Publications by authors named "S Borgquist"

137 Publications

Overweight and prognosis in triple-negative breast cancer patients: a systematic review and meta-analysis.

NPJ Breast Cancer 2021 Sep 10;7(1):119. Epub 2021 Sep 10.

Department of Oncology, Aarhus University Hospital/Aarhus University, Aarhus, Denmark.

We conducted a systematic review and meta-analysis investigating the association between overweight and outcome in triple-negative breast cancer (TNBC) patients. We searched PubMed and Embase using variations of the search terms triple-negative breast cancer (population), overweight and/or obesity (exposure), and prognosis (outcome). Based on the World Health Organization guidelines for defining overweight, we included longitudinal observational studies, which utilized survival statistics with hazard ratios (HRs) in our analysis. The included studies measured body mass index at the time of diagnosis of TNBC and reported disease-free survival and/or overall survival. Study quality was assessed with the Newcastle-Ottawa Scale and study data were extracted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, independently by two authors. Random-effects models were used to combine the effect sizes (HRs), and the results were evaluated and adjusted for possible publication bias. Thirteen studies of 8,944 TNBC patients were included. The meta-analysis showed that overweight was associated with both shorter disease-free survival (HR = 1.26; 95%CI: 1.09-1.46) and shorter overall survival (HR = 1.29; 95%CI: 1.11c1.51) compared to normal-weight. Additionally, our Bayesian meta-analyses suggest that overweight individuals are 7.4 and 9.9 times more likely to have shorter disease-free survival and overall survival, respectively. In conclusion, the available data suggest that overweight is associated with shorter disease-free and overall survival among TNBC patients. The results should be interpreted with caution due to possible publication bias.
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http://dx.doi.org/10.1038/s41523-021-00325-6DOI Listing
September 2021

CYP2D6 genotype predicts tamoxifen discontinuation and drug response: a secondary analysis of the KARISMA trial.

Ann Oncol 2021 Oct 18;32(10):1286-1293. Epub 2021 Jul 18.

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

Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change.

Patients And Methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers.

Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were -0.8 cm, -4.5 cm, -4.1 cm, and -8.0 cm respectively.

Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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http://dx.doi.org/10.1016/j.annonc.2021.07.005DOI Listing
October 2021

Serum zinc and dietary intake of zinc in relation to risk of different breast cancer subgroups and serum levels as a marker of intake: a prospective nested case-control study.

Breast Cancer Res Treat 2021 Sep 5;189(2):571-583. Epub 2021 Jul 5.

Department of Surgery, Skåne University Hospital Malmö, Lund University, 20501, Malmö, Sweden.

Purpose: Zinc has been suggested to be protective against breast cancer, but the evidence remains inconclusive. One reason for inconsistent findings in previous studies may be that zinc only influences the risk of developing certain subtypes of breast cancer. Our study is the first study assessing zinc levels in relation to the risk of different breast cancer subgroups, defined by their tumor characteristics. In addition, we analyze serum zinc as a marker of dietary intake.

Methods: The Malmö Diet and Cancer Study is a population-based cohort study that took place 1991-1996 in Malmö, Sweden. Until end of follow-up, 31 December 2013, 1186 incident cases were identified and matched to an equal number of controls. Odds ratios (ORs) for breast cancer, and having a certain tumor characteristic, were estimated in quartiles of baseline serum zinc and zinc intake and adjusted for potential confounders.

Results: No associations were found between zinc, measured in serum or diet pre-diagnostically, and breast cancer risk. The adjusted OR for breast cancer in serum zinc Q4 compared to Q1 was 1.09 (0.85-1.41) and in zinc intake Q4 versus Q1 was 0.97 (0.77-1.23). Moreover, there were no clear associations between zinc and any breast cancer characteristics. The kappa value, 0.025 (P = 0.022), showed poor agreement between serum zinc and zinc intake.

Conclusion: Our findings indicate that there is no clear association between zinc and overall breast cancer risk or risk of different breast cancer subgroups. Finally, our results suggest that serum zinc is a poor marker of zinc intake.
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http://dx.doi.org/10.1007/s10549-021-06318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357733PMC
September 2021

Predicting pathological axillary lymph node status with ultrasound following neoadjuvant therapy for breast cancer.

Breast Cancer Res Treat 2021 Aug 12;189(1):131-144. Epub 2021 Jun 12.

Division of Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden.

Purpose: High-performing imaging and predictive markers are warranted to minimize surgical overtreatment of the axilla in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Here we have investigated whether axillary ultrasound (AUS) could identify axillary lymph node (ALN) metastasis (ALNM) pre-NACT and post-NACT for BC. The association of tumor, AUS features and mammographic density (MD) with axillary-pathological complete response (axillary-pCR) post-NACT was also assessed.

Methods: The NeoDense-study cohort (N = 202, NACT during 2014-2019), constituted a pre-NACT cohort, whereas patients whom had a cytology verified ALNM pre-NACT and an axillary dissection performed (N = 114) defined a post-NACT cohort. AUS characteristics were prospectively collected pre- and post-NACT. The diagnostic accuracy of AUS was evaluated and stratified by histological subtype and body mass index (BMI). Predictors of axillary-pCR were analyzed, including MD, using simple and multivariable logistic regression models.

Results: AUS demonstrated superior performance for prediction of ALNM pre-NACT in comparison to post-NACT, as reflected by the positive predictive value (PPV) 0.94 (95% CI 0.89-0.97) and PPV 0.76 (95% CI 0.62-0.87), respectively. We found no difference in AUS performance according to neither BMI nor histological subtype. Independent predictors of axillary-pCR were: premenopausal status, ER-negativity, HER2-overexpression, and high MD.

Conclusion: Baseline AUS could, to a large extent, identify ALNM; however, post-NACT, AUS was insufficient to determine remaining ALNM. Thus, our results support the surgical staging of the axilla post-NACT. Baseline tumor biomarkers and patient characteristics were predictive of axillary-pCR. Larger, multicenter studies are needed to evaluate the performance of AUS post-NACT.
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http://dx.doi.org/10.1007/s10549-021-06283-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302508PMC
August 2021

The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study.

Front Oncol 2021 20;11:642768. Epub 2021 May 20.

Division of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, Sweden.

The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including and genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002-2012, was followed until June 30 2019 (median 8.7 years). Tumor-specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhR) and nuclear (AhR) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhR levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER) status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HR 0.42; 95% CI 0.22-0.83). High AhR levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HR 0.40; 95% CI 0.23-0.71) compared to low AhR levels, whereas an almost inverse association was seen in patients with switch-therapy ( =0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators.
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http://dx.doi.org/10.3389/fonc.2021.642768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174786PMC
May 2021
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