Prognostic tools for determining patients with indolent breast cancers (BCs) are far from optimal, leading to extensive overtreatment. Several studies have demonstrated mRNAs, lncRNAs and miRNAs to have prognostic potential in BC. Because mRNAs, lncRNAs, and miRNAs capture distinct transcriptomic information, we hypothesized that combining them would improve classification performance. Our pair-matched design study included fresh frozen primary tumor samples from 160 lymph node negative and systemically untreated BC patients of which 80 developed recurrence while 80 remained recurrence-free (mean follow-up of 20.9 years). We integrated three classes of RNA and subsequently performed classification using seven machine learning methods followed by a voting scheme. Under the criteria of ≥ 90

The anti-cancer potential of low-dose aspirin in long-term breast cancer (BC) survivors remain unknown. We evaluated the association between low-dose aspirin use and BC recurrence and mortality. Women ≥40 years diagnosed with stage I-III BC (1996–2004) were identified from the Danish Breast Cancer Group (DBCG) database and information on aspirin use from the Danish Prescription Registry. We ascertained recurrences from DBCG and via a validated algorithm. We plotted cumulative incidences of recurrence and mortality, accounting for competing risks. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CI), employing landmark analyses at 5-, 10-, and 15-year post-diagnosis. Among 20,509 BC survivors, 4527 developed recurrence over 232,441 person-years of follow-up. The 20-year cumulative incidence of recurrence was lower in users (17.8%) than nonusers (22.4%), with similar trends among 10-year disease-free survivors (9.9% vs. 12.7%). We observed reduced HRs of recurrence (adjusted HR5-year = 0.80, (95% CI = 0.66-0.98); HR10-year = 0.87 (0.73–1.05); HR15-year = 0.82 (0.57–1.17) in aspirin users, but increased HRs of all-cause mortality (HR5-year = 1.08 (0.96–1.21); HR10-year = 1.09 (0.96–1.24); HR15-year = 1.09 (0.80–1.31). The reduced recurrence risk in aspirin users may indicate potential anti-cancer effects of aspirin, though the increased risk of death suggests influence by confounding by indication and competing risks.

Background and purpose: Despite advancements in genetic testing and expanded eligibility criteria, underutilisation of germline testing for pathogenic variants in BRCA1 and BRCA2 (BRCA) remains evident among breast cancer (BC) patients. This observational cohort study presents real-world data on BRCA testing within the context of clinical practice challenges, including incomplete family history and under-referral. Material and methods: From the Danish Breast Cancer Group (DBCG) clinical database, we included 65,117 females with unilateral stage I–III BC diagnosed in 2000–2017, of whom 9,125 (14%) were BRCA tested. Test results spanned from 1999 to 2021. We evaluated test rates overall and in three diagnosis periods. In logistic regression models, we examined the correlation between a BRCA test and patients’ age, residency region, receptor status, and diagnosis period. Results: Test rates rose most significantly among patients aged under 40 years, increasing from 47% (2000–2005) to 88% (2012–2017), albeit with regional discrepancies. Test timing shifted in recent years, with most results within 6 months of BC diagnosis, primarily among the youngest patients. BRCA test rates were higher for oestrogen receptor-negative/human epidermal growth factor receptor 2-negative BC (25% in 2000–2005 vs. 38% in 2012–2017), and these findings were confirmed in multivariate regression models. Interpretation: Our results indicate a critical need for an intensified focus on BRCA testing among BC patients older than 40, where a mainstreamed testing approach might overcome delayed or missed testing. Current DBCG guidelines recommend BRCA testing of all BC patients younger than 50 years, while a general recommendation for older patients is still missing.

