 2018 Jul 4.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Background: Adjuvant radiotherapy is the standard of care after breast-conserving surgery for primary breast cancer, despite a majority of patients being over- or under-treated. In contrast to adjuvant endocrine therapy and chemotherapy, no diagnostic tests are in clinical use that can stratify patients for adjuvant radiotherapy. This study presents the development and validation of a targeted gene expression assay to predict the risk of ipsilateral breast tumor recurrence and response to adjuvant radiotherapy after breast-conserving surgery in primary breast cancer.

Methods: Fresh-frozen primary tumors from 336 patients radically (clear margins) operated on with breast-conserving surgery with or without radiotherapy were collected. Patients were split into a discovery cohort (N = 172) and a validation cohort (N = 164). Genes predicting ipsilateral breast tumor recurrence in an Illumina HT12 v4 whole transcriptome analysis were combined with genes identified in the literature (248 genes in total) to develop a targeted radiosensitivity assay on the Nanostring nCounter platform. Single-sample predictors for ipsilateral breast tumor recurrence based on a k-top scoring pairs algorithm were trained, stratified for estrogen receptor (ER) status and radiotherapy. Two previously published profiles, the radiosensitivity signature of Speers et al., and the 10-gene signature of Eschrich et al., were also included in the targeted panel.

Results: Derived single-sample predictors were prognostic for ipsilateral breast tumor recurrence in radiotherapy-treated ER+ patients (AUC 0.67, p = 0.01), ER+ patients without radiotherapy (AUC = 0.89, p = 0.02), and radiotherapy-treated ER- patients (AUC = 0.78, p < 0.001). Among ER+ patients, radiotherapy had an excellent effect on tumors classified as radiosensitive (p < 0.001), while radiotherapy had no effect on tumors classified as radioresistant (p = 0.36) and there was a high risk of ipsilateral breast tumor recurrence (55% at 10 years). Our single-sample predictors developed in ER+ tumors and the radiosensitivity signature correlated with proliferation, while single-sample predictors developed in ER- tumors correlated with immune response. The 10-gene signature negatively correlated with both proliferation and immune response.

Conclusions: Our targeted single-sample predictors were prognostic for ipsilateral breast tumor recurrence and have the potential to stratify patients for adjuvant radiotherapy. The correlation of models with biology may explain the different performance in subgroups of breast cancer.
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http://dx.doi.org/10.1186/s13058-018-0978-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033283PMC
July 2018

Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ.

Breast Cancer Res Treat 2018 Aug 5;171(1):95-101. Epub 2018 May 5.

Department of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden.

Purpose: The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS.

Methods: The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed.

Results: Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT).

Conclusions: The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.
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http://dx.doi.org/10.1007/s10549-018-4803-1DOI Listing
August 2018

Loss in working years after a breast cancer diagnosis.

Br J Cancer 2018 03 23;118(5):738-743. Epub 2018 Jan 23.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, Stockholm SE-171 77, Sweden.

Background: Breast cancer can negatively influence working life, but it is unclear how many working years women with breast cancer can expect to lose.

Methods: Women diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N=19 661), together with breast cancer-free comparison women (N=81 303). Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and without breast cancer.

Results: Women aged 50 years at diagnosis with stage I disease lost on average 0.5 years (95% CI, 0.2-0.7) of their remaining working time; the corresponding estimates were 0.9 years (0.5-1.2) in stage II, 2.5 years (1.9-3.1) in stage III and 8.1 years (6.5-9.7) in stage IV. Women with in situ breast cancer did not lose any working years. The strongest treatment determinant was axillary lymph node dissection.

Conclusions: We found a loss in working years not only in late but also in early-stage breast cancer. Although it is reassuring that some groups had no or only a modest work loss, the economic consequences for society are considerable given the large number of women annually diagnosed with breast cancer.
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http://dx.doi.org/10.1038/bjc.2017.456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846067PMC
March 2018

Tumor characteristics and prognosis in women with pregnancy-associated breast cancer.

Int J Cancer 2018 04 4;142(7):1343-1354. Epub 2017 Dec 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15-44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (tumor size, nodal status, metastasis), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years postdelivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year postdelivery) and 3,598 during 2-10 years postdelivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and nonsignificant. The poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.
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http://dx.doi.org/10.1002/ijc.31174DOI Listing
April 2018

Breast cancer in young women and prognosis: How important are proliferation markers?

Eur J Cancer 2017 10 29;84:278-289. Epub 2017 Aug 29.

Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Department of Breast- and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.

Aim: Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.

Methods: Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.

Results: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]).

Conclusions: The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
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http://dx.doi.org/10.1016/j.ejca.2017.07.044DOI Listing
October 2017

Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells.

J Natl Cancer Inst 2017 03;109(3):1-14

Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer.

Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ERβ-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis.

Results: We identified an absence of ERα but upregulation of ERβ in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ERβ caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate < 0.001) upregulated in ERβ-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ERβ (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts.

Conclusion: We identify ERβ as a mediator of estrogen action in BSCs and a novel target for endocrine therapy.
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http://dx.doi.org/10.1093/jnci/djw236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441302PMC
March 2017

[Worse prognosis for young women with breast cancer].

Lakartidningen 2017 02 14;114. Epub 2017 Feb 14.

Karolinska Universitetssjukhuset Brost- och Endokrinkirurgiska Kliniken - Stockholm, Sweden Karolinska Universitetssjukhuset Brost- och Endokrinkirurgiska Kliniken - Stockholm, Sweden.

