uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Holmberg, Lars
Alternative names
Publications (10 of 209) Show all publications
Crawley, D., Chamberlain, F., Garmo, H., Rudman, S., Zethelius, B., Holmberg, L., . . . Van Hemelrijck, M. (2018). A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus. ecancermedicalscience, 12, Article ID 802.
Open this publication in new window or tab >>A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus
Show others...
2018 (English)In: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 12, article id 802Article, review/survey (Refereed) Published
Abstract [en]

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

Keywords
type two diabetes, prostate cancer, review
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-350200 (URN)10.3332/ecancer.2018.802 (DOI)000423854500001 ()29456619 (PubMedID)
Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Wärnberg, F., Garmo, H., Folkvaljon, Y., Holmberg, L., Karlsson, P., Sandelin, K., . . . Bremer, T. (2018). Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS). Paper presented at San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX. Cancer Research, 78(4)
Open this publication in new window or tab >>Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)
Show others...
2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 4Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351602 (URN)10.1158/1538-7445.SABCS17-GS5-08 (DOI)000425489400036 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Wos title: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)

Supplement: S

Meeting Abstract: GS5-08

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-05-29
Pettersson, A., Robinson, D., Garmo, H., Holmberg, L. & Stattin, P. (2018). Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.. Annals of Oncology, 29(2), 377-385
Open this publication in new window or tab >>Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.
Show others...
2018 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no 2, p. 377-385Article in journal (Refereed) Published
Abstract [en]

Background: Old age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity.

Patients and methods: We conducted a nation-wide cohort study including 121,392 Swedish men aged 55-95 years in Prostate Cancer data Base Sweden (PCBaSe) 3.0 diagnosed with prostate cancer in 1998-2012 and followed for prostate cancer death through 2014. Data were available on age, stage, grade, PSA-level, mode of detection, comorbidity, educational level and primary treatment. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CIs).

Results: With increasing age at diagnosis, men had more comorbidity, fewer PSA detected cancers, more advanced cancers and were less often treated with curative intent. Among men with high-risk or regionally metastatic disease, the proportion of men with unknown M stage was higher among old men versus young men. During a follow-up of 751,000 person-years, 23,649 men died of prostate cancer. In multivariable Cox-regression analyses stratified by treatment, old age at diagnosis was associated with poorer prognosis among men treated with deferred treatment (HRage 85+ vs. 60-64: 7.19; 95% CI: 5.61-9.20), androgen deprivation therapy (HRage 85+ vs. 60-64: 1.72; 95% CI: 1.61-1.84) or radical prostatectomy (HRage 75+ vs. 60-64: 2.20; 95% CI: 1.01-4.77), but not radiotherapy (HRage 75+ vs. 60-64: 1.08; 95% CI: 0.76-1.53).

Conclusion: Our findings argue against a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic work-up and subsequent curative treatment.

Keywords
Age at diagnosis, Cohort study, Prognosis, Prostate cancer, Treatment
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-336231 (URN)10.1093/annonc/mdx742 (DOI)29161337 (PubMedID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2018-04-26Bibliographically approved
Bosco, C., Garmo, H., Hammar, N., Walldius, G., Jungner, I., Malmström, H., . . . Van Hemelrijck, M. (2018). Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospective study in the Swedish AMORIS cohort. BMC Cancer, 18, Article ID 205.
Open this publication in new window or tab >>Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospective study in the Swedish AMORIS cohort
Show others...
2018 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 18, article id 205Article in journal (Refereed) Published
Abstract [en]

Background: Improvements in detection and treatment of prostate cancer (PCa) translate into more men living with PCa, who are therefore potentially at risk of a secondly diagnosed primary tumour (SDPTs). Little is known about potential biochemical mechanisms linking PCa with the occurrence of SDPTs. The current study aims to investigate serum biomarkers of glucose and lipid metabolism and gamma-glutamyl transferase (GGT) measured prior to PCa diagnosis and their association with the occurrence of SDPTS.

Methods: From the Swedish AMORIS cohort, we selected all men diagnosed with PCa between 1996 and 2011, with at least one of the five biomarkers of interest (glucose, fructosamine, triglycerides, total cholesterol (TC), GGT) measured on average 16 years before PCa diagnosis (n = 10,791). Multivariate Cox proportional hazards models were used to determine hazard ratios (HR) for risk of SDPTs (overall and subtypes) by levels of the five biomarkers. Effect modification of treatment was assessed.

Results: 811 SDPTS were diagnosed during a median follow-up time of 5 years. Elevated levels of triglycerides (HR: 1.37, 95% CI: 1.17-1.60), TC (HR: 1.22, 95% CI: 1.04-1.42) and GGT (HR: 1.32, 95% CI: 1.02-1.71) were associated with an increased risk of SDPTs. Risk of SDPTs subtypes varied by biomarkers.

Conclusion: Elevated levels of biomarkers of lipid metabolism and GGT measured prior to PCa diagnosis were associated with an increased risk of SDPTs, suggesting a potential common biochemical background for development of PCa and SDPTs.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2018
Keywords
Prostate cancer, Second primary tumours, Triglycerides, Gamma-glutamyl transferase, Glucose, Total cholesterol
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-349350 (URN)10.1186/s12885-018-4111-5 (DOI)000425517700006 ()29463235 (PubMedID)
Funder
Swedish Cancer SocietyForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-05-02Bibliographically approved
Åström, L., Grusell, E., Sandin, F., Turesson, I. & Holmberg, L. (2018). Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer. Radiotherapy and Oncology, Article ID S0167-8140(17)32780-9.
Open this publication in new window or tab >>Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer
Show others...
2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, article id S0167-8140(17)32780-9Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) has optimal prerequisites in radiotherapy of prostate cancer (PC) with a conformal dose distribution and high doses per fraction giving a biological dose escalation. We report the outcome after HDR-BT and external beam radiotherapy (EBRT) after 20 years of experience.