Background: Breast cancer is the most commonly diagnosed malignancy among women worldwide. Despite high survival rates, 20%-40% of women will experience a recurrence, with risks extending beyond 20 years after diagnosis. Premenopausal women diagnosed with estrogen receptor (ER) positive disease are prescribed 5-10 years of tamoxifen therapy to prevent a recurrence. 17β-hydroxysteroid dehydrogenase 1 and 2 expression (HSD17B1 and HSD17B2, respectively) regulate the relative concentrations of estrogen metabolites and may modify tamoxifen effectiveness. We evaluated the prognostic and predictive value of these biomarkers. Methods: Premenopausal women diagnosed during 2002-2011 with a first primary stage I-III breast cancer were identified in the Danish Breast Cancer Group database, and categorized based on ER status and receipt of tamoxifen (4600 ER+/TAM+ and 1359 ER−/TAM−). HSD17B1 and HSD17B2 were assayed by immunohistochemistry and scored using automated image analysis [Visiopharm (Hoersholm, Denmark)]. The biomarkers were assessed within ER/TAM strata, to differentiate the enzymes predictive of treatment response from enzymes prognostic for breast cancer recurrence. We used Cox proportional hazards regression and probabilistic bias analysis to account for mismeasurement of biomarker expression and baseline selection bias from tumor sample availability to calculate the hazard ratios (HRs) and 95% simulation intervals (SIs) associating each biomarker with recurrence. Results: 24% of ER+/TAM+ and 13% of ER−/TAM− breast cancers had any HSD17B1 expression. In the bias-adjusted analyses, women diagnosed with tumors positive for HSD17B1 expression had an increased rate of recurrence: HR=1.40 (95% SI: 1.02, 2.92) in the ER+/TAM+ stratum, and HR=1.32 (95% SI: 0.82, 2.74) in the ER−/TAM− stratum. A 10-unit increase in HSD17B2 expression corresponded with a decreased recurrence rate among women in the ER+/TAM+ (HR=0.85, 95% SI: 0.69, 1.05) stratum, but not among women in the ER−/TAM− stratum (HR=1.07, 95% SI: 0.82, 1.42). Conclusions: We observed that HSD17B1 expression was associated with a higher rate of recurrence among premenopausal women, and that HSD17B2 expression was associated with a lower rate of recurrence among premenopausal tamoxifen-treated women diagnosed with ER+ disease. HSD17B1 may be an important prognostic marker of breast cancer recurrence among premenopausal breast cancer patients and HSD17B2 may be predictive of response among tamoxifen-treated premenopausal women diagnosed with ER+ breast cancer. Citation Format: Lindsay Jane Collin, Anders Kjaersgaard, Thomas P. Ahern, Michael Goodman, Lauren E. McCullough, Lance A. Waller, Kristina B. Christensen, Per Damkier, Stephen J. Hamilton-Dutoit, Kristina Lauridsen, Peer M. Chistiansen, Bent Ejlertsen, Henrik Toft Sorensen, Deirdre Cronin-Fenton, Timothy L. Lash. 17β-hydroxysteroid dehydrogenases 1 and 2: potential markers for breast cancer recurrence and tamoxifen resistance among premenopausal women diagnosed with breast cancer in Denmark [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 757.

Among women with primary metastatic breast cancer (pMBC), around 5 % of women with primary invasive breast cancer, high-risk mutations associated with disease progression and poor prognosis is shown. The heterogeneity and clinical implications of these genomic alterations remains to be fully elucidated. We performed comprehensive gene mapping on 211 tumors of women diagnosed with pMBC at Rigshospitalet 2014-2021. After DNA purification 203 tumor samples were eligible for analysis. Median age in our cohort was 69 years, 68 % were ER-positive/HER2-negative, 23 % HER2-positive and 9 % triple-negative. A high tumor mutational burden (TMB), shown in 10 %, was in univariable analysis associated with a poor prognosis and a median overall survival of 5.3 months (95 % CI, 2.5-51.3) but no significant association after adjusting for subtype and age. 65 % of tumors had an actionable biomarker, including a PIK3CA mutation in 39 %. TP53 mutations were found in 33 % of tumors and were associated with an increased risk of death (adjusted HR: 1.60, 95 % CI; 1.07-2.40). We have found that for women with pMBC, the disease is driven by several targetable genetic mutations across subtypes, however our results suggest a reduced prognostic value of TMB for this complex patient group. Taken together, our findings substantiate the value of early genomic profiling to actively identify women that may be eligible for a more individualized treatment scheme.