Breast cancer in young women is uncommon, but the second most frequent cause of death in this age group. Young women with breast cancer have a worse prognosis than middle-aged women, with a higher risk of local recurrence, distant disease and breast cancer death. This can partly be explained by diagnosis at a later stage, and a higher proportion of tumors with unfavourable characteristics. However, in women with tumors of the luminal B subtype, low age remained an independent prognostic factor of DDFS and LRFS after correction for stage, tumor characteristics and treatment. Treatment of young women with breast cancer requires special skills to deal with the age group-specific questions concerning heredity, sexuality, fertility, and pregnancy.
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February 2017

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

Sci Rep 2016 11 30;6:38037. Epub 2016 Nov 30.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers.
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http://dx.doi.org/10.1038/srep38037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128815PMC
November 2016

Long-term outcome in young women with breast cancer: a population-based study.

Breast Cancer Res Treat 2016 11 13;160(1):131-143. Epub 2016 Sep 13.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Purpose: Whether young age at diagnosis of breast cancer is an independent risk factor for death remains controversial, and the question whether young age should be considered in treatment decisions is still to be answered.

Methods: From a population-based cohort of 22,017 women with breast cancer, all women <35 years (n = 471) were compared to a random sample of 700 women aged 35-69 years from the same cohort. Information on patient and tumor characteristics, treatment, and follow-up was collected from the medical records. Tissue microarrays were produced for analysis of classical biomarkers. Breast cancer-specific survival (BCSS), distant disease-free survival (DDFS), and locoregional recurrence-free survival (LRFS) by age were compared using women 50-69 years as reference.

Results: At 10 years follow-up, women <35 years and 35-39 years had a worse BCSS [age <35 years 69 % (HR 2.75, 95 % CI 1.93-3.94), age 35-39 years 76 % (HR 2.33, 95 % CI 1.54-3.52), age 40-49 years 84 % (HR 1.53, 95 % CI 0.97-2.39), and age 50-69 years 89 % (reference)]. The worse BCSS was statistically significant in stages I-IIa and Luminal B tumors. At multivariate analysis age <35 years and 35-39 years confined a risk in LRFS (HR 2.13, 95 % CI 1.21-3.76 and HR 1.97, 95 % CI 1.06-3.68) but not in DDFS and BCSS. In the subgroup of women <40 years with luminal tumors stage I-IIa, low age remained an independent risk factor also in DDFS (HR 1.87, 95 % CI 1.03-3.44).

Conclusion: Young women have a high risk of systemic disease even when diagnosed in an early stage. The excess risk of relapse is most pronounced in Luminal B tumors, where low age is an independent prognostic factor of DDFS and LRFS.
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http://dx.doi.org/10.1007/s10549-016-3983-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050247PMC
November 2016

Effect of selective serotonin reuptake inhibitors use on endocrine therapy adherence and breast cancer mortality: a population-based study.

Breast Cancer Res Treat 2016 Sep 5;159(2):293-303. Epub 2016 Aug 5.

Division of Cancer Studies, Cancer Epidemiology Unit, School of Medicine, King's College London, London, UK.

The purpose of the study was to investigate whether the concomitant use of selective serotonin reuptake inhibitors (SSRI) with tamoxifen influences the risk of death due to breast cancer, and we also investigated the association between SSRI use and adherence to oral endocrine therapy (ET). We analyzed data from BCBaSe Sweden, which is a database created by the data linkage of Registries from three different regions of Sweden. To investigate the association between ET adherence and SSRI use, we included all women who were diagnosed with non-distant metastatic ER-positive invasive breast cancer from July 2007 to July 2011 and had at least one dispensed prescription of oral tamoxifen or aromatase inhibitor. To investigate the role of concurrent administration of SSRI and tamoxifen on breast cancer prognosis, we performed a nested case-control study. In the adherence cohort, 9104 women were included in the analyses. Women who received SSRI, either before or after breast cancer diagnosis, were at higher risk for low adherence to ET. However, when the overlapping period between SSRI use and ET was >50 %, no excess risk for low adherence was observed. Non-adherence (<80 %) to ET was significantly associated with worse breast cancer survival (OR 4.07; 95 % CI 3.27-5.06). In the case-control study, 445 cases and 11125 controls were included. The concomitant administration of SSRI and tamoxifen did not influence breast cancer survival, neither in short-term (OR 1.41; 95 % CI 0.74-2.68) nor in long-term SSRI users (OR 0.85; 95 % CI 0.35-2.08). Concomitant SSRI and tamoxifen use does not seem to increase risk for death due to breast cancer. Given the positive association between continuing antidepressive pharmacotherapy for a longer period of time and adherence to ET, it is essential to capture and treat depression in breast cancer patients to secure adherence to ET.
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http://dx.doi.org/10.1007/s10549-016-3928-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012147PMC
September 2016

Time trends in axilla management among early breast cancer patients: Persisting major variation in clinical practice across European centers.

Acta Oncol 2016 Jun 15;55(6):712-9. Epub 2016 Feb 15.

a Division of Clinical Epidemiology and Aging Research , German Cancer Research Center (DKFZ) , Heidelberg , Germany ;

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79-96% and 49-92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.
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http://dx.doi.org/10.3109/0284186X.2015.1136751DOI Listing
June 2016
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