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Background: Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive., Methods: We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors., Results: Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR 1-SD 1.25, 95% CI 1.07-1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR 1-SD 1.41, 95% CI 1.18-1.69) and BC-specific mortality (HR 1-SD 1.31, 95% CI 1.03-1.66), (P Heterogeneity (pre/postmenopausal)  < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR 1-SD 1.19, 95% CI 1.02-1.40 and HR 1-SD 1.28, 95% CI 1.06-1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR 1-SD 1.35, 95% CI 1.10-1.65 and HR 1-SD 1.42 95% CI 1.08-1.86), while TNF-α was associated with all-cause mortality in HER2- (HR 1-SD 1.31, 95% CI 1.07-1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR 1-SD 1.30, 95% CI 1.07-1.58)., Conclusions: Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality., (© 2024. The Author(s).)

Background: Preclinical studies have shown both pro- and antineoplastic effects of antihistamines. Here, we evaluated the effect of H1 antihistamines on contralateral breast cancer (CBC) risk, and whether cationic amphiphilic (CAD) antihistamines could increase the sensitivity to chemotherapy., Methods: From the Danish Breast Cancer Group clinical database, we identified all women aged ≥20 years with a first-time diagnosis of breast cancer during 1996-2012. Information on drug use, CBC and potential confounding factors was retrieved from nationwide registries. Using Cox proportional hazard regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with H1-antihistamine use., Results: We identified 52,723 patients with breast cancer with a total of 310,583 person-years of follow-up. Among them, 1444 patients developed a new primary tumour in the contralateral breast. Post-diagnosis use of H1 antihistamines (≥2 prescriptions) was not strongly associated with CBC risk (HR 1.08, 95% CI: 0.90-1.31) compared with non-use (<2 prescriptions). Use of CAD antihistamines among patients receiving chemotherapy was not associated with a decrease in CBC risk., Conclusions: Taken together, our findings do not suggest any association of H1-antihistamine use with CBC development.

Background: Statins have demonstrated antineoplastic effects in breast cancer cell lines, particularly in oestrogen receptor (ER)-negative cell lines. However, epidemiological studies have not supported a preventive effect of statin use against breast cancer. Therefore, we examined the association between statin use and contralateral breast cancer (CBC) risk among women with breast cancer., Methods: We identified 52,723 women with non-metastatic breast cancer during 1996-2012 from the Danish Breast Cancer Group database. We defined time-varying post-diagnosis statin use as minimum two prescriptions lagged by 1 year. Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with statin use., Results: Statin use was associated with a lower CBC risk (HR = 0.88; 95% CI = 0.73-1.05). The inverse association was strongest for long-term use overall (HR = 0.64; 95% CI = 0.43-0.96), although the HR specifically for long-term consistent use and high-intensity use approached unity. Among ER-negative breast cancer patients, statin use was associated with a CBC risk reduction (HR = 0.67; 95% CI = 0.45-1.00)., Conclusions: We found some indication that statins reduce the risk of CBC. Further evaluations are needed to disentangle the equivocal results for long-term use and to establish if ER-negative breast cancer patients may benefit most from statin use.

Background: Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height., Methods: From the prospective Danish cohort 'Diet, Cancer and Health', 23 864 postmenopausal women enrolled during 1993-1997 were followed for a diagnosis of breast cancer in the Danish Cancer Registry through 2009., Results: The incidence rate ratios for breast cancer were 1.11 (95% CI=1.06-1.16) for each 5 cm increase in total height and 1.09 (95% CI=1.01-1.17) and 1.14 (95% CI=1.04-1.25) for each 5 cm increase in leg length and sitting height, respectively. There was no statistical significant difference between the associations for leg length and sitting height (P=0.47)., Conclusion: Leg length does not seem to be more strongly associated with breast cancer among postmenopausal women than sitting height.

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

Although venous thromboembolism (VTE) is common in patients with cancer, it is not known if it is associated with risk of a second malignancy. Using the Danish Cancer Registry and National Registry of Patients, we studied a population-based cohort of 6285 patients with cancer who had an episode of VTE. The risk of a second cancer was compared with that among 30 713 cancer patients without VTE, matched for age, sex, cancer site and year of diagnosis. Overall, the relative risk for a second cancer diagnosis was 1.3 (95% confidence interval (CI) 1.1-1.4). However, the excess risk varied with the time from the initial cancer diagnosis to the thrombotic event. If the thrombotic episode occurred within the first year, the relative risk for a second cancer was 1.0 (95% CI 0.9-1.3), but if the VTE occurred more than 1 year after the initial cancer, the overall relative risk for a second cancer was 1.4 (95% CI 1.2-1.7), with strong associations for cancers of the digestive organs, ovary and prostate. The association between VTE and subsequent incident cancer extends to patients who already have had a cancer diagnosis.

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.