PURPOSE:Premenopausal, estrogen receptor (ER)-positive breast cancer patients should receive tamoxifen for at least 5 years, but many prematurely discontinue. Activation, transport, and deactivation of tamoxifen and its metabolites are controlled by proteins encoded by genes with functional variations. We examined the impact of genetic polymorphisms in the tamoxifen pathway on early treatment discontinuation. METHODS:We included premenopausal women diagnosed with ER-positive breast cancer (2002-2011) in Denmark who initiated tamoxifen. We genotyped 26 genetic variants in 15 enzymes involved in tamoxifen metabolism. Early discontinuation was defined as tamoxifen use for < 5 years. We estimated individual and combined effects of genetic variants using a Bayesian pathway approach. We report Bayes Factors (BF), wherein values > 1 indicate support of an effect of the genetic pathway on discontinuation (compared with no effect). RESULTS:Among 3,729 patients, 536 (14%) discontinued tamoxifen within 5 years. Genetic variants involved in tamoxifen activation impacted early discontinuation (BF = 7.5), in a manner driven almost entirely by CYP2D6 activity (BF = 22.6). Several variants in CYP2D6 and transporter genes synergistically increased the hazard of early discontinuation (e.g., CYP2D6*2 and ABCC2; BF = 138). CONCLUSIONS:Variants in enzymes responsible for activating tamoxifen metabolites-particularly within CYP2D6-influence early tamoxifen discontinuation. CYP2D6 variants synergistically interact with transporter gene variants, namely ABCC2, to further raise the risk of discontinuation.

NCIC-CTG MA.5 and DBCG 89D are symmetrically designed randomized trials comparing adjuvant cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in high-risk breast cancer patients. In a joint analysis we evaluate the predictive value in terms of anthracycline benefit of molecular subtyping by PAM50. A statistically significant interaction (P = 0.008) between continuous Risk of Recurrence (ROR) score and treatment regimen is evident, translating into a clear distinct treatment effect according to ROR score category with HR 0.51 for ROR score ≥ 72 and HR 1.10 for ROR score < 52 (Pinteraction = 0.004). The analysis provides evidence of the benefit from anthracycline in HER2-enriched subtype; for patients with discordance of HER2 subtype and clinical HER2 status, HER2-enriched subtype was predictive of anthracycline benefit whereas clinical HER2 positive status was not. Anthracycline-based adjuvant chemotherapy may safely be withheld for patients with a low ROR score while the benefit increases with increasing ROR score.

BACKGROUNDDecoding the clinical impact of genetic variants is particularly important for precision medicine in cancer. Genetic screening of mainly patients with breast and ovarian cancer has identified numerous BRCA1/BRCA2 variants of uncertain significance (VUS) that remain unclassified owing to a lack of pedigrees and functional data.METHODSHere, we used CRISPR-Select - a technology that exploits unique inbuilt controls at the endogenous locus - to assess 54 rare ClinVar VUS located in the PALB2-binding domain of BRCA2. Variant deleteriousness was examined in the absence and presence of PARPi, cisplatin, or mitomycin C.RESULTSMarked functional deficiency was observed for variants in the exon 2 donor splice region (A22 = c.66A>C, A22 = c.66A>G, A22 = c.66A>T, and D23H) and Trp31 aa (W31G, W31L, and W31C), both critical for BRCA2 function. Moreover, T10K and G25R resulted in an intermediate phenotype, suggesting these variants are hypomorphic in nature. Combining our functional results with the latest ClinGen BRCA1/2 Variant Curation Expert Panel recommendations, we classified 49 of the 54 VUS as either likely benign (n = 45) or likely pathogenic (n = 4).CONCLUSIONTherefore, CRISPR-Select is an important tool for efficient variant clinical classification. Application of this technology in the future will ultimately improve patient care.FUNDINGDanish Cancer Society, Novo Nordisk Foundation, Sygeforsikring Danmark, Børnecancerfonden, Neye-Fonden, Roche, Novartis, Pfizer, AstraZeneca, MSD, and Daiichi Sankyo Europe GmbH.