MATERIAL AND METHODS: The study includes 623 patients, median age of 66 years, treated from 1995 to 2008 and a median follow up of 11 years (range 2-266 months). Androgen deprivation therapy was given to 429 patients (69%). The HDR-BT was given with two 10 Gy fractions and the EBRT with 2 Gy fractions to 50 Gy.

RESULTS: The 10-year PC-specific survival was 100%, 92%, 91%, and 75% for low-, intermediate-, high- and very high-risk patients respectively, and the 10-year probability of PSA relapse was 0%, 21%, 33%, and 65% respectively. The 10-year actuarial prevalence for ≥grade 2 GU- and GI-toxicities were 28% and 12% respectively and for ≥grade 3, 4% and 1% respectively. Urethral stricture was the most frequent GU complication with a 10-year actuarial incidence of 10%. Treatment without dose constraints for the urethra conferred a higher incidence 18%, compared to 5% after 2003 (p < 0.001). Sixteen patients experienced grade 4 GU toxicity, of which 13 were treated before 2003. No grade 4 rectal toxicity was seen.

CONCLUSION: The combination of EBRT and HDR-BT with adequate dose constraints to risk organs provides satisfactory long-term tumour control even in high-risk patients. GI toxicity stabilised but GU toxicity progressed during the 10-year follow up.

Keywords
Brachytherapy, High dose rate, Prostate cancer, Radiotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-347411 (URN)10.1016/j.radonc.2017.12.025 (DOI)29496280 (PubMedID)
Available from: 2018-03-31 Created: 2018-03-31 Last updated: 2018-05-08Bibliographically approved
Fredholm, H., Magnusson, K., Lindstrom, L. S., Tobin, N. P., Lindman, H., Bergh, J., . . . Fredriksson, I. (2017). Breast cancer in young women and prognosis: How important are proliferation markers?. European Journal of Cancer, 84, 278-289
Open this publication in new window or tab >>Breast cancer in young women and prognosis: How important are proliferation markers?
Show others...
2017 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 84, p. 278-289Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Breast cancer, Young, Age, Subtype, Luminal, Progesterone receptor, Ki-67, Cyclin, Prognosis, Population-based
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-336293 (URN)10.1016/j.ejca.2017.07.044 (DOI)000411333300032 ()28844016 (PubMedID)
Available from: 2018-01-23 Created: 2018-01-23 Last updated: 2018-01-23Bibliographically approved
Yiu, A., Van Hemelrijck, M., Garmo, H., Holmberg, L., Malmström, H., Lambe, M., . . . Wulaningsih, W. (2017). Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study. OncoTarget, 8(26), 42332-42342
Open this publication in new window or tab >>Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study
Show others...
2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 26, p. 42332-42342Article in journal (Refereed) Published
Abstract [en]

Objectives: Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort.

Results: A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women.

Materials and Methods: We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers.

Conclusions: Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.

Keywords
uric acid, cancer, prospective study
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-332205 (URN)10.18632/oncotarget.16198 (DOI)000405493400049 ()28418841 (PubMedID)
Available from: 2017-10-26 Created: 2017-10-26 Last updated: 2017-11-29Bibliographically approved
Häggström, C., Liedberg, F., Hagberg, O., Aljabery, F., Ströck, V., Hosseini, A., . . . Holmberg, L. (2017). Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe). BMJ Open, 7(9), Article ID e016606.
Open this publication in new window or tab >>Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)
Show others...
2017 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e016606Article in journal (Refereed) Published
Abstract [en]

Purpose: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).

Participants: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.

Findings to date: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.

Future plans: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-337759 (URN)10.1136/bmjopen-2017-016606 (DOI)000412650700144 ()28963292 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/472
Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-01-12Bibliographically approved
Lawler, K., Papouli, E., Naceur-Lombardelli, C., Mera, A., Ougham, K., Tutt, A., . . . Purushotham, A. (2017). Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study. Breast Cancer Research, 19, Article ID 113.
Open this publication in new window or tab >>Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study
Show others...
2017 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 19, article id 113Article in journal (Refereed) Published
Abstract [en]

Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.

Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated.

Results: Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort.

Conclusion: This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Breast cancer, Metasynchronous metastases, Gene expression pattern
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337331 (URN)10.1186/s13058-017-0881-y (DOI)000412892700001 ()29029636 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 259881
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-01-03Bibliographically approved
Grönberg, M., Ahlin, C., Naeser, Y., Tiensuu Janson, E., Holmberg, L. & Fjällskog, M.-L. (2017). Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer. PLoS ONE, 12(4), Article ID e0176059.
Open this publication in new window or tab >>Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer
Show others...
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176059Article in journal (Refereed) Published
Abstract [en]

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size <= 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

Keywords
Hormone releasing hormone, food intake, cell-lines, cyclin-A, expression, obestatin, stomach, identification, secretion, receptor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-322807 (URN)10.1371/journal.pone.0176059 (DOI)000399875200066 ()28419141 (PubMedID)
Available from: 2017-09-13 Created: 2017-09-13 Last updated: 2017-11-29Bibliographically approved
Organisations

Search in DiVA

Show all publications