Numerous studies and meta-analyses have shown that hormone replacement therapy (HRT) for menopausal symptoms increases the risk of developing breast cancer, estimated to be 2.3% for each year of use. The influence of different oestrogen-progestin regimens has still not been fully evaluated. Using longitudinal data from the population-based prescription database of the county of North Jutland, Denmark, and the Danish Cancer Registry, we examined the risk of developing breast cancer in relation to HRT in a cohort of 78,380 women aged 40-67 years from 1989 to 2002. A total of 1462 cases of breast cancer were identified during a mean follow-up of 10 years. Use of HRT did not increase the risk of breast cancer in women aged 40-49 years. Restricting the cohort to 48,812 women aged 50 years or more at entry, of whom 15 631 were HRT users, we found an increased risk associated with current use of HRT (relative risk 1.61, 95% confidence interval 1.38-1.88). The risk increased with increasing duration of use and decreased with time since last HRT prescription, reaching unity after 5 years. No material risk difference was observed among the various HRT-regimens. This population-based cohort study provides further confirmation that HRT increases the risk of developing breast cancer in women aged 50 years or more.

An international multicentre study of first and second primary neoplasms associated with male breast cancer was carried out by pooling data from 13 cancer registries. Among a total of 3409 men with primary breast cancer, 426 (12.5%) developed a second neoplasia; other than breast cancer, a 34% overall excess risk of second primary neoplasia, affecting the small intestine (standardised incidence ratio, 4.95, 95% confidence interval, 1.35-12.7), rectum (1.78, 1.20-2.54), pancreas (1.93, 1.14-3.05), skin (nonmelanoma, 1.65, 1.16-2.29), prostate (1.61, 1.34-1.93) and lymphohaematopoietic system (1.63, 1.12-2.29). A total of 225 male breast cancers was recorded after cancers other than breast cancer, but an increase was found only after lymphohaematopoietic neoplasms. BRCA2 (and to some extent BRCA1) mutations may explain the findings for pancreatic and prostate cancers. Increases at other sites may be related to unknown factors or to chance. This large study shows that the risks for second discordant tumours after male breast cancer pose only a moderate excess risk.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

We examined the risk of cancer and survival in a cohort of patients hospitalised with herpes zoster between 1977 and 1996, drawn from the Danish National Registry of Patients. Through linkage with the Danish Cancer Registry, we compared the observed number of cancers with the expected number on the basis of national age-, gender-, and site-specific incidence rates. The survival of herpes zoster patients with cancer was compared with that of non-herpes zoster patients with cancer. Among the 10 588 patients hospitalised with herpes zoster whom we identified, 1427 cancers were observed compared with 1239 expected (relative risk=1.2, 95% confidence interval 1.1-1.2). The risk was substantially elevated during the first year of follow-up, mainly for haematological cancer. Patients with cancer within 1 year of follow-up had a higher prevalence of distant metastases than controls, although the mortality was similar. For those with haematological cancer, however, the mortality was higher for herpes zoster patients than for controls. Haematological cancer following hospitalisation for herpes zoster has a poorer prognosis than in non-herpes zoster patients.

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172 057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0-1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6-0.9) and 0.6 (95% CI 0.4-0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4-1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4-1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1-1.6), 1.4 (95% CI 0.9-2.1), and 1.6 (95% CI 1.3-2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.

Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53,811 children of more than 36,000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968-1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0-19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0-2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9-1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia.

To examine the association between gallstones and cholecystectomy, we conducted a nationwide population-based cohort study in Denmark. Patients with a discharge diagnosis of gallstones from 1977 to 1989 were identified from the Danish National Registry of Patients and followed up for cancer occurrence until death or the end of 1993 by record linkage to the Danish Cancer Registry. Included in the cohort were 60 176 patients, with 471 450 person-years of follow-up. Cancer risks were estimated by standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) stratified by years of follow-up and by cholecystectomy status. Among patients without cholecystectomy, the risks at 5 or more years of follow-up were significantly elevated for cancers of liver (SIR = 2.0, CI = 1.2-3.1) and gallbladder (SIR = 2.7, CI = 1.5-4.4) and near unity for cancers of extrahepatic bile duct (SIR = 1.1), ampulla of Vater (SIR = 1.0) and pancreas (SIR = 1.1). The excess risk of liver cancer was seen only among patients with a history of hepatic disease. Among cholecystectomy patients, the risks at 5 or more years of follow-up declined for cancers of liver (SIR = 1.1) and extrahepatic bile duct (SIR = 0.7), but were elevated for cancers of ampulla of Vater (SIR = 2.0, CI = 1.0-3.7) and pancreas (SIR = 1.3, CI = 1.1-1.6). These findings confirm that gallstone disease increases the risk of gallbladder cancer, whereas cholecystectomy appears to increase the risk of cancers of ampulla of Vater and pancreas. Further research is needed to clarify the carcinogenic risks associated with gallstones and cholecystectomy and to define the mechanisms involved.

A cohort of 5072 patients with pernicious anaemia was identified in the Danish Hospital Discharge Register from 1977 to 1989 and, through linkage to the Danish Cancer Registry, the occurrence of cancer in the cohort was determined up to 1991. Observed numbers of cancer cases during 1-15 years of follow-up were compared with expected numbers based on national incidence rates. Besides the well-established increased risk for stomach cancer, the analysis also revealed a 2-fold increase in the relative risk for cancer of the buccal cavity and pharynx among pernicious anaemia patients in accordance with previous studies; previously reported elevated risks for other digestive tract cancers were not confirmed. There was a non-significantly increased risk for lymphatic and haematological malignancy but the risk tended to disappear after 5 years of follow-up, indicating a possible selection bias. Decreased risks for cervical cancer and non-melanoma skin cancer were also seen.