Purpose:Statin use has been consistently associated with improved clinical outcomes (especially recurrence) in breast cancer in multiple observational studies backed by compelling preclinical evidence. The strength of this evidence warrants a clinical trial to test the efficacy of statin exposure on breast cancer recurrence. Patients and Methods:The double-blind, phase III, randomized, placebo-controlled MASTER (MAmmary cancer STatins in ER positive breast cancer) trial includes women diagnosed with early-stage, estrogen receptor-positive (ER+) breast cancer who are candidates for systemic (neo)adjuvant therapy. Enrolled patients are given standard (neo)adjuvant therapy and additionally randomized to either atorvastatin (80 mg/day) or placebo for two years. The trial's primary outcome is invasive disease-free survival (IDFS), with a target accrual of 3360 patients in total to achieve 80% power (two-sided alpha=0.05) to detect a 25% reduction in the risk of an IDFS event comparing the statin and placebo arms. At 3-, 6-, 12-, and 24-month follow-up time points, patients will have blood drawn for biomarker studies, answer patient-reported outcome (PRO) questionnaires, and control for adverse events. Subsequently, patients will receive annual PRO-criteria for Adverse Events (CTCAE) questionnaires until the completion of their 10 years of follow-up. Secondary endpoints include additional clinical endpoints; pathological response (neo-adjuvant treated patients), recurrence-free survival, distant-recurrence-free interval, overall survival and cardiac death-free interval, co-morbidity, and health-related quality-of-life measured by PRO-CTCAE questionnaires during and beyond study medication. Translational endpoints are evaluated in collected blood- and tumor samples. Discussion:If a protective effect of statins on breast cancer recurrence is supported by evidence from the MASTER trial, then the indications for a safe, well-tolerated, and inexpensive treatment can be expanded towards improved clinical outcomes for breast cancer patients.

Accurate identification of HER2-low breast cancers remains challenging using standard IHC. We analyzed 3182 breast tumors using transcriptomics, revealing detectable ERBB2 mRNA in 86% of IHC 0 cases. Pathological complete response was most prevalent in anti-HER2-treated patients with highest ERBB2 expression. Our results demonstrate that transcriptomics can sensitively detect HER2 expression and stratify patients beyond IHC classification, supporting its use as a complementary biomarker for guiding anti-HER2 therapy decisions.

There is an unsettled concern that treatment with aromatase inhibitors (AIT) may adversely affect lipid-levels. In light of the improved survival of women with breast cancer and increased risk of atherosclerotic cardiovascular disease in older people, unfavorable effects on lipid-levels may represent a significant health concern for this group of patients. We used linked data from nationwide registries, including a clinical breast cancer database with information about allocated and dispensed AIT. Based on these, we investigated changes in plasma lipid-levels (primary outcome: low-density lipoprotein (LDL)-cholesterol, secondary outcomes: high-density lipoprotein (HDL)-cholesterol, total cholesterol, and triglycerides) following AIT in a nationwide cohort of postmenopausal women with early breast cancer, Denmark, 2009–2020. Included women had at least one LDL-cholesterol measurement before and after breast cancer diagnosis. Exposure was allocated and dispensed AIT as compared with not allocated to and no dispensed AIT. Outcome was the adjusted difference in lipid-level-change (from before to after breast cancer diagnosis) according to AIT. Among 10,461 women, there were 22,693 pre-breast cancer LDL-cholesterol measurements and 42,750 post-breast cancer LDL-cholesterol measurements. Overall, 7919 of the women were exposed to AIT and 2542 women were unexposed. For AIT exposed, the LDL-cholesterol-change was − 0.16 mmol/L (mM), and for unexposed, − 0.15 mM, respectively. The corresponding adjusted difference in LDL-cholesterol change for AIT exposed versus unexposed was − 0.03 mM (95% CI − 0.07 to 0.003). We found similar results in analysis of secondary outcomes. This study does not support the concern that AIT adversely affects lipid-levels.

To report the rates of risk-reducing surgery (RRS) following germline testing for BRCA1/2 (likely) pathogenic variants (BRCApv) and to assess the impact of RRS and BRCA status on survival after surgical treatment for unilateral breast cancer (BC). We identified 7145 women with BC (2000–2017), a BRCA test and median follow-up of 10.8 years from the Danish Breast Cancer Cooperative Group’s clinical database. Distant recurrence-free (DRFS) and overall survival (OS) according to BRCA status were evaluated using the Kaplan–Meier method. Hazard ratios (HR) for BRCApv vs. BRCA wild-type, contralateral risk-reducing mastectomy (CRRM), and risk-reducing bilateral salpingo-oophorectomy (RRBSO), including interaction tests, were estimated using multivariable Cox models. Among BRCA1pv carriers (n = 403), CRRM rates were higher than in BRCA2pv (n = 317) (66

PURPOSE:Tamoxifen is guideline treatment for premenopausal women with estrogen receptor-positive (ER+) breast cancer. Therapeutic efficacy relies partly on tamoxifen biotransformation by CYP2D6, CYP2C19, and CYP3A4 enzymes. We conducted a cohort study to evaluate whether concomitant prescription of drugs that inhibit these enzymes impacted breast cancer recurrence. METHODS:We enrolled 4493 premenopausal women with stage I-III ER+ breast cancer (2002-2011) treated with tamoxifen. We defined time-varying CYP-inhibiting drug exposures as the proportion of overlapping days during the tamoxifen treatment period. We estimated associations of concomitant medication use with recurrence using: (1) Bayesian joint modeling (hazard ratio [HR] and 95% credible intervals [95% CrI]), (2) traditional Cox regression (HR and 95% confidence intervals [95% CI]). RESULTS:During tamoxifen therapy, 13% of the cohort used strong CYP2D6 inhibitors, 31% weak CYP2D6 inhibitors, 37% CYP2C19 inhibitors, and 12% CYP3A4/5 inhibitors. Bayesian joint models showed that women with ≥ 50% overlap between tamoxifen and CYP2D6 inhibitors had increased recurrence risk compared with 0% overlap (HR: 1.24, 95% CrI: 0.96, 1.58). No recurrence association was seen for CYP2C19 inhibitors (≥ 50% vs. 0%, HR = 1.0, 95% CrI: 0.69, 1.40), but traditional Cox models yielded positive associations for CYP2C19 overlap (≥ 50% vs. 0%, HR = 1.45, 95% CI: 1.07, 1.96). With Bayesian joint models, we observed no association between ≥ 50% versus 0% overlap with CYP3A4/5 inhibitors (HR: 0.84, 95% CrI: 0.32, 1.93). CONCLUSIONS:With Bayesian joint modeling, we saw a slight increase in recurrence among CYP2D6-inhibitor users, but no increase among CYP2C19- or CYP3A4-inhibitor users. Results from Cox regression models were less plausible.

Background: The primary purpose of this study was to evaluate the use of less-than-standard surgical therapy in early-stage operable breast cancer nationwide in Denmark. A secondary purpose was to evaluate the use primary endocrine therapy (PET). Methods: We assembled a nationwide, population-based cohort of early-stage operable breast cancer patients registered between 2000 and 2020 in Denmark using the Danish Breast Cancer Group Database, National Patient Registry, and National Pathology Registry. Patients were divided into two groups: those who underwent up-front surgery within 182 days of diagnosis and those who did not, with the latter group further subdivided by use of primary endocrine therapy versus not. We performed Cox regression analyses to assess all-cause mortality risk, adjusting for tumor size, age, comorbidity, estrogen receptor status and year of diagnosis. Results: We identified 84,487 patients with early-stage operable breast cancer. Of these 5,916 patients received less-than-standard therapy, and hereof 2,576 patients received PET. The number of patients for whom surgery was omitted increased from 226 (6.3%) in 2000 to 433 (11.8%) in 2020 and while none of the patients diagnosed in 2000 received PET 296 (8.1%) patients diagnosed in 2020 did. Less-than-standard therapy was associated with a significant higher rate of all-cause mortality. Conclusion: From 2000 to 2020 there was a significant increase in both omittance of surgery and the use of PET among breast cancer patients. Omitted surgery both with or without PET was associated with increased mortality, even after adjusting for tumor size, age, comorbidity, estrogen receptor status and year of diagnosis. Citation Format: Alan Celik, Tobias Berg, Maj-Britt Jensen, Ann Knoop, Bent Ejlertsen. Outcomes following less-than-standard therapy in operable breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-04.

BACKGROUND:Clinical prediction models are increasingly used to guide treatment in patients with early breast cancer. The Danish Breast Cancer Group (DBCG) has developed a prognostic standard mortality rate index (PSI) for prediction of excess mortality based on 5 years of endocrine therapy. In this study, we aimed to evaluate the clinical utility of the PSI. METHODS:In this nationwide, prospective cohort study, we included postmenopausal Danish women aged 50 years or older with invasive oestrogen receptor-positive and HER2-negative resected breast cancer registered in the DBCG clinical database (close to all Danish women newly diagnosed with invasive breast cancer are registered in the national database). All participants were assigned a PSI category. Patients in the PSI 1 category were recommended 5 years of endocrine therapy; patients in PSI 2, 3, or 4 category were recommended endocrine therapy plus adjuvant chemotherapy according to Danish national guidelines. The primary endpoint was standard mortality ratio. Univariable and multivariable analyses for standard mortality ratio, overall survival, and recurrence-free survival were performed applying Kaplan-Meier, cumulative incidence, Poisson regression, and Fine-Gray subdistribution hazards model. FINDINGS:25 027 women diagnosed with breast cancer between Aug 1, 2013, and Dec 31, 2018, and registered with the DBCG clinical database were identified. 8921 of those registered were eligible, assigned a PSI category (6704 [75%] PSI 1, 1300 [15%] PSI 2, 745 [8%] PSI 3, and 172 [2%] PSI 4), and included in the study. 8514 [96%] of 8830 women initiated endocrine therapy and 91 had an unknown therapy status. Adherence at 4·5 years was 67·8% (66·6-69·0) in the PSI 1 group and 72·3% (70·5-74·3) in the PSI 2-4 groups. Crude standard mortality ratio was 0·89 (95% CI 0·85-0·95) with PSI 1, 1·71 (95% CI 1·47-1·97) with PSI 2, and 2·39 (95% CI 1·99-2·88) with PSI 3-4. Compared with patients who completed adjuvant therapy with PSI 1, relative risk (RR) for excess mortality was 1·33 (95% CI 1·01-1·76) for patients with PSI 2 whereas patients with PSI 3-4 retained an excess mortality (RR 2·31, 95% CI 1·74-3·05) even with completed therapy. INTERPRETATION:These data validate the clinical use of the PSI tool for risk adapted treatment allocation. In patients with PSI 1, the omission of chemotherapy was not associated with excess mortality overall and a distinct better outcome was seen in patients with completed endocrine therapy versus those who had not completed. With completed adjuvant therapy, excess mortality was low for patients with PSI 2, whereas patients with PSI 3-4 had high excess mortality, potentially warranting intensified treatment and requiring further investigation. FUNDING:None.

Background: For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. Methods: In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. Findings: 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 43/1000 person-years of follow-up) and 170 two-point MACEs among 6983 patients not allocated to AIT (41/1000 person-years). The adjusted HR was 091 (95% CI 073-114) for patients allocated to AIT versus patients not allocated to AIT. Among 3517 patients with a history of selected cardiovascular disease, we observed 158 two-point MACEs among 2661 patients allocated to AIT (incidence rate 124/1000 person-years) and 50 two-point MACEs (121/1000 person-years) among 856 patients not allocated to AIT (adjusted HR 081 [95% CI 058-115]). Interpretation: Our findings do not support a clinically relevant ischaemic cardiotoxic potential of AIT in patients with early breast cancer and do not support avoiding AIT prescription in patients with early breast cancer.

PURPOSESocial characteristics, including cohabitation/marital status and socioeconomic position (SEP)-education level, employment status, and income-influence breast cancer prognosis. We investigated the impact of these social characteristics on adherence to adjuvant endocrine therapy (AET) from treatment initiation to 5 years after diagnosis.METHODSWe assembled a nationwide, population-based cohort of premenopausal women diagnosed in Denmark with stage I-III, estrogen receptor-positive breast cancer during 2002-2011. We ascertained prediagnostic social characteristics from national registries. AET adherence was based on information from the Danish Breast Cancer Group and operationalized as (1) adherence trajectories (from group-based trajectory modeling) and (2) early discontinuation. We computed odds ratios (ORs) and associated 95% CI to estimate the association of cohabitation and SEP with AET adherence using multinomial and logistic regression models adjusted according to directed acyclic graphs.RESULTSAmong 4,353 patients, we identified three adherence trajectories-high adherence (57%), slow decline (36%), and rapid decline (6.9%). Compared with cohabiting women, those living alone had higher ORs of slow (1.26 [95% CI, 1.08 to 1.46]) or rapid decline (1.66 [95% CI, 1.27 to 2.18]) versus high adherence. The corresponding ORs for women not working versus employed women were 1.22 (95% CI, 1.02 to 1.45) and 1.76 (95% CI, 1.30 to 2.38). For early discontinuation (17%), the ORs were 1.48 (95% CI, 1.23 to 1.78) for living alone and 1.44 (95% CI, 1.17 to 1.78) for women not working.CONCLUSIONAdherence to AET was lower among women living alone or unemployed than cohabiting or employed women, respectively. These women may benefit from support programs to enhance AET adherence.

Continuous CRP and overall survival

INTRODUCTION:Most postmenopausal women with early-stage oestrogen receptor-positive breast cancer are allocated to five years of endocrine therapy. This treatment is not without adverse effects, which may lead to treatment discontinuation. This study aimed to assess compliance with endocrine therapy among postmenopausal women with early-stage oestrogen receptor-positive breast cancer and examine its association with disease-free survival. METHODS:This study retrospectively identified a cohort of 360 postmenopausal women diagnosed in the period from 1 January 2015 to 31 December 2017 at Rigshospitalet, Copenhagen, Denmark, with early-stage oestrogen receptor-positive breast cancer in the clinical database of the Danish Breast Cancer Group. Kaplan-Meier was used to estimate compliance and disease-free survival. RESULTS:A total of 346 patients receiving endocrine therapy were included, 240 were compliant, and 106 were non-compliant. The median follow-up was 6.5 years (95% confidence interval (CI): 6.4-6.7 years). The compliance at 4.5 years was 68.8% (95% CI: 64.1-74.0%). Disease-free survival was significantly higher for the compliant group (adjusted HR = 2.29; 95% CI: 1.34-3.91). CONCLUSIONS:We found a low compliance at 4.5 years and most discontinuations were due to adverse effects. The study provides evidence that low compliance with endocrine therapy had a negative impact on disease-free survival. FUNDING:The study was funded by the Danish Cancer Society. TRIAL REGISTRATION:The study was approved by the research overview of the Capital of Denmark and the Center for Health.

Background: Primary metastatic breast cancer (pMBC) accounts for 5–10% of annual breast cancers with a median survival of 3–4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented. Material and method: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. Results: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000–2004 to 1,323 patients in 2015–2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography–computed tomography) or CT (computed tomography) with a bone evaluation in 2000–2004 and 65% in 2015–2020. Overall survival (OS) improved from 23 months in 2000–2004 to 33 months in 2015–2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. Interpretation: